Since the discovery of HIV, scientists have made major inroads in understanding modes of transmission, infectivity, and pathogenicity. Knowledge about the characteristics and behavior of this human retrovirus and its complex mechanisms of immunopathogenesis has helped to develop targeted therapeutic interventions and vaccine strategies. Sophisticated techniques have been and are being developed to diagnose infection, to monitor immune decline, to monitor response to therapy and disease progression, and to accurately detect and diagnose opportunistic diseases. Therapeutic alternatives, especially the nucleoside analogue antiretroviral drugs, have been tested, approved, and are providing benefit to many who are HIV-infected. Much has been learned about the complexities of caring for HIV-infected persons, how to keep them disease-free longer, and how to manage their symptoms more effectively. In addition, the development of new knowledge from HIV-related research also has helped to clarify aspects of the human immune response, behavioral interventions, public health strategies, and social and ethical approaches that contribute to the understanding and management of other diseases and health conditions. Healthcare professionals will continue to play a major and significant role in preventing the spread of HIV infection and in caring for those who are infected or affected by HIV. As the demographics of HIV infection evolve, both in the United States and around the world, it is clear that all healthcare professionals in all practice settings will be involved to some extent with HIV infection. To be effective and provide compassionate care, adequate and up-to-date information about transmission, prevention, diagnosis, treatment, and care of HIV-infected individuals must be obtained by all healthcare professionals. They must feel comfortable with this knowledge in order to provide care, educate patients and others, and fulfill their professional obligations without undue fear or anxiety.
This course is designed to fulfill the Washington requirement for HIV/AIDS education.
This course is designed for all nurses, physicians, and allied healthcare professionals in Washington involved in the care of patients with HIV/AIDS.
NetCE is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. NetCE is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. NetCE has been approved by NBCC as an Approved Continuing Education Provider, ACEP No. 6361. Programs that do not qualify for NBCC credit are clearly identified. NetCE is solely responsible for all aspects of the programs. NetCE, #1092, is approved as a provider for social work continuing education by the Association of Social Work Boards (ASWB) www.aswb.org through the Approved Continuing Education (ACE) Program. NetCE maintains responsibility for the program. ASWB Approval Period: 03/13/2016 to 03/13/2019. Social workers should contact their regulatory board to determine course approval for continuing education credits. NetCE is accredited by the International Association for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.
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This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency. This course is designed to fulfill the Washington requirement for HIV/AIDS education. Participants will receive 7 hours of continuing education for completing this course.
In view of the already existing crisis in healthcare in the United States, the problems associated with providing the necessary care for persons with HIV infection or AIDS are significant. The purpose of this course is to address those problems in the discussion of epidemiology, organism characteristics, pathophysiology, transmission, clinical manifestations, complications, treatment advancements, prevention, ethical and legal aspects of care, and workplace concerns.
Upon completion of this course, you should be able to:
- Discuss the background and significance of the AIDS epidemic, including geographic patterns of transmission.
- Discuss the characteristics of the infecting organism and the various HIV tests available.
- Describe the transmission and natural history of HIV infection, including risk behaviors and routes of contagion.
- Describe the treatments available in the care of patients with HIV, including antiretroviral medications used in patient care.
- Discuss the impact of the virus on women living with HIV infection.
- Review the transmission of HIV to the infant and child, and discuss care of these infected children.
- Summarize issues unique to older persons with HIV infection.
Jane C. Norman, RN, MSN, CNE, PhD, received her undergraduate education at the University of Tennessee, Knoxville campus. There she completed a double major in Sociology and English. She completed an Associate of Science in Nursing at the University of Tennessee, Nashville campus and began her nursing career at Vanderbilt University Medical Center. Jane received her Masters in Medical-Surgical Nursing from Vanderbilt University. In 1978, she took her first faculty position and served as program director for an associate degree program. In 1982, she received her PhD in Higher Education Administration from Peabody College of Vanderbilt University. In 1998, Dr. Norman took a position at Tennessee State University. There she has achieved tenure and full professor status. She is a member of Sigma Theta Tau National Nursing Honors Society. In 2005, she began her current position as Director of the Masters of Science in Nursing Program.
John M. Leonard, MD, Emeritus Professor of Medicine, Vanderbilt University School of Medicine. Dr. Leonard completed his post-graduate clinical training at the Yale and Vanderbilt University Medical Centers, and then joined the Vanderbilt faculty in 1974. He has served as director of educational programs for the Department of Medicine and was the Residency Program Director from 1981 to 2003. Dr. Leonard's clinical experience includes an active practice of general internal medicine and an inpatient consulting practice of infectious diseases.
Contributing faculty, Jane C. Norman, RN, MSN, CNE, PhD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.
Contributing faculty, John M. Leonard, MD, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.
Ronald Runciman, MD
Alice Yick Flanagan, PhD, MSW
The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.
The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.
Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.
It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.
- NATURAL HISTORY AND CLASSIFICATION OF HIV INFECTION
- HIV TESTING
- TRANSMISSION OF HIV
- MANAGEMENT OF HIV INFECTION
- WOMEN LIVING WITH HIV INFECTION
- INFANTS AND CHILDREN WITH HIV
- OLDER PEOPLE WITH HIV
- AIDS PREVENTION
- HIV/AIDS REPORTING
- WASHINGTON STATUTES
- Works Cited
- Evidence-Based Practice Recommendations Citations
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#94731: HIV/AIDS: Epidemic Update for Washington
The amount that has been learned and written about human immunodeficiency virus (HIV) infection and disease and its influence on individuals and society is staggering. Since the first recognized case of HIV in the United States more than 30 years ago, researchers have made major inroads in understanding modes of transmission, infectivity, and pathogenicity. Knowledge about the characteristics and behavior of this human retrovirus and its complex mechanisms of immunopathogenesis has helped to develop targeted therapeutic interventions and vaccine strategies. Sophisticated techniques have been and are being developed to diagnose infection, monitor immune decline, monitor response to therapy and disease progression, and accurately detect and diagnose opportunistic diseases.
The immune deficiency characterizing HIV disease is manifested by markedly depressed T lymphocyte functioning, with a reduction of helper T cells (T4), impaired killer T cell activities, and increased suppressor T cells (T8). By selectively invading and infecting T cells, the virus damages the very cell whose function it is to orchestrate the identification and destruction of the virus as antigen. Other cells with the same molecular makeup might also become infected. Eventually, the individual's supply of functional T cells becomes depleted. In a person with a competent immune system, the number of T4 cells ranges from 600–1,200 per mm3, whereas the patient with HIV might have 0–500 per mm3 T4 cells .
Clinical manifestations of HIV are generally related to opportunistic infections preying on an impaired immune system. These diseases include Pneumocystis carinii pneumonia (PCP) and tuberculosis. The HIV patient commonly succumbs to uncontrollable infection, becoming increasingly debilitated, feverishly ill, malnourished, and often in pain. Lymphadenopathy, pulmonary infiltrates, wasting syndrome, and neurologic abnormalities, such as dementia, tremors, and encephalitis, contribute to the debilitated state. Because HIV travels from cell to cell rather than through the bloodstream, it is usually not susceptible to circulating antibodies of the body's remaining immune system B cells. To date, there is no predictable course of curative treatment .
Therapeutic alternatives, especially the nucleoside analogue antiretroviral drugs, have been tested, approved, and are providing benefit to many who are HIV-infected. Much has been learned about the complexities of caring for HIV-infected persons, how to keep them disease-free longer, and how to manage their symptoms more effectively. In addition, the development of new knowledge from HIV-related research has also helped to clarify aspects of the human immune response, behavioral interventions, public health strategies, and social and ethical approaches that contribute to the understanding and management of other diseases and health conditions.
The epidemiology of HIV infections is presented as it appears in Africa, Asia, Europe, and the United States. Analysis reveals that the HIV pandemic continues to escalate throughout developing countries compared to a notable stabilization in new cases and fatalities in some developed countries. The established healthcare community became aware of the illness that has since become known as acquired immune deficiency syndrome (AIDS) in 1981. The tasks of slowing the HIV pandemic and decreasing the mortality rate are being accomplished by efforts such as diligent treatment of sexually transmitted infections (STIs), increased condom distribution, and utilization of needle exchange programs. In order to further decrease HIV transmission, there are increased efforts to strengthen public health infrastructures, support HIV/STI prevention programs, introduce microbicide, use inexpensive antiretroviral drug therapy for treatment and prevention of transmission, and improve educational campaigns [1,44].
Two human immunodeficiency viruses, HIV-1 and HIV-2, have been identified and both cause AIDS. Researchers in America and England have traced the ancestry of the HIV-1 virus to two strains found in African red-capped mangabeys and greater spot-nosed monkeys. The strains most likely combined in chimpanzees that ate both types of monkeys, resulting in the chimpanzees developing simian immunodeficiency virus (SIV). Chimpanzees then transmitted the virus to humans, as early as 1930. Genetic studies suggest that the lower monkeys first became infected with SIV at least 100,000 years ago . HIV-2 is believed to be endemic in West Africa. Several well-documented cases of HIV-2 infection have been reported in Europeans and among West Africans residing abroad. Between 1996 and 2009, there were a total of 242 reported cases of HIV-2 in the United States, the majority of which were associated with immigration from, travel to, or a sexual partner from West Africa . Differences in the global spread are attributed to differences in transmissibility and duration of infectiousness .
Many countries owe acquisition of HIV infection in their population to sexual transmission or contact with American blood products that were exported before the 1985 HIV screening procedures.
In 1988, the World Health Organization (WHO) established three broad, but distinct, geographic patterns of AIDS transmission, based on worldwide epidemiological studies . It is important to note that, due to a number of factors, these transmission patterns are evolving.
According to these definitions, in pattern I, typical of industrialized countries with large numbers of reported cases, most cases occurred among men who have sex with men (MSM) and among urban injection drug users (IDUs). A smaller percentage of cases are attributed to heterosexual transmission, but this percentage is increasing significantly. Transmission from exposure to HIV-contaminated blood or blood products occurred between the late 1970s and 1985, but this has since been largely controlled through routine blood screening procedures .
Pattern II, which was mainly found in areas of central, eastern, and southern Africa and in some Caribbean countries, is comprised of cases occurring mostly among heterosexuals. MSM and IDU transmission either does not occur or occurs at a very low rate. Transmission through contaminated blood and blood products remains a significant problem .
Pattern III is observed in areas of eastern Europe, the Middle East, Asia, and most of the Pacific basin. HIV appeared to have been introduced to these areas since the mid-1980s. When the WHO originally described this pattern, only small numbers of cases had been reported. Generally, cases had occurred among those who have traveled to endemic areas or who had sexual contact with individuals from endemic areas. A small number of cases had been reported due to receipt of imported HIV-contaminated blood . However, the percentage of HIV-infected population in Asia, particularly in the south and east areas, is increasing. Although transmission patterns vary geographically, the highest risk groups appear to be MSM, IDUs, and female sex workers and their clients . Several areas within this pattern group, such as Russia, China, and India, have been identified as "second wave countries" and are considered at risk for a future pandemic .
According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), an estimated 35.3 million individuals worldwide were living with HIV/AIDS in 2012, approximately half of whom were women . Eastern Europe (particularly the Russian Federation), Central Asia, the Middle East, and Northern Africa have the fastest growing epidemic . It is important to note that despite increases in certain geographic areas and demographic groups, overall, the rate of new infections is declining. This is due, in part, to lower prices for anti-AIDS drugs and implementation of prevention programs . Africa is still the hardest hit area, with 71% of all HIV-infected persons living in sub-Saharan Africa in 2012 . In 2003, the U.S. government approved the purchase of generic drugs to fight the disease in Africa. In that same year, the President's Emergency Plan for AIDS Relief (PEPFAR) was introduced and implemented . PEPFAR was reauthorized in 2008 and 2013, with more than $50 billion in funds to HIV/AIDS and to address additional health issues, including malaria, tuberculosis, maternal health, and clean water .
As of 2012, an estimated 1.3 million individuals were living with HIV/AIDS in North America . The CDC estimates that approximately 20% of these individuals are unaware of their infection . To compound the problem, only 51% of individuals aware of their infection receive ongoing care. Approximately 72% of all individuals infected with HIV remain untested, without treatment, or both . Unfortunately, this poses a risk both for those who are infected and for others.
Many changes in the progression of the HIV/AIDS epidemic should be considered. Since the first reported cases of HIV in 1981 in the United States, the epidemic continues to vary a great deal between regions, states, and even communities. Populations that are affected by HIV are also shifting. In addition to individuals traditionally considered to be high-risk (e.g., MSM or IDUs), new groups have been identified as being at greater risk. For example, in the beginning stages of the HIV/AIDS epidemic in the United States, white people were chiefly impacted. However, the epidemic now greatly affects racial and ethnic minorities, particularly black Americans, who represent nearly half of all new diagnoses in the United States . Women also have a higher risk of infection. More than half of HIV infections that result from heterosexual contact occur in women.
One should keep in mind when reviewing HIV/AIDS trends that the widespread use of antiretroviral therapy (ART) has resulted in fewer deaths and longer survival . As of 2013, the Centers for Disease Control and Prevention (CDC) report several trends in the HIV/AIDS epidemic :
By region, 40% of persons living with AIDS reside in the South, 30% in the Northeast, 20% in the West, and 10% in the Midwest.
By race/ethnicity, 42% are black, 37.9% white, 17.4% Hispanic, 1.5% are multiple race, and less than 1% are American Indian/Alaska Native or Asian/Pacific Islander.
By gender, 80% of adults and adolescents living with AIDS are male.
The CDC has published guidelines for medical professionals to integrate HIV prevention into the regular medical care of those living with HIV. The three major components of the recommendation are :
Screening for HIV transmission risk behaviors and STIs
Providing brief, behavioral risk-reduction interventions in the office setting and referring selected patients for additional prevention interventions and other related services
Facilitating notification and counseling for sex and needle-sharing partners of infected persons
The CDC, in partnership with other U.S. Department of Health and Human Services agencies and other government and non-government agencies, also launched the initiative Advancing HIV Prevention: New Strategies for a Changing Epidemic . This initiative was a response to increases in HIV infections.
The CDC has also developed a method to better measure the rate of HIV infections in the United States. The Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS) has allowed the CDC to more accurately monitor the number of new HIV infections in the United States, which in turn should facilitate targeted prevention in those populations most in need [18,19]. STARHS consists of two tests to determine both seropositivity and how recently the infection was contracted.
As of 2013, an estimated 11,500 to 12,700 Washington residents are living with HIV, with the vast majority of cases occurring in King County (7,200 to 8,000) and Pierce County (1,100 to 2,000) . Each year, there are approximately 500 to 600 new cases within the state. The demographics of HIV/AIDS infection in Washington reflect its unique population. The majority of persons living with HIV/AIDS in Washington are white (66%) and male (86%); however, the rate of white males contracting the disease has been decreasing over the past few decades . In 2012, 48% of new cases were among people of color, compared to 32% in 1998. The rates of infection among black persons who are U.S.-born (33 per 100,000/year) and foreign-born (92 per 100,000/year) are approximately 2.3 and 6.4 times that of whites, respectively, although the absolute number of cases is far fewer . Infection rates have also increased significantly among Hispanic men and Asians/Pacific Islanders. While the overall number of persons living with HIV/AIDS in Washington decreased significantly in the 1990s, it has been relatively constant since 2000.
HIV is a retrovirus, carrying genetic information in ribonucleic acid (RNA) rather than in deoxyribonucleic acid (DNA). It infects the T lymphocyte by binding to it at the CD4 receptor site and inserting its RNA into the cell. Through an enzyme called reverse transcriptase, the HIV RNA is converted to DNA. When the T cell is activated to reproduce, its genetic information is now programmed to produce more HIV, at the expense of normal T cell function.
Clinical latency, sometimes referred to as the "window" period, is the asymptomatic period of time before the body recognizes the virus and programs antibodies. The exact time that antibodies develop varies, but it is longer in HIV than in many other infectious organisms. The clinical latency period for blood-transmitted HIV infection is thought to be 4 to 7 weeks, and antibody formation after infection through sexual contact is thought to occur 6 to 14 months after the introduction of the virus. The prolonged latency period effectively reduces the accuracy and immediacy of host identification. One of the theories concerning this prolonged latency period is that HIV invades T cells and, in effect, sequesters itself from view of the body's surveillance system, meanwhile multiplying anomalous T cells that are ineffective for purposes of immunity .
HIV is a protracted infection that passes through several stages and, if untreated, carries an 80% mortality rate at 10 years. The initial event, reported in 50% to 90% of patients, is an acute retroviral syndrome characterized as an infectious, mononucleosis-like illness. Symptoms include fever, sore throat, malaise, rash, diarrhea, lymphadenopathy, mucocutaneous ulcerations, and weight loss averaging 10 pounds. A variety of neurologic syndromes, including encephalitis, may occur.
The illness begins 1 to 3 weeks after viral transmission and is self-limited, with an average duration of 2 to 3 weeks. Laboratory abnormalities include lymphopenia, atypical lymphocytosis, and a decreased CD4 cell count. During this early phase, HIV antibody tests are negative, and the diagnosis rests on the demonstration of HIV P24 antigen or, preferably, quantitative plasma HIV RNA. Concentrations of HIV RNA in the blood (viral load) are high during the acute syndrome.
Following the host immune response there is seroconversion with positive serology, and the viral load decreases considerably, reaching a relatively stable level at about 6 months. At this juncture, the degree of viral load will dictate the subsequent course. Patients having high viral concentrations, 105 copies/mL or higher, will have a relatively rapid course. The prolonged and progressive infection of target lymphocytes results in an annual average decrease in CD4 count of about 50/mm3.
Early-stage HIV infection is characterized by an almost complete absence of symptoms and relatively normal laboratory studies. However, there is a gradual decline in CD4 count with positive serologic and virologic studies indicating past infection and persistent viral activity. Patients may be subclassified based on a laboratory evaluation that includes a complete blood count with differential white blood cell count and a platelet count. Immunologic tests, such as the T-lymphocyte helper and suppressor cell counts, are also an important part of the overall evaluation. Patients with test results that are within normal limits and those who have not yet had complete evaluations should be differentiated from patients whose test results are consistent with HIV-associated defects, lymphopenia, thrombocytopenia, and a decreased number of T4 lymphocytes . The duration of this asymptomatic stage is variable depending on the level of viremia as measured by HIV RNA and is affected by ART.
Patients may have persistent generalized lymphadenopathy (PGL) without pain or further disease findings. PGL is defined as palpable lymph node enlargement of 1 cm or greater, at two or more extra-inguinal sites that persists for more than 3 months in the absence of a concurrent illness or condition other than HIV infection to explain the findings. In some cases, lymphadenopathy regresses as HIV disease advances, probably because the architecture of the lymph node is gradually destroyed .
Symptomatic infection can be expected to supervene after the CD4 count has decreased to less than 200/mm3 as this represents the stage of severe immunodeficiency. The CDC defines late stage HIV infection as AIDS on the basis of two criteria: characteristic AIDS-defining illness such as PCP, central nervous system (CNS) toxoplasmosis, or other opportunistic infections or tumors (Kaposi's sarcoma). A variety of clinical syndromes may supervene at this juncture including dementia, peripheral neuropathy, wasting syndrome, and chronic diarrhea. In the United States, the most common AIDS-defining opportunistic diseases are :
The initial evaluation of the patient with HIV should include assessment of the oral cavity. Several oral manifestations may occur with HIV infection, with increasing incidence associated with decreasing CD4 counts. The majority of patients with AIDS will experience at least one oral complication during the course of the disease, the most common of which are candidiasis, oral hairy leukoplakia (caused by reactivation of the Epstein-Barr virus), HIV-associated periodontal disease (including necrotizing gingivitis or periodontitis), and Kaposi's sarcoma. Salivary gland disease can also occur in HIV/AIDS patients and can cause unilateral or bilateral enlargement of the salivary glands, most commonly the parotid glands. Xerostomia can result from this glandular involvement and may be exacerbated by the use of antiviral medications . These oral manifestations are difficult to treat, and some will be refractory to any approaches. Accurate diagnosis, early and aggressive treatment, and close monitoring are necessary.
In the absence of ART, the average survival is approximately 3.5 years after the patient's CD4 count has reached 200/mm3 and 1.5 years for the patient who has developed an AIDS-defining disease. The natural history has been dramatically altered by ART, especially since the introduction of protease inhibitors and non-nucleoside reverse transcriptase inhibitors in 1996.
For individuals who acquired AIDS through injection drug use, co-infection with hepatitis C virus is present in 80% of cases. Approximately 25% of all HIV-infected persons in the United States are also infected with hepatitis C virus; 10% are co-infected with hepatitis B virus . Hepatitis C virus is one of the most common causes of chronic liver disease in the United States, and for those individuals co-infected with hepatitis C virus and HIV, liver damage progresses more rapidly. The CDC, the Infectious Diseases Society of America (IDSA), and the National Institutes of Health guidelines recommend that all HIV-infected persons be screened for hepatitis C virus infection .
Intervention and treatment of opportunistic diseases and infections is dependent on the ability of the health provider to diagnose, monitor, and educate patients at risk. The main challenge to health providers is choosing those interventions that will alleviate suffering and morbidity, while not exceeding the financial and technical capabilities of the health system .
Several tests are available to screen for HIV. There are various ways by which these tests function: detection of the antibody, identification of antigens, detection/monitoring of viral nucleic acids, or rendering an estimate of T-lymphocytes (cell phenotyping). Tests used to detect antibodies are the most common and effective way of identifying HIV infection and can be further broken down into two categories :
Screening Tests: Intended to determine all individuals infected with HIV; produces few false-negative results
Supplemental/Confirmatory Tests: Intended to determine all individuals who have positive screening tests, but are not infected (i.e., negates a false-positive), produces few false-positive results
Both types of tests are highly sensitive. Together, they can accurately assess the existence of HIV in blood supply and supplement clinical diagnosis.
The enzyme-linked immunosorbent assay (ELISA), a test originally developed to screen the nation's blood supply, is also common and effective for detecting the presence of HIV antibodies. ELISA is quick, easy to perform, and extremely sensitive; however, its high sensitivity causes a higher rate of false-positive results. There can also be false-negative results with ELISA if the test is conducted before the individual develops antibodies or if the individual is too ill to produce antibodies. When the ELISA test is positive, it should be repeated. If positive again, a supplemental/confirmatory test, such as the Western Blot test, is then used to confirm the presence of HIV antibodies. The Western Blot test uses the more expensive process of electrophoresis; therefore, it is typically used only as a confirmatory test .
The OraQuick HIV rapid test detects the presence of antibodies to HIV-1 and produces results within 20 minutes from a single drop of blood. Positive results require confirmation by Western Blot or immunofluorescence assays . Several other rapid HIV antibody screening tests have been approved (Table 1) [22,81]. The benefits of these tests are that they produce results quickly and are cost-effective.
FDA-APPROVED RAPID HIV ANTIBODY SCREENING TESTS
|Test||FDA Approval||Specimen Type||Approved for HIV-2 Detection|
|OraQuick ADVANCE Rapid HIV-1/2 Antibody Test||November 2002||Oral fluid, whole blood (fingerstick or venipuncture), or plasma||Yes|
|Uni-Gold Recombigen HIV||December 2003||Whole blood (fingerstick or venipuncture), serum, or plasma specimens||No|
|Reveal G-3 Rapid HIV-1 Antibody Test||April 2003||Serum and plasma||No|
|MultiSpot HIV-1/HIV-2 Rapid Test||November 2004||Serum and plasma||Yes–differentiates HIV-1 from HIV-2|
|Clearview HIV 1/2 STAT-PAK||May 2006||Whole blood (fingerstick or venipuncture), serum, or plasma specimens||Yes|
|Clearview COMPLETE HIV 1/2||May 2006||Whole blood (fingerstick or venipuncture), serum, or plasma specimens||Yes|
|INSTI HIV-1 Antibody Test||November 2010||Whole blood (fingerstick or venipuncture), serum, or plasma specimens||Seeking postmarket approval|
|Alere Determine HIV-1/2 Ag/Ab Combo||August 2013||Whole blood (fingerstick or venipuncture), serum, or plasma specimens||Yes|
Screening for the antibody is helpful only to the extent that individuals who have been exposed to HIV can be identified. However, not all of these individuals actually carry the virus, nor will all of them show signs of illness. Therefore, several situations are possible:
Exposure: An individual may be exposed to the virus but neither carry it nor contract the disease.
Carrier: The individual may carry the virus with the capability of infecting others without accompanying signs and symptoms.
Terminal Disease: The individual may be infectious, symptomatic, and terminal. HIV disease becomes AIDS when the immune system is so damaged that the number of CD4+ T-lymphocyte cells is less than 200 per mm3 or an opportunistic infection occurs.
It is thought that carriers of the virus who test positive for the antibody can remain as carriers for years with the virus in a dormant state. Although approximately one-third of those who now test positive for the disease eventually will begin to show clinical manifestations, it is thought by some investigators that the percentage of those who go on to develop the disease will eventually approach 100% .
As discussed, in addition to these conventional tests there is also a method for determining length of infection . According to the CDC, the BED HIV-1 Capture EIA Assay is based on the observation that the ratio of anti-HIV IgG to total IgG increases with time after HIV infection . If a confirmed HIV-1 positive specimen is reactive on the standard sensitive EIA and has a normalized optical density of <0.8 on the BED assay, the patient is considered recently infected. This test is used in the United States for surveillance purposes.
Informed consent should be obtained from each person being tested. Each individual should be fully aware of the limitations of the HIV-antibody test regarding HIV infection and the development of AIDS. The test and its meaning, the reason for ordering the test, and its potential adverse consequences should be understood. The consent also includes information about how the test information will be used. In the state of Washington, no person may undergo HIV testing without the person's consent except in cases of incompetence, double-blinded seroprevalence studies, and/or when the department of labor and industries determines that it is relevant .
There have been court cases that have centered on testing without consent; therefore, it is imperative that all healthcare providers follow the procedures concerning consent to test. HIV testing may only be done with patient's consent. Informed consent includes: documentation of consent on the chart, pre- and post-test counseling and referrals. The physician ordering the test is required to tell the patient if the result is positive; offer counseling and appropriate referrals.
An individual's ability and prerogative to make decisions about treatment is now seen as a vital expression of autonomy and is a prerequisite to participation in treatment or interventions. Autonomy, individualism, and self-determination are belief systems that are highly valued in Western societies, especially in the United States. Autonomy may be categorized into two groups: first-order autonomy and second-order autonomy . First-order autonomy is what Westerners espouse and value: self-determination and autonomy in decision making. Second-order autonomy, however, is prevalent in collectivistic societies where decision making is group-oriented and takes into account another decision-maker who is accorded authority and respect . For example, in many Asian cultures, particularly if the family system is based on a patriarchal authority system, a male elder or leader who is regarded as the primary decision-maker is key in this process of informed consent.
The process of informed consent entails the explicit communication of information in order for the individual to make a decision. Again, Western cultures value explicit information, which is centered on American consumerism; believing in having choices and being able to exercise choices in purchases extends to healthcare. However, some cultures believe that language and information also shape reality . In other words, explicit information, particularly if it is bad information, will affect the course of reality.
A signature is required on most Western informed consent forms to represent understanding and agreement on the part of the individual involved. Yet, this might be viewed as violation of social etiquette in some cultures. In some cultures (for example, Egypt), signatures are usually associated with major life events and legal matters. Therefore, requiring a signature outside these circumstances would imply a lack of trust, particularly when verbal consent has been given .
Furthermore, consent forms often contain technical and legal jargon that may be overwhelming to the native English speaking individual, but can be much more daunting for immigrants who may not be English proficient or familiar with various legal concepts. For some immigrants who have experienced political persecution in their homelands, asking for a signature on a consent form that contains foreign legal and technical terms can potentially place them at risk for secondary traumatization, as some were persecuted, tortured, and forced to sign documents in their homelands .
This cultural dissonance can be a challenge to many general healthcare and mental health practitioners. Cultural experts are highly recommended for consultations to assist in the interpretation and navigation of the complex web of cultural interactions.
It is important the healthcare professionals protect patients' rights to privacy and confidentiality and offer anonymous testing when appropriate. In Washington, local health officers are required to :
Ensure anonymous HIV testing is reasonably available
Make HIV testing, AIDS counseling, and pretest and post-test counseling available for voluntary, mandatory, and anonymous testing and counseling
Make information on anonymous HIV testing, AIDS counseling, and pretest and post-test counseling available
Use identifying information on HIV- infected individuals provided only:
For purposes of contacting the HIV-positive individual to provide test results and post-test counseling
To contact persons who have experienced substantial exposure, including sex and injection equipment-sharing partners, and spouses
To link with other name-based public health disease registries when doing so will improve ability to provide needed care services and counseling and disease prevention
Destroy documentation of referral information containing identities and identifying information on HIV-infected individuals and at-risk partners of those individuals immediately after notifying partners or within three months, whichever occurs first
According to the Washington Department of Health, sharing the results of any sexually transmitted infection (STI) testing is restricted . The exchange of medical information among healthcare providers and within facilities in order to provide healthcare services to the patient is permitted, and the results of HIV testing may be released to the following recipients:
The subject of the test
A person with a release of information from the tested person
Health officials in accordance with reporting requirements for diagnosed STIs
Facilities that collect blood, tissue, or semen
Health officials, first responders, or victims of sexual assault who petition the court to order testing
A person allowed access to information by a court order
Local law enforcement if health officers have exhausted procedures to stop behaviors that present a danger to the health of the public
Exposed persons who are notified because releasing the identity of the infected person is necessary
Payers of health claims
Agencies or guardians responsible for children younger than 14 years of age with an STI
However, HIV testing results should be released to approved parties with the following warning: "This information has been disclosed to you from records whose confidentiality is protected by state law. State law prohibits you from making any further disclosure of it without the specific written consent of the person to whom it pertains, or as otherwise permitted by state law. A general authorization for the release of medical or other information is NOT sufficient for this purpose" .
Transmission of HIV results from intimate contact with blood and body secretions, excluding saliva and tears. The most common modes of transmission are sexual contact, administration of contaminated blood and blood products, contaminated needles, and mother-to-fetus. Blood transfusions of whole blood, packed cells, and fresh frozen plasma are most unlikely to be the cause of transmission with the more sophisticated crossmatching and antibody screening measures; individuals needing specific blood components (such as factor VIII and frequent plasma replacement) are more at risk .
On the basis of newly reported cases, the transmission categories are :
Male-to-male sexual contact
MSM who inject drugs
High-risk heterosexual contact
No reported risk category
HIV has been isolated from blood, seminal fluid, pre-ejaculate, vaginal secretions, urine, cerebrospinal fluid, saliva, tears, and breast milk of infected individuals. Whether HIV infects spermatozoa is controversial. Reports of the removal of infected cells from semen, allowing artificial insemination without seroconversion, support the idea that spermatozoa are not infected. No cases of HIV infection have been traced to saliva or tears .
The virus is found in greater concentration in semen than in vaginal fluids, leading to a hypothesis that male-to-female transmission could occur more easily than female-to-male. Sexual behavior that involves exposure to blood is likely to increase transmission risks. Transmission could occur through contact with infected bowel epithelial cells in anal intercourse in addition to access to the bloodstream through breaks in the rectal mucosa.
Although all HIV-seropositive people are potentially infectious, there is widespread variation in the seropositivity and seroconversion of their sexual partners. Factors that could explain this variability include differences in sexual practices and numbers of sexual contacts, susceptibility of the partner, differences in viral strains, changing degrees of infectiousness of the HIV-infected person over time, co-factors that enhance or limit transmission, genetic resistance, or a combination of these factors.
Posing the highest risk of infection is unprotected anal receptive intercourse, followed by unprotected vaginal intercourse. Risk is reduced through the use of latex condoms. For the wearer, latex condoms provide a mechanical barrier limiting penile exposure to infectious cervical, vaginal, vulvar, or rectal secretions or lesions. Likewise, the partner is protected from infectious pre-ejaculate, semen, and penile lesions. Oil-based lubricants may make latex condoms ineffective and should not be used. Water-soluble lubricants are considered safe. Natural membrane condoms (made from lamb cecum) contain small pores and do not block HIV passage.
It is estimated that latex condom efficacy in the prevention of HIV transmission is approximately 85% . Although abstinence from sexual contact is the sole way to absolutely prevent transmission, using a latex condom to prevent transmission of HIV is more than 10,000 times safer than engaging in unprotected sex . Sexual activity in a mutually monogamous relationship in which neither partner is HIV-infected and no other risk factors are present is considered safe .
The phenomenon of men who identify publicly as heterosexual and generally have committed relationships with women, but who also engage in sexual activity with other men, termed being on the "down low" (DL), may be a transmission bridge to heterosexual women. In a 2005 study, researchers surveyed 328 MSM in 12 cities and found that 43% of black men, 26% of Hispanic men, and 7% of white men reported being on the down low . It is important to note that men on the down low are not the only MSM who report having sexual contact with women. In a larger study of 5,000 HIV-positive MSM, 22% of gay-identified black MSM and 61% of bisexual-identified black MSM reported having had sex with a woman in the past five years .
However, a 2009 study of 1,151 black MSM in New York City and Philadelphia challenged the association of down low identity with increased HIV risk behavior . Of the respondents, 31% identified as down low, and of those, 11% identified as heterosexual, 25% identified as homosexual, and the remainder presumably identified as bisexual. Down low MSM were found to engage in fewer instances of unprotected receptive anal sex compared to non-down low MSM and were also less likely to be HIV positive. The authors concluded that predicting risk based on actual sexual behaviors is much more accurate than trying to associate a particular identity with HIV risk for female sex partners of MSM, as male sexual identity does not predict the frequency of sexual contact with women.
Numerous studies have demonstrated that oral sex can result in the transmission of HIV and other STIs. While the risk of HIV transmission through oral sex is much smaller than the risk from anal or vaginal sex, there are several co-factors that can increase this risk, including oral ulcers, bleeding gums, genital sores, and the presence of other STIs. Prevention includes the use of latex condoms, a natural rubber latex sheet, plastic food wrap, a condom cut into a sheet, or a dental dam, all of which serve as a physical barrier to transmission .
It has been estimated that an HIV-infected drop of human blood contains 1 to 100 live virus particles. In comparison, a drop infected with hepatitis B virus has 100 million to 1 billion organisms. Even so, HIV is transmitted via blood, primarily through sharing of contaminated needles among IDUs and, rarely, through blood transfusion. Transmission of HIV-1 has occurred after transfusion of the following components: whole blood, packed red blood cells (including washed and buffy coat poor), fresh frozen plasma, cryoprecipitate, platelets, and plasma-derived products, depending on the production process.
With the implementation of a donor screening program of the nation's blood supply in 1985 and advances in the treatment of donated blood products, blood transfusion is now even safer; the current risk of transmission of AIDS through this route is estimated to be 1 in 225,000. A somewhat higher estimate of 1 in 40,000 to 1 in 60,000 is reported from areas that have a high prevalence of HIV-1 infection. It is possible that before blood screening implementation, more than 12,000 people were infected. A large percentage of hemophiliacs acquired HIV in this manner. Donor screening, HIV testing, and heat treatment of the clotting factor have greatly reduced the risks. To further decrease the possibility of HIV transmission through transfusion of blood and blood products, patients scheduled to undergo elective surgery are increasingly advised to make predeposited blood donations for intraoperative autotransfusion.
To date, screening tests cannot detect either recently HIV-1-infected people who have not yet developed antibody (the "window period") or HIV antibody-negative patients who have AIDS. Donating procedures include an interview for risk factors and the ability of the potential donor to exclude their blood from being used. Very few transfusion-related cases of HIV infection have been reported in the United States since 1992, when all U.S. blood centers began to test donations for antibodies to both HIV-1 and HIV-2 . Clinicians should recommend HIV antibody testing for all people transfused between January 1978 and March 1985, although the likelihood of new cases from this transmission category is low .
Transmission of HIV among injecting drug users occurs primarily through contamination of injection paraphernalia with infected blood. The risk of sustaining HIV infection from a needle stick with infected blood is approximately 1 in 300. Behavior such as needle sharing, "booting" the injection with blood, and performing frequent injections increases the risk. Cocaine use (by injection or smoking) is associated with a higher prevalence of HIV infection. This may in part be attributed to the exchange of cocaine for sex. Sharing of equipment is common due to legal and financial restrictions and cultural norms. Geographically, the rate of infection varies; 80% of New York City addict needle sharers are infected, as opposed to lower rates in other metropolitan area clusters. Secondary transmission occurs to children and sexual partners. Preventative strategies include drug treatment, onsite medical care in a drug treatment program, recruitment of "street" outreach workers for intensive drug and sex "risk reduction" educational campaigns, teaching addicts to sterilize their equipment between use, the free provision or exchange of sterile injection equipment (as allowed by law), distribution of condoms and bleach to clean drug use equipment, or a combination of these interventions .
Health professionals should stress the following messages when they counsel IDUs :
The best way for you to prevent HIV and hepatitis B and C virus transmission is to NOT inject drugs.
Entering substance abuse treatment can help you reduce or stop injecting. This will lower your chances of infection.
Get vaccinated against hepatitis A and hepatitis B. You can prevent these kinds of viral hepatitis if you get vaccinated.
If you cannot or will not stop injecting, you should:
Use a new, sterile syringe obtained from a reliable source to prepare and divide drugs for each injection.
Never reuse or share syringes, water, cookers, or cottons.
Use sterile water to prepare drugs each time, or at least clean water from a reliable source.
Keep everything as clean as possible when injecting.
If you cannot use a new, sterile syringe and clean equipment each time, then disinfecting with bleach may be better than doing nothing at all:
Fill the syringe with clean water and shake or tap. Squirt out the water and throw it away. Repeat until you do not see any blood in the syringe.
Completely fill the syringe with fresh, full-strength household bleach. Keep it in the syringe for 30 seconds or more. Squirt it out and throw the bleach away.
Fill the syringe with clean water and shake or tap. Squirt out the water and throw it away.
If you do not have any bleach, use clean water to vigorously flush out the syringe. Fill the syringe with water and shake or tap it. Squirt out the water and throw it away. Repeat several times.
It is important to note that a disinfected syringe is not a sterile syringe. The best option is always to use a new, sterile syringe with every injection.
In the absence of prophylactic treatment, approximately 30% to 50% of children born to HIV-infected mothers will contract HIV infection. HIV is transmitted to infants by transplacental spread from mother to fetus in utero, during parturition, or through breastfeeding after birth. Because infants have underdeveloped natural resistance systems, they are highly susceptible to many infections, including HIV. Both uninfected and infected infants have been born to mothers who have previously borne an infected infant. Studies have dramatically shown the beneficial effect of treating pregnant women and newborns with Zidovudine (ZDV) to prevent transmission to the child, resulting in declines in the incidence of perinatally acquired AIDS . Standard screening of all pregnant women is necessary to reduce transmission of HIV to infants.
Worldwide, perinatal transmission accounts for most HIV infections among children. In the United States in 2010, 143 infants were born with HIV infection, down from more than 1,700 in the mid-1990s . In all, perinatal transmission has markedly decreased, by more than 80%, since 1991. This dramatic decrease is mainly attributed to the use of ART . Other strategies for reducing perinatally acquired HIV infection have included preventing HIV infection among women and, for HIV-infected women, avoiding pregnancy or refraining from breastfeeding. On February 21, 1994, the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Child Health and Human Development (NICHD) announced preliminary results from a randomized, multicenter, double-blind clinical trial of ZDV to prevent HIV transmission from mothers to their infants. This report summarizes the interim results of that trial, which indicate effectiveness of ZDV for prevention of perinatal transmission. Based on these interim findings, NIAID accepted the recommendation of an independent data and safety monitoring board to terminate enrollment into the trial and to offer ZDV to women in the group who had received the placebo but had not yet delivered and to their infants younger than 6 weeks of age .
Transmission due to occupational exposure of healthcare workers has occurred in needlestick accidents and blood splashes to the mucous membranes. Needlestick is the most common route. Thousands of healthcare personnel who were so exposed have been studied, and only 57 cases of well-documented infection have been reported in the United States (24 of which were nurses) . The risk of infection through this route is low, and every effort should be made to decrease the exposure rate. Educational efforts, implementation of engineering controls in needled and sharp-edged medical devices, the use of hard plastic needle disposal units where these devices are most frequently used, and the development of procedural details to avoid blood and body fluid contact have greatly reduced the exposure rate. Healthcare personnel must apply universal precautions, as discussed in the Occupational Safety and Health Administration (OSHA) Bloodborne Pathogens standard regulations, to all activities to avoid contact with human fluids .
All body fluids should be considered potentially infectious. Contaminated needles or other sharps should not be bent, recapped or removed, unless specifically required by a particular medical or dental procedure. All healthcare professionals should have access to and use personal protective equipment, such as gloves, gowns, face shields, masks, eye protection, and ventilation devices, to limit exposure to potentially infectious fluids. OSHA standards require that single-use gloves be worn when contact with blood or other potentially infectious substance, including mucous membranes, can be reasonably anticipated .
This section, Postexposure Prophylaxis, is from the Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis .
The definitions of HCP and occupational exposures are unchanged from those used in 2001 and 2005. The term HCP refers to all paid and unpaid persons working in healthcare settings who have the potential for exposure to infectious materials including body substances (e.g., blood, tissue, and specific body fluids), contaminated medical supplies and equipment, or contaminated environmental surfaces. HCP might include, but are not limited to, emergency medical service personnel, dental personnel, laboratory personnel, autopsy personnel, nurses, nursing assistants, physicians, technicians, therapists, pharmacists, students and trainees, contractual staff not employed by the healthcare facility, and persons not directly involved in patient care but potentially exposed to blood and body fluids (e.g., clerical, dietary, housekeeping, security, maintenance, and volunteer personnel). The same principles of exposure management could be applied to other workers with potential for occupational exposure to blood and body fluids in other settings.
An exposure that might place HCP at risk for HIV infection is defined as a percutaneous injury (e.g., a needlestick or cut with a sharp object) or contact of mucous membrane or nonintact skin (e.g., exposed skin that is chapped, abraded, or afflicted with dermatitis) with blood, tissue, or other body fluids that are potentially infectious. In addition to blood and visibly bloody body fluids, semen and vaginal secretions also are considered potentially infectious. Although semen and vaginal secretions have been implicated in the sexual transmission of HIV, they have not been implicated in occupational transmission from patients to HCP. The following fluids also are considered potentially infectious: cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, and amniotic fluid. The risk for transmission of HIV infection from these fluids is unknown; the potential risk to HCP from occupational exposures has not been assessed by epidemiologic studies in healthcare settings. Feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious unless they are visibly bloody.
Any direct contact (i.e., contact without barrier protection) to concentrated virus in a research laboratory or production facility requires clinical evaluation. For human bites, clinical evaluation must include the possibility that both the person bitten and the person who inflicted the bite were exposed to bloodborne pathogens. Transmission of HIV infection by this route has been reported rarely, but not after an occupational exposure.
The recommendations in this section apply to situations in which a healthcare provider has been exposed to a source person who either has, or there is a reasonable suspicion of, HIV infection. These recommendations reflect expert opinion and are based on limited data regarding safety, tolerability, efficacy, and toxicity of PEP. If PEP is offered and taken and the source is later determined to be HIV-negative, PEP should be discontinued and no further HIV follow-up testing is indicated for the exposed provider. Because the great majority of occupational HIV exposures do not result in transmission of HIV, the potential benefits and risks of PEP (including the potential for severe toxicity and drug interactions, such as may occur with oral contraceptives, H2-receptor antagonists, and proton pump inhibitors, among many other agents) must be considered carefully when prescribing PEP. Because of the complexity of selecting HIV PEP regimens, whenever possible, these recommendations should be implemented in consultation with persons who have expertise in the administration of antiretroviral therapy and who are knowledgeable about HIV transmission. Reevaluation of exposed HCP is recommended within 72 hours post-exposure, especially as additional information about the exposure or source person becomes available.
A regimen containing three (or more) antiretroviral drugs is now recommended routinely for all occupational exposures to HIV (Table 2). Examples of recommended PEP regimens include those consisting of a dual nucleoside reverse transcriptase inhibitor (NRTI) backbone plus an integrase strand transfer inhibitor (INSTI), a protease inhibitor (boosted with ritonavir), or a non-nucleoside reverse transcriptase inhibitor. Other antiretroviral drug combinations may be indicated for specific cases (e.g., an exposure to a source patient harboring drug-resistant HIV), but should only be prescribed after consultation with an expert in the use of antiretroviral agents.
HIV POSTEXPOSURE PROPHYLAXIS REGIMENS
|Raltegravir (Isentress; RAL) 400 mg PO twice daily plus Truvada,1 PO once daily [Tenofovir DF (Viread; TDF) 300 mg + emtricitabine (Emtriva; FTC) 200 mg]|
|Alternative Regimens (May combine one drug or drug pair from the left column with one pair of nucleoside/nucleotide reverse transcriptase inhibitors from the right column.)|
|A complete fixed-dose combination regimen and no additional antiretrovirals are needed: Stribild (elvitegravir, cobicistat, tenofovir DF, emtricitabine)|
|Alternative Agents for Use as PEP only with Expert Consultation|
|Antiretroviral Agents Generally Not Recommended for Use as PEP|
|Antiretroviral Agents Contraindicated as PEP|
|Nevirapine (Viramune; NVP)|
Animal studies have suggested that PEP is most effective when begun as soon as possible after the exposure and that PEP becomes less effective as time from the exposure increases, PEP should be initiated as soon as possible, preferably within hours of exposure. Occupational exposures to HIV should be considered urgent medical concerns and treated immediately. For example, a surgeon who sustains an occupational exposure to HIV while performing a surgical procedure should promptly scrub out of the surgical case, if possible, and seek immediate medical evaluation for the injury and PEP. Additionally, if the HIV status of a source patient for whom the practitioner has a reasonable suspicion of HIV infection is unknown and the practitioner anticipates that hours or days may be required to resolve this issue, antiretroviral medications should be started immediately rather than delayed.
Although animal studies demonstrate that PEP is likely to be less effective when started more than 72 hours postexposure, the interval after which no benefit is gained from PEP for humans is undefined. If initiation of PEP is delayed, the likelihood increases that benefit might not outweigh the risks inherent in taking antiretroviral medications. Initiating therapy after a longer interval (e.g., 1 week) might still be considered for exposures that represent an extremely high risk for transmission. The optimal duration of PEP is unknown; however, duration of treatment has been shown to influence success of PEP in animal models. Because 4 weeks of PEP appeared protective in animal, in vitro, and occupational studies, PEP should be administered for 4 weeks, if tolerated.
The decision to offer HIV PEP to a pregnant or breastfeeding healthcare provider should be based upon the same considerations that apply to any provider who sustains an occupational exposure to HIV. The risk of HIV transmission poses not only a threat to the mother, but also to the fetus and infant, as the risk of mother-to-child HIV transmission is markedly increased during acute HIV infection during pregnancy and breastfeeding. However, unique considerations are associated with the administration of antiretroviral agents to pregnant HCP, and the decision to use antiretroviral drugs during pregnancy should involve both counseling and discussion between the pregnant woman and her healthcare provider(s) regarding the potential risks and benefits of PEP for both the healthcare provider and for her fetus.
The potential risks associated with antiretroviral drug exposure for pregnant women, fetuses, and infants depend on the duration of exposure as well as the number and type of drugs. Information about the use of newer antiretroviral agents, administered as PEP to HIV-uninfected pregnant women, is limited. For reasons including the complexities associated with appropriate counseling about the risks and benefits of PEP, as well as the selection of antiretroviral drugs in pregnant women, expert consultation should be sought in all cases in which antiretroviral medications are prescribed to pregnant HCP for PEP.
HCP who have experienced occupational exposure to HIV should receive follow-up counseling, postexposure testing, and medical evaluation regardless of whether they take PEP. Greater emphasis is placed upon the importance of follow-up of HCP on HIV PEP within 72 hours of exposure and improving follow-up care provided to exposed HCP. Careful attention to follow-up evaluation within 72 hours of exposure can: 1) provide another (and perhaps less anxiety-ridden) opportunity to allow the exposed HCP to ask questions and for the counselor to make certain that the exposed HCP has a clear understanding of the risks for infection and the risks and benefits of PEP, 2) ensure that continued treatment with PEP is indicated, 3) increase adherence to HIV PEP regimens, 4) manage associated symptoms and side effects more effectively, 5) provide an early opportunity for ancillary medications or regimen changes, 6) improve detection of serious adverse effects, and 7) improve the likelihood of follow-up serologic testing for a larger proportion of exposed personnel to detect infection. Closer follow- up should in turn reassure HCP who become anxious after these events. The psychological impact of needlesticks or exposure to blood or body fluid should not be underestimated for HCP. Exposed personnel should be advised to use precautions (e.g., use of barrier contraception, avoid blood or tissue donations, pregnancy, and if possible, breastfeeding) to prevent secondary transmission, especially during the first 6 to 12 weeks postexposure. Providing HCP with psychological counseling should be an essential component of the management and care of exposed HCP.
HIV testing should be used to monitor HCP for seroconversion after occupational HIV exposure. After baseline testing at the time of exposure, follow-up testing should be performed at 6 weeks, 12 weeks, and 6 months after exposure. Use of fourth generation HIV Ag/Ab combination immunoassays allow for earlier detection of HIV infection. If a provider is certain that a fourth generation combination HIV Ag/Ab test is used, HIV follow-up testing could be concluded earlier than 6 months after exposure. In this instance, an alternative follow-up testing schedule could be used (e.g., baseline testing, 6 weeks, and then concluded at 4 months after the exposure). Extended HIV follow-up (e.g., for 12 months) is recommended for HCP who become infected with HCV after exposure to a source who is co-infected with HIV and HCV. Whether extended follow-up is indicated in other circumstances (e.g., exposure to a source co-infected with HIV and HCV in the absence of HCV seroconversion or for exposed persons with a medical history suggesting an impaired ability to mount an antibody response to acute infection) is unknown.
In 2005, the CDC published guidelines for the recommendation of PEP for nonoccupational exposures. This section is taken from Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV in the United States as reported in the CDC's Morbidity and Mortality Weekly Report, January 21, 2005.
Accumulated data from animal and human clinical and observational studies demonstrate that ART initiated as soon as possible within 48 to 72 hours of sexual, injection-drug use, and other substantial nonoccupational HIV exposure and continued for 28 days might reduce the likelihood of transmission. Because of these findings, the Department of Health and Human Services (DHHS) recommends the prompt initiation of nPEP with ART when persons seek care within 72 hours after exposure, the source is known to be HIV infected, and the exposure event presents a substantial risk for transmission. When the HIV status of the source is not known and the patient seeks care within 72 hours after exposure, DHHS does not recommend for or against nPEP but encourages clinicians and patients to weigh the risks and benefits on a case-by-case basis. When the transmission risk is negligible or when patients seek care more than 72 hours after a substantial exposure, nPEP is not recommended; however, clinicians might consider prescribing nPEP for patients who seek care more than 72 hours after a substantial exposure if, in their judgment, the diminished potential benefit of nPEP outweighs the potential risk for adverse events from antiretroviral medications.
Because these procedures are less common than other transmission-related activities, there have been very few case reports of HIV acquisition by this route. HIV has been transmitted via transplanted kidneys, liver, heart, pancreas, bone, and, possibly, skin grafts and through artificial insemination. HIV testing is used in these circumstances to rule out infection. Most cases of transmission through transplants of organs, bone, or tissue occurred before HIV screening was available. However, in November 2007, four organ transplant recipients contracted HIV and hepatitis C from a single organ donor . This was the first case of HIV infection resulting from transplantation since 1985. The donor was tested via ELISA for HIV and hepatitis, but the test resulted in a false negative. As with blood transfusions, donors testing antibody seronegative may pass HIV infection on to recipients . The use of nucleic acid testing and reconsideration of the use of high-risk donors have both been recommended to ensure the safety of donor recipients .
In 2009, a living donor transmitted HIV to a kidney transplant recipient . The donor had been screened 79 days prior to the transplant, but had not been retested. The CDC now recommends screening live donors no more than 7 days before organ recovery.
Primary physicians in consultation with specialists are playing an increasing role in the care of HIV-infected individuals. It is not possible for all care to be delivered by infectious disease and oncology specialists. Moreover, with early ART and prophylaxis for opportunistic infections, HIV disease shares features of other multisystem, chronic diseases characterized by acute exacerbations and end-stage manifestations.
Primary care physicians should provide risk factor assessment of their patients and, when appropriate, screening for HIV infection with pretest and post-test counseling. HIV screening may be completed after notifying the patient that the test will be performed and allowing the patient to opt out of or defer testing. Assent is inferred unless the patient declines testing . Opt-out screening does not require the pre-test counseling and explicit written consent associated with opt-in programs. Patients have reported less anxiety with opt-out screening as compared to opt-in .
Pretest counseling, which should be conducted when feasible, should include review of risk factors for HIV infection, discussion of safer sex, and the meaning of a positive test. It is recommended that, while basic information regarding HIV should be provided, extensive counseling may be eliminated if it is perceived to be a barrier to testing . Pretest counseling requirements vary by state. Post-test counseling should include information on steps to lower HIV risk. Post-test counseling for the patient who has a positive test result should include [40,41]:
Addressing emotional response and concerns associated with being HIV positive
A referral for HIV and mental health care
Emphasis on the importance of notifying the patient's sex or drug use partner(s)
Information about how to avoid transmitting HIV to others
In newly diagnosed or identified patients, the use of partner services is recommended. Partner services are a broad array of services that should be offered to persons with HIV infection and their partners . A critical function of partner services is partner notification, a process through which infected persons are interviewed to elicit information about their partners, who can then be confidentially notified of their possible exposure or potential risk. Other functions of partner services include prevention counseling, testing for HIV and other types of STIs, hepatitis screening and vaccination, treatment or linkage to medical care, linkage or referral to other prevention services, and linkage or referral to other services. The rationale for use of partner services is that appropriate use of public health resources to identify infected persons, notify their partners of their possible exposure, and provide infected persons and their partners a range of medical, prevention, and psychosocial services can have positive results .
Patients with HIV infection should be seen at regular intervals by a primary care provider to perform periodic physical examinations, monitor prognostic markers (e.g., CD4 count, viral load), initiate and monitor antiviral and prophylactic therapy, provide supportive counseling, and offer assistance with terminal care. Specialists should be consulted for patients intolerant of standard drugs, those in need of systemic chemotherapy, and those with complicated opportunistic infections. In some cases, a single specialist consultation with follow-up to the primary care physician will provide the needed expertise while ensuring continuity of care.
Standard laboratory tests for patients with HIV infection may include :
HIV serology: Standard HIV serologic testing by the ELISA method and confirmation by the Western Blot test carries a sensitivity and specificity exceeding 99%. Suspect patients with negative or indeterminate results should have repeat serologic testing in 2 to 3 months.
Quantitative HIV RNA: The measurement of HIV RNA in plasma is extremely important for determining prognosis and monitoring response to treatment. Combination antiretroviral regimens will usually produce a 50% decrease in total viral load within just a few days. HIV RNA assays should be performed approximately one month after initiation of new treatment and at 4-month intervals thereafter.
CD4 count: The CD4 count is essential for evaluating the status of the immune system. In healthy adults, levels average approximately 600–1400/mm3. It is recommended that CD4 counts be performed at 4-month intervals for most patients.
Complete blood count (CBC): Anemia, leukopenia, and thrombocytopenia are common in HIV patients in relation to progressive primary viral infection, super-infection with disseminated opportunistic pathogens, and as a complication of ART. The CBC should be repeated at 3- to 4-month intervals or more frequently if the patient's clinical course is unstable or there is prior evidence of bone marrow suppression.
Chest x-ray: Standard chest x-ray should be performed on the initial evaluation of persons found to be HIV-positive with pulmonary symptoms or a positive tuberculosis test. This provides a baseline reference for a patient population at high risk for opportunistic pulmonary complications.
Hepatitis serology and liver chemistry panel: These are indicated in the early evaluation of most patients because of the high incidence of concurrent hepatitis. Appropriate tests include detection of serologic markers for hepatitis B and C.
Syphilis serology: Standard serologic testing for syphilis is recommended annually in patients who are sexually active.
PPD skin test: The PPD tuberculin skin test should be performed annually for patients in high-risk categories including those with HIV infection. Induration greater than or equal to 5 mm is defined as a positive result in patients with HIV infection.
Fasting blood glucose and serum lipids: These tests are helpful if the patient is considered at risk for cardiovascular disease as ART can affect metabolic processes.
Genotypic resistance testing: For all patients who have pretreatment HIV RNA >1,000 copies/mL, genotypic resistance testing should be conducted.
Strategies for the treatment of HIV infection are based on an understanding of the molecular biology of HIV and the life cycle of the virus within the host cell. Antiviral agents have been developed that act predominately on processes specific to the virus particle in order to preserve the integrity of the host cell. Several potential strategies specifically aimed at interruption of the viral life cycle have been defined, including:
Preventing the virus from attaching to the CD4 receptor of the T4 lymphocyte
Interfering with uncoating of the virus within the cell, the first essential step in proviral integration into cellular DNA
Inhibiting reverse transcriptase (RT), a viral enzyme specific to retroviruses, which enables the virus to make a DNA copy from single-stranded viral RNA prior to integration into cellular DNA
Blocking viral regulatory and transactivating proteins, which are involved in the transcription and translation of viral RNA proteins from proviral DNA as the virus goes from the quiet, integrated state to active replication
Inhibiting protease, a viral enzyme responsible for the cleaving of viral proteins both before proviral integration and as the viral particles recombine into functional proteins needed for viral maturation
Preventing viral assembly and budding out of the cell
Blocking the viruses' ability to enter CD4 cells
ART combines 6 classes of agents: NRTIs, non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors, integrase inhibitors, and chemokine (C-C motif) receptor 5 (CCR5) antagonists. Initiated in 1995 in the United States, ART regimens have been effective in dramatically decreasing HIV-related morbidity and mortality and should be considered for all HIV-infected persons who qualify for such therapy. In addition to combination therapy, the sequencing of drugs and the preservation of future treatment options are also important. Three types of combination regimens may be employed as initial therapy. These include: NNRTI-based regimens, PI-based regimens, and rarely, triple-NRTI regimens. The goal of these regimens is to "save" one or more classes of drugs for later use . The U.S. Department of Health and Human Services, in their revised guidelines for the use of antiretroviral agents in HIV-infected adults and individuals, have made the distinction between NNRTI-based regimens and PI-based regimens. Treatment is also classified as "recommended" or "alternative." These changes may simplify therapeutic decisions for clinicians [42,43].
Prior to 1996, only one class of antiviral drugs, the NRTIs, was available for treatment of HIV infection. Nucleoside inhibitors act against only one step in the virus life cycle, inhibiting RT. The introduction of NNRTIs and PIs, which act at a different site or by a different mechanism, has revolutionized strategies for the treatment of this infection. For the first time, combination drug regimens employing two or more classes of antiretrovirals achieved the goal of no detectable virus, resulting in prolonged survival in many previously untreated patients. As noted above, there are 6 major classes of antiretroviral drugs.
NRTIs, used singularly or in combination, can increase CD4 count, decrease viral load, and prolong survival. Sequential monotherapy is followed eventually by clinical failure based on the emergence of drug resistance in HIV; therefore, these agents are rarely used alone in initial therapies . Combinations of two NRTIs result in better viral suppression, more sustained CD4 counts and decreased emergence of resistance. Available NRTI agents include: abacavir (Ziagen, ABC); zidovudine (Retrovir, ZDV, AZT); didanosine (Videx, ddl); stavudine (Zerit, d4T); lamivudine (Epivir, 3TC); and emtricitabine (Emtriva, Coviracil, FTC). Tenofovir (Viread, TDF) is often categorized as an NRTI but is actually a nucleotide reverse transcriptase inhibitor.
NNRTIs have a high affinity for the active site of HIV-RT. When used as a single agent, this class is associated with emergence of resistance in as little as 6 weeks. Thus, these drugs should not be used as single agents but are best employed in combination regimens for patients who have not received prior ART. Available agents include: efavirenz (Sustiva, EFV); delavirdine (Rescriptor, DLV); nevirapine (Viramune, NVP); rilpivirine (Edurant); and etravirine (Intelence).
Development of a mature infectious virus depends upon enzymatic cleavage of HIV transcribed polyprotein by HIV protease. In binding to the active site of the HIV protease, PIs interrupt the formation of mature infectious particles and reduce viral replication by as much as 99%. Resistance to PIs develops rapidly when these agents are used alone. However, in combination with nucleoside analogs the effect can last for years, often resulting in a reduction of viral load to undetectable levels. Available agents include: indinavir (Crixivan, IDV); nelfinavir (Viracept, NFV); ritonavir (Norvir, RTV); saquinavir (Invirase, Fortovase, SQV); lopinavir/ritonavir (Kaletra); atazanavir (Reyataz, ATZ); tipranavir (Aptivus, TPV); darunavir (Prezista; DRV); and fosamprenavir (Lexiva, FPV).
It was discovered that both fatal and non-fatal intracranial hemorrhage occurred in 13 out of 6,840 individuals using tipranavir in clinical trials. It was also found that tipranavir can inhibit platelet aggregation . The FDA Center for Drug Evaluation and Research has approved safety labeling changes for tipranavir that include warnings of the increased possibility of intracranial hemorrhage and platelet aggregation inhibition as well as an increased risk for clinical hepatitis when the drug is taken in combination with ritonavir . Darunavir and tipranavir are both approved to be used for patients who have not responded to treatment with other ART; when used, these drugs are co-administered with a low dose of ritonavir .
In 2003, the FDA approved the drug enfuvirtide (Fuzeon), the first new class of anti-HIV drug in seven years. Enfuvirtide, a fusion inhibitor, works by blocking the ability of HIV to infect healthy CD4 cells. When used in combination with other anti-HIV medications, enfuvirtide can reduce the amount of HIV in the blood and increase the number of CD4 cells, slowing the progression of HIV in patients who have developed resistance to currently available medications. Enfuvirtide is administered as a twice-daily subcutaneous injection .
In August 2007, maraviroc (Selzentry, UK-427) was approved by the FDA for patients with CCR5-tropic HIV-1 infection. Maraviroc is a CCR5 antagonist; it blocks replication of the virus by preventing it from entering noninfected CD4 cells via the predominant route of entry, the CCR5 co-receptor . This medication is intended for use in combination with other antiretroviral agents in treatment-experienced patients with evidence of viral replication and HIV-1 strains resistant to multiple ART . Because both fusion inhibitors and CCR5 antagonists block HIV from entering CD4 cells, they are sometimes grouped together under the category of entry inhibitors.
In 2007, the FDA approved raltegravir, the first agent in a class known as integrase strand transfer inhibitors, or INSTIs. The FDA approved a second integrase inhibitor, dolutegravir, in 2013 . These agents act by preventing the viral DNA from inserting into the host DNA, effectively limiting infection of additional cells and decreasing viral load . Raltegravir and dolutegravir are approved for use in combination with other antiretrovirals in treatment-experienced and treatment-naïve patients with evidence of HIV replication. The integrase inhibitor elvitegravir is only approved to be included in the combination formulation Stribild; it is not available as a stand-alone therapy.
The decision to initiate ART is one that requires careful discussion with the patient, usually in consultation with an infectious disease specialist or other physician well-versed in the use of ART. Physicians and patients alike should be aware of the advantages, potential toxicities, and complexity of monitoring therapy. At the present time, the most active triple-drug regimen (for example, two nucleoside analogs and a PI) in a previously untreated patient can be expected to reduce the viral load below detectable levels, increase CD4 counts by an average of 100–150/mm3, reduce the risk of HIV-associated complications, and prolong survival. However, the ability to achieve this advantage depends on the patient's willingness to accept a complex medical regimen that requires "many pills," rigorous compliance, frequent follow-up, and moderate risk for drug toxicity.
One strategy to improve patient compliance has been to combine more than one drug into a single pill, making it easier for patients to adhere to their medication regimen. Examples of such drug combinations include Combivir, Epzicom, Trizivir, Truvada, Complera, Atripla, or Stribild therapy. Trizivir is a fixed-dose combination of Ziagen (abacavir/ABC), Retrovir (zidovudine/AZT), and Epivir (lamivudine/3TC). Trizivir is not recommended for treatment in adults or adolescents who weigh less than 40 kilograms because it is a fixed-dose tablet. Combivir is a combination of zidovudine/AZT and lamivudine/3TC [50,51]. Truvada is a combination of emtricitabine and tenofovir DF, but it is not recommended for use as part of a triple nucleoside regimen. Truvada has also been approved for pre-exposure prophylaxis, as will be discussed in detail later in this course. Epzicom contains both abacavir and lamivudine. Atripla is a combination of one NNRTI and two NRTIs: efavirenz, tenofovir, and emtricitabine. Complera consists of tenofovir, emtricitabine, and rilpivirine. Stribild, the first combination containing four drugs, includes elvitegravir, cobicistat, emtricitabine, and tenofovir.
The approval and availability of the medications listed in this course are subject to change. In addition to those medications that have been FDA-approved for the treatment of HIV, there is a long list of investigational, or "pipeline," drugs being tested in clinical trials. For more information on those agents and the trials, please visit the U.S. Department of Health and Human Services AIDS info website at http://aidsinfo.nih.gov.
Antiretroviral therapy should be initiated for all patients infected with HIV in order to reduce the risk of disease progression and limit the transmission . The greatest level of evidence for initiation of therapy is for patients with lower CD4 T-cell counts (<350 cells/mm3), but there is growing evidence that any untreated HIV infection is associated with development of non-AIDS-defining diseases . Advances in the development of antiretroviral medications and combination tablets makes adherence to therapy more effective, more convenient, and better tolerated than regimens used in the past. Deferral of therapy may be considered if adherence will be very difficult or impossible, comorbidities complicate or prohibit antiviral therapy, or a patient is considered a long-term non-progressor .
For treatment-naïve patients, initial recommended therapy generally consists of a regimen of emtricitabine and tenofovir plus either a PI, an NNRTI, or an INSTI. These regimens result in maximum reduction of viral load for the longest period of time. When used as initial therapy, these regimens will achieve the goal of no detectable virus in approximately 60% to 80% of patients.
The NNRTI-based regimen adds efavirenz, while the INSTI-based therapy includes dolutegravir or raltegravir. The recommended PI-based regimen consists of tenofovir, emtricitabine, ritonavir, and either atazanavir or darunavir . Nine additional combinations have been identified as possible alternative therapies or are recommended for specific patient populations.
Treatment-experienced patients should be regularly monitored to assess compliance with and effectiveness of the prescribed regimen. For patients who begin to display immunologic failure (inadequate CD4 response despite virologic suppression), switching to a new regimen may be considered . Drug resistance testing should be undertaken to determine if an agent is no longer effective. Untreated coinfections and other medical conditions may contribute to treatment failure.
Depending on the CD4 count and other risk factors, asymptomatic patients may benefit from treatment to prevent opportunistic infections. In many cases, ART is useful in the prevention and treatment of these infections. Recommendations for antimicrobial prophylaxis of opportunistic infections are summarized in Table 3 according to guidelines provided by the CDC, National Institutes of Health, and IDSA . Prophylactic therapy for these conditions is strongly recommended because these infections are relatively common in HIV patients, preventive therapy is simple and cost effective, and efficacy has been established in clinical studies. In addition, all patients should be vaccinated with pneumococcal vaccine. Hepatitis B vaccination should be considered in patients whose serologic testing indicates susceptibility.
PROPHYLAXIS TO PREVENT FIRST EPISODE OF OPPORTUNISTIC DISEASE AMONG ADULTS AND ADOLESCENTS INFECTED WITH HIV
|Pneumocystis carinii pneumonia (PCP)||CD4 count <200 cells/mm3 (AI), or oropharyngeal candidiasis (AII), or CD4 <14% (BII), or a history of AIDS-defining illness (BII), or CD4 count >200 but <250 cells/mm3 if monitoring CD4 cell count every 3 months is not possible (BII)||Trimethoprim-sulfamethoxazole (TMP-SMZ) 1 double-strength (DS) daily (AI), or TMP-SMX 1 single-strength (SS) daily (AI)||TMP-SMX 1 DS three times weekly (TIW) (BI); or dapsone 100 mg daily or 50 mg twice daily (BI); or dapsone 50 mg daily + pyrimethamine 50 mg + leucovorin 25 mg weekly (BI); or dapsone 200 mg + pyrimethamine 75 mg + leucovorin 25 mg weekly (BI); or aerosolized pentamidine 300 mg via Respirgard II nebulizer every month (BI); or atovaquone 1500 mg daily (BI); or atovaquone 1500 mg + pyrimethamine 25 mg + leucovorin 10 mg daily (CIII)|
|Toxoplasma gondii encephalitis||Toxoplasma immunoglobulin G (IgG)-positive patients with CD4 count <100 cells/mm3 (AII). Seronegative patients receiving PCP prophylaxis not active against toxoplasmosis should have toxoplasma serology retested if CD4 count decline to <100 cells/mm3 (CIII). Prophylaxis should be initiated if seroconversion occurred (AII).||TMP-SMX 1 DS daily (AII)||TMP-SMX 1 DS TIW (BIII); or TMP-SMX 1 SS daily (BIII); or dapsone 50 mg daily + pyrimethamine 50 mg + leucovorin 25 mg weekly (BI); or dapsone 200 mg + pyrimethamine 75 mg + leucovorin 25 mg weekly (BI); or atovaquone 1500 mg daily (CIII); or atovaquone 1500 mg + pyrimethamine 25 mg + leucovorin 10 mg daily (CIII)|
|Latent Mycobacterium tuberculosis infection (LTBI)||A positive screening test for LTBI, with no evidence of active TB and no prior treatment for active TB or LTBI (AI); or close contact with a person with infectious TB, regardless of screening test results (AII)||Isoniazid (INH) 300 mg + pyridoxine 25 mg daily for 9 months (AII); or INH 900 mg biweekly (by direct-observation therapy) + pyridoxine 25 mg daily for 9 months (BII).||Rifampin 600 mg daily for 4 months (BIII); or rifabutin (dose adjusted based on concomitant ART) for 4 months (BIII). For drug-resistant TB, consult an expert or public health authorities.|
|Disseminated Mycobacterium avium complex (MAC) disease||CD4 count <50 cells/mm3 after ruling out active disseminated MAC disease based on clinical assessment (AI)||Azithromycin 1200 mg once weekly (AI); or clarithromycin 500 mg twice daily (AI); or azithromycin 600 mg twice weekly (BIII)||Rifabutin 300 mg daily (dose adjusted based on concomitant ART) (BI); rule out active TB before starting|
|Streptococcus pneumoniae infection||Individuals who have not received any pneumococcal vaccine, regardless of CD4 count||13-valent pneumococcal conjugate vaccine (PCV13) 0.5 mL IM x 1 (AI), followed in 8 weeks by PPV23 if CD4 count ≥ 200 cells/mm3||23-valent pneumococcal polysaccharides vaccine (PPV23) 0.5 mL IM x 1 (BII)|
|Influenza A and B virus infection||All HIV-infected patients (AIII)||
Inactivated influenza vaccine annually (AIII)
|Note: Live-attenuated influenza vaccine is contraindicated in HIV-infected patients (AIII).|
|Syphilis||Individuals exposed to a sex partner with a diagnosis of primary, secondary, or early latent syphilis within past 90 days (AII); or individuals exposed to a sex partner >90 days before syphilis diagnosis in the partner, if serologic test results are not available immediately and the opportunity for follow-up is uncertain (AIII)||Benzathine penicillin G 2.4 million units IM for 1 dose (AII)||For penicillin-allergic patients, doxycycline 100 mg twice daily for 14 days (BII); or ceftriaxone 1 g IM or IV daily for 10–14 days (BII), or azithromycin 2 g for 1 dose (BII) (not recommended for MSM or pregnant women [AII])|
|Histoplasma capsulatum infection||CD4 count <150 cells/mm3 and at high risk because of occupational exposure or living in a community with a hyperendemic rate of histoplasmosis (>10 cases/100 patient-years) (BI)||Itraconazole 200 mg daily (BI)||—|
|Coccidioidomycosis||A new positive IgM or IgG serologic test in patients who live in a disease-endemic area and with CD4 count <250 cells/mm3 (BIII)||Fluconazole 400 mg daily (BIII)||—|
|Varicella-zoster virus (VZV) infection (pre-exposure)||Patients with CD4 counts≥200 cells/µL who have not been vaccinated, have no history of varicella or herpes zoster, or who are seronegative for VZV (CIII)||
Primary varicella vaccination (Varivax™), 2 doses (0.5 mL SQ each) administered 3 months apart (CIII).
If vaccination results in disease because of vaccine virus, treatment with acyclovir is recommended (AIII).
|VZV-susceptible household contacts of susceptible HIV-infected persons should be vaccinated to prevent potential transmission of VZV to their HIV-infected contacts (BIII).|
|Varicella-zoster virus (VZV) infection (post-exposure)||Close contact with a person with chickenpox or herpes zoster and is susceptible (i.e., no history of vaccination or of either condition or known to be VZV seronegative) (AIII)||Varicella-zoster immune globulin (VariZIG™) 125 IU IM per 10 kg (maximum 625 IU), administered as soon as possible and within 10 days after exposure (AIII)||Acyclovir 800 mg 5 times per day for 5–7 days (BIII); or valacyclovir 1 g three times per day for 5–7 days (BIII)|
|Human papillomavirus (HPV) infection||Age 13 to 26 years (BIII)||HPV quadrivalent vaccine 0.5 mL IM at months 0,1–2, and 6 for men and women (BIII); or HPV bivalent vaccine 0.5 mL IM at months 0,1–2, and 6 for women (BIII)||—|
|Hepatitis B virus (HBV) infection||Patients without chronic HBV or without immunity to HBV (i.e., anti-HBs <10 IU/mL) (AII); or patients with isolated anti-HBc and negative HBV DNA (BII). Early vaccination is recommended before CD4 count falls below 350 cells/µL (AII). However, in patients with low CD4 cell counts, vaccination should not be deferred until CD4 count reaches >350 cells/mm3, because some patients with CD4 counts <200 cells/mm3 do respond to vaccination (AII).||HBV vaccine IM (Engerix-B 20 µg/mL or Recombivax HB 10 µg/mL) at 0, 1, and 6 months (AII); or combined hepatitis A and B vaccine (Twinrix) 1 mL IM as a 3-dose (0, 1, and 6 months) or 4-dose series (days 0, 7, 21 to 30, and 12 months) (AII)||—|
|Malaria||Travel to disease-endemic area||Recommendations are the same for HIV-infected and HIV-uninfected patients.||—|
|Penicilliosis||Patients with CD4 cell counts <100 cells/mm3 who live or stay for a long period in rural areas in northern Thailand, Vietnam, or Southern China (BI)||Itraconazole 200 mg once daily (BI||Fluconazole 400 mg once weekly (BII)|
|*All medications are taken orally unless otherwise indicated.|
RECOMMENDATIONS RATING SCHEME
|Strength of Recommendation|
|Level of Evidence|
|I||One or more randomized trials with clinical outcomes and/or validated laboratory endpoints|
|II||One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes|
The CDC has developed guidelines for the prevention of opportunistic infections among HIV-infected individuals. The report offers guidelines specific to each type of opportunistic infection. The report can be viewed at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf.
The HIV/AIDS Bureau of the U.S. Department of Health and Human Services has established guidelines for the primary care of patients living with HIV/AIDS. These guidelines stress the importance of establishing mechanisms for coordination and communication to ensure good care for people with HIV/AIDS . A multidisciplinary approach, utilizing the special skills of nurses, pharmacists, nutritionists, social workers, and case managers, is highly desirable to best address patients' needs regarding housing, medical insurance, emotional support, financial benefits, substance abuse counseling, and legal issues.
There are several special issues that often arise in the HIV/AIDS patient population. Because HIV occurs with greater frequency in gay and ethnic minority (particularly black) communities, cultural competency and sensitivity are core elements of care. The guidelines recommend that providers demonstrate respect and provide excellent care to patients with various cultural backgrounds, beliefs, and sexual orientations . Other socioeconomic issues, including poverty, professional and personal stigma, lack of insurance, and illegal immigration status, occur more frequently among these groups and can impact the ability to provide care.
Patient education is a vital aspect of care that begins during the initial evaluation and continues throughout the course of care . Using basic language and verifying patients' understanding of medical terms and concepts can strengthen information provided and ensure that issues are fully addressed. Patient education in the primary care setting should include :
A definition of HIV
Natural history of HIV disease and consequences of immune system destruction
Interpretation of laboratory results
Indications and goals of treatment, including potential benefits and risks
Early signs and symptoms and prophylaxis of opportunistic diseases
Treatment options and compliance
Insurance information and access to medication
Support services and support groups
For comprehensive human services to assist those with HIV infection, please contact the Washington State Department of Health HIV Care Early Intervention Program (EIP) or the Medical Case Management Program at 360-236-3426, or visit their website at http://www.doh.wa.gov/YouandYourFamily/IllnessandDisease/HIVAIDS/HIVCareClientServices.
The route of transmission, clinical manifestations, survival time, and the impact on reproductive health, such as childbearing and gynecologic disease, are all examples of how HIV affects women differently than men. In addition to the clinical manifestations of HIV disease in women, social factors have a significant impact on the health of women with HIV.
The 2014 case definition for HIV infection includes tests and multi-test algorithms that were not available when the AIDS case definition was previously revised. The revised case definition for HIV infection also permits states to report cases to the CDC based on the result of any test licensed for diagnosing HIV infection in the United States .
Women make up 24% of those living with HIV in the United States . The rate of new HIV infections in women declined 21% between 2008 and 2010, and women accounted for 20% of new cases in 2010. Women of color have been disproportionately affected by HIV/AIDS. In the United States, the odds of a woman being diagnosed with HIV in her lifetime are significantly higher for black women (1 in 32) and Latinas (1 in 106) than for white women (1 in 526) . AIDS is the fourth leading cause of death among black women 25 to 44 years of age in the United States, but it does not rank among the top ten leading causes of death among white women in the same age group. Among all women, those 25 to 34 years of age accounted for the highest number of new infections in 2010 (29%), followed by women 35 to 44 years of age (25%) and 13 to 24 years of age (22%) . Women are more likely to be infected through heterosexual intercourse (84% in 2010) than any other type of transmission.
Although AIDS cases have been identified throughout the United States, most are concentrated in large urban areas; for example, approximately two-thirds of cases in Washington are in King County [28,94]. The most rapidly increasing incidence of AIDS is among women who have had heterosexual contact with an HIV-infected man. Cases of woman-to-woman sexual transmission have been reported and are accounted for in the CDC reporting category "other." Other possible modes of transmission that may occur among women include infection through artificial insemination (especially before the availability of HIV testing), sexual abuse or assault, contaminated instruments used for body piercing or tattooing, and healthcare-related occupational exposure. Certain female reproductive tract conditions (e.g., bacterial vaginosis, pelvic inflammatory disease, chlamydia) make HIV more serious.
The risk for acquisition of HIV and the factors that may affect seroconversion in heterosexual women are areas of research. In Europe and the United States, heterosexual monogamous couples with one HIV-infected partner and no other risk factors were followed over time. It was found that female partners of HIV-infected men were 17.5 times more likely to become infected than male partners of infected women. It was also found that the risk for infection increased in couples who did not consistently use latex condoms, were symptomatic, or had low CD4 counts. In other words, women are much more likely to become infected with HIV through heterosexual sex than men, and latex condoms, when used consistently, are an effective means of preventing transmission .
Because HIV is spread predominantly through sexual transmission, the development of chemical and physical barriers that can be used intravaginally or intrarectally to inactivate HIV and other STI pathogens is critically important for controlling HIV infection.
Researchers are developing and testing new chemical compounds that women could apply before intercourse to protect themselves against HIV and other sexually transmitted organisms. These include creams or gels, known as topical microbicides, which ideally would be non-irritating and inexpensive. In addition, microbicides should be available in both spermicidal and non-spermicidal formulations so women do not have to put themselves at risk for acquiring HIV and other STIs in order to conceive a child. The research effort for developing topical microbicides includes basic research, preclinical product development, and clinical evaluation.
The first microbicides developed to lessen the risk of HIV infection were non-specific entry inhibitors and surfactants [57,62]. These products formed physical barriers in the vagina (surfactants) or changed the vaginal chemistry (pH-modifiers, polyanions), essentially making an environment that is less conducive to the transmission of HIV. First-generation microbicides are gel products that must be applied within a few hours prior to sexual intercourse. Given the complexity of HIV transmission, it is possible that these early microbicides would only be at best 30% to 50% effective .
Today, topical microbicide research is focused primarily on new technologies for preventing HIV infection, predominantly the use of antiretroviral agents in the products' formulations. The newer microbicides include NRTIs, NNRTIs, or entry inhibitors to suppress the virus before it begins replication [57,62]. In contrast to the less specific first-generation microbicides, these products are formulated to specifically target HIV.
Because next-generation products may be formulated in sustained-release formulations (e.g., the dapivirine ring), application is not dependent upon planned sexual contact . However, resistance to the antiretroviral agents is a serious concern.
Research is being conducted to determine whether the clinical manifestations of HIV, other than those related to the reproductive tract, are different for women than for men. It appears that many symptoms and signs of acute HIV infection and non-specific manifestations, such as fevers, weight loss, and fatigue, are the same. Because past research has either excluded women altogether or included only small cohorts of women, it has been difficult to determine gender differences in the clinical course of HIV disease.
In a large, multicenter cohort study comparing mortality and disease progression between women and men, women were more likely than men to develop bacterial pneumonia, especially if they were injection drug users. In addition, women were more likely to have mycobacterial infections, whereas men had higher rates of oral hairy leukoplakia and Kaposi's sarcoma [55,56].
It is noteworthy that many healthcare providers fail to recognize recurrent vaginal candidiasis as a potential indicator of HIV . This failure to diagnose results in delays in treatment. As many as 60% of HIV-infected women also test positive for some type of human papillomavirus (HPV). HIV infection is a risk factor for higher prevalence of HPV in the cervix and increased likelihood of infection by multiple HPV types. HIV infection is associated with a high rate of cervical cancer and cervical intra-epithelial neoplasia (CIN) or squamous intra-epithelial lesions (SIL). Menstrual irregularities are also frequently reported by women with HIV .
Studies have shown that women with AIDS have a poorer prognosis than men, although this is mainly attributed to socioeconomic factors. In a large sample of women and men with HIV, it was found that women had poorer survival rates, although the rates of progression of disease were the same over a 15-month observational period. According to the National Institutes of Health, HIV-positive women whose diagnosis is timely and who receive appropriate treatment have the same survival rate as HIV-infected men . Researchers have speculated that poorer access to or use of healthcare resources (later diagnosis), domestic violence, homelessness, and lack of community support may contribute to the seemingly higher mortality rate for HIV-infected women .
HIV counseling and the offer of HIV testing to pregnant women have been universally recommended in the United States and are now mandatory in some states. Care of the HIV-infected pregnant woman should involve a collaboration between the HIV specialist caring for the woman when she is not pregnant, her obstetrician, and the woman herself. Treatment recommendations for HIV-infected pregnant women are based on the belief that therapies of known benefit to women should not be withheld during pregnancy unless there are known adverse effects on the mother, fetus, or infant that outweigh the potential benefit to the woman [30,31]. Regardless of the stage of pregnancy or childbirth, if a woman is found to be HIV-positive, there are treatment options that should be explored.
Initiation of the following therapy regimens is recommended for pregnant women with HIV in the different stages of pregnancy . Regardless of the stage of pregnancy or childbirth, if a woman is found to be HIV-positive, there are treatment options that should be explored.
The initial assessment of the HIV-positive pregnant woman should include screening for hepatitis C virus and tuberculosis infection, as well as history of side effects or toxicities from prior antiretroviral drug regimens . It is recommended that pregnant women with HIV who have not received prior therapy should begin ART. The decision to continue therapy for pregnant women who have already been receiving ART should be made collaboratively. Counseling regarding risks and benefits of ART for the patient and fetus is recommended, particularly during the first trimester of pregnancy. In general, continuation of therapy is recommended even if efavirenz is a component of the regimen, as the adverse effects of the drug are restricted to the first 5 to 6 weeks of pregnancy and pregnancy is generally not recognized until 4 to 6 weeks post-conception . If therapy is discontinued for the first trimester, all medications should be discontinued and reintroduced at the same time to prevent resistance.
As noted, women who are receiving ART who become pregnant should continue their established regimens; replacing potentially teratogenic drugs (i.e., efavirenz, combination stavudine/didanosine) in the first trimester can lead to a loss of viral control and an increased risk of perinatal transmission . Drug-resistance studies should be performed before starting or modifying ARV drug regimens in women whose HIV RNA levels are above the threshold for resistance testing (i.e., >500–1,000 copies/mL). Pregnant patients who have never received ART and with indications for treatment should be started on a regimen as soon as possible after antiretroviral drug resistance testing is completed. If HIV is diagnosed later in pregnancy, ART should be initiated immediately, without waiting for resistance testing results . The recommended ART options are the same as those established for adults with HIV; if possible, zidovudine should be used as part of the initial treatment or another NRTI agent with high placental transfer should be included as a component of the dual-NRTI backbone. Pregnant women with no indications for ART for their own health should also begin treatment as prophylaxis for perinatal transmission, but initiation of therapy may be delayed until after the first trimester .
Several effective administrations are available for women with HIV while in labor. Women who have been receiving ART should continue on the same regimen during the intrapartum period. For HIV-infected women receiving combination antiretroviral regimens who have HIV RNA <400 copies/mL near delivery, zidovudine IV is no longer recommended . Women who have not received ART prior to labor or who have RNA ≥400 copies/mL (or unknown HIV RNA) near delivery should be initiated on a continuous infusion of zidovudine IV during labor, regardless of antepartum regimen or delivery mode. When IV zidovudine is not possible, oral administration should be considered.
Some practitioners also administer a single dose of nevirapine at the onset of labor. Consideration should also be considered for adding lamivudine during labor. One trial showed similar efficacy and safety profiles for these agents, but it is unclear if there is any added benefit of intrapartum administration with either .
Infants born to patients who took ART throughout their pregnancies should be administered zidovudine for 6 weeks beginning within 6 to 12 hours of birth. Infants whose mothers had not received ART during pregnancy should be started on zidovudine (4 mg/kg orally, twice daily) for 6 weeks as soon as possible after birth and should be given 3 doses of nevirapine in the first week of life (at birth, 48 hours later, and 96 hours after the second dose) . In addition, these treatment-naïve women should be evaluated for continued ART. In some cases, if antiretroviral medications were administered during labor, zidovudine/lamivudine for 7 days after delivery may be prescribed to mothers to help prevent the development of resistance. Breastfeeding by HIV-infected mothers is not recommended; this includes women on ART . Counseling should be advised for women in the weeks following delivery, as adherence to ART is known to be poor in the postpartum period.
Patients should be registered with the Antiretroviral Pregnancy Registry, which collects observational, nonexperimental data. The registry is sponsored by GlaxoSmithKline, in affiliation with the CDC and Kendle International Inc. Women who have been treated with ART at any time during their pregnancies are eligible for registry enrollment. The telephone number for registration is (800) 258-4263, and the website is http://www.apregistry.com.
The initial case reports of pediatric AIDS in infants published in 1983 took much of the world by surprise. Initially, these reports were the subject of much discussion and controversy because many people refused to believe that children could suffer from AIDS. Over the ensuing years, there have been many advances in the recognition, diagnosis, and treatment of pediatric AIDS as well as the unfolding of a pandemic that is a worldwide concern. In the United States, effective screening of blood and improved manufacturing techniques for coagulation factors have eliminated these products as a cause of transmission. In 2010, an estimated 217 children younger than 13 years of age were diagnosed with HIV; 162 (75%) of these children were perinatally infected . Thus, the epidemic in children is closely linked to the epidemic in women . Mother-to-child transmission (MTCT) can occur during pregnancy, labor and delivery, or breastfeeding in both symptomatic and asymptomatic women.
The tragedy of MTCT is that women may be unaware of their risk. The CDC has adapted recommendations that advocate universal counseling and testing with informed consent for every pregnant woman regardless of geography, identified risk behavior, or self-identified risk. In 2005, the U.S. Preventative Services Task Force (USPSTF) published guidelines recommending the screening of all pregnant women for HIV. The benefits supporting this statement included a potential for decreased perinatal transmission of HIV resulting from maternal and neonatal ART treatment and the increased opportunity to provide counseling regarding risks associated with breastfeeding and elective cesarean delivery .
Many women do not have an identified care provider, lack insurance coverage, seek care only for acute illness, or lack access to ongoing care. Nonetheless, by making counseling and testing a component of routine prenatal care, these recommendations will improve the care given to HIV-infected pregnant women and identify infants at risk for HIV prior to their birth. The American Academy of Pediatrics recommends HIV testing of newborn infants if testing was not offered or accepted by the mother during the prenatal period or if the mother did not receive prenatal care . Testing should be offered confidentially, with counseling and informed consent provided and available healthcare services that are readily accessible.
The major advances in diagnosis and treatment are profoundly influencing the care of women and children with HIV infection. The documented ability of ZDV to interrupt MTCT has had a tremendous impact on the field of maternal and pediatric HIV. A second major advance is in the diagnosis of HIV infection in infants, which may be completed by 1 month in nonbreastfed infants with the use of virologic assays .
In settings throughout the United States, healthcare professionals encounter women and children in their daily practice. Knowledge about and understanding of the nationwide spread of HIV and its implications are crucial. Every pregnant woman must be offered an opportunity to know her HIV status in order to receive the best prenatal care and to assure prompt assessment of her newborn. Although surveys provide a statistical picture, each woman is an individual. HIV testing should always be offered after information and counseling has been provided to the pregnant woman.
More critical than pretest counseling is post-test support. Negative results provide opportunity to reinforce risk. Positive results should always be given in person, never over the phone. If the site is unable to provide continuing services, arrangements must be made for uninterrupted prenatal care that is acceptable to the woman. The diagnosis of HIV is devastating to a pregnant woman, and intense support through an identified friend or family member may be helpful. Depending on the length of gestation, the woman will have many questions regarding the pregnancy as well as her own health.
The full spectrum of HIV disease in children has become evident as children survive longer. Early in the epidemic, only the most symptomatic and ill children were diagnosed, and so death appeared to occur in infancy and early childhood for most children. It is now recognized that to understand the natural history (disease progression), the progress of infected children must be followed from birth. Several prospective studies in the United States and Europe are following the progress of infants born to HIV-infected women; these cohorts serve as the basis for our description and understanding of the disease in children. Recent reports from these groups show that the median survival for infected children is 8 years, with children with PCP and encephalopathy having the poorest prognosis and the highest mortality in the first year of life. The period from infection to onset of AIDS-defining symptoms is often referred to as the clinical latency period. However, ongoing, complex interaction occurs between the virus and the immune system. The absence of clinical symptoms does not mean that the child is truly "well." Except for age at diagnosis and type of clinical presentation, no demographic or clinical indicators have been related to prognosis. Low CD4 counts for age are the best indicators of immunodeficiency and indicators of the risk of developing opportunistic infections. Early identification of the infected infant, specific prophylactic regimens to prevent infections, and ongoing supportive care are important in improving survival.
Antiretroviral therapy is believed to play a major role in slowing progression of the disease process. Many of the antiretroviral medications approved for use in the treatment of HIV/AIDS are produced in a pediatric formulation . The pharmacologic recommendations for infants and children are based on the same regimens that have been established for adults.
For children younger than 3 years of age, the preferred NNRTI-based regimen is ritonavir-boosted lopinavir with two NRTIs . The U.S. Department of Health and Human Services recommends that efavirenz or ritonavir-boosted lopinavir and two NRTIs be used in the treatment of children 3 to 6 years of age. The preferred PI-based regimen for children 6 years of age or older consists of atazanavir with low-dose ritonavir and two NRTIs.
Children receiving ART should be monitored for side effects, adherence, efficacy and toxicity. The U.S. Department of Health and Human Services recommends evaluating all pediatric patients within 1 to 2 weeks and again within 1 to 2 months to monitor compliance, side effects, and response to treatment. Subsequently, a visit should be scheduled every 3 to 4 months, and after sustained viral suppression and stable clinical status is established with strict adherence to the regimen, follow-up may be done every 6 to 12 months . Strategies to improve adherence should focus on selecting an appropriate regimen, educating the family/caregiver, and consistent follow-up.
Serious bacterial infections, multiple or recurrent, such as septicemia, pneumonia, meningitis, bone or joint infection, or abscess of an internal organ or body cavity (excluding otitis media, superficial skin or mucosal abscesses, and indwelling catheter-related infections)
Candidiasis (esophageal or pulmonary)
Cryptosporidiosis or isosporiasis with diarrhea persisting longer than 1 month
Herpes simplex virus infection causing bronchitis, pneumonitis, or esophagitis or causing a mucocutaneous ulcer that persists for longer than 1 month
Disseminated or extrapulmonary Mycobacterium tuberculosis
Disseminated Mycobacterium, other species or unidentified species
Pneumocystis carinii pneumonia
Progressive multifocal leukoencephalopathy
Recurrent salmonella septicemia (nontyphoid)
Toxoplasmosis of the brain
The presence of several HIV-related complications in a child results in physical and psychosocial suffering as well as the need for multiple medications and treatments, including hospitalization. The frequency and intensity of contact with the healthcare providers increase. Physical symptoms include pain (abdominal, headache, extremity, and overall body pain being the most frequently reported), nausea, vomiting, diarrhea, anorexia, loss of function and mobility, weakness, changes in cognition, seizures, shortness of breath and cough, itching, and skin lesions. Psychosocial problems include depression, anger, sorrow, fear, isolation, and ambivalence. Medications and treatments for the disease, although life sustaining, often cause uncomfortable side effects, interfere with quality of life, and produce multiple added stressors for families.
Rapidly progressing disease in the early years of life causes a particular set of complications frequently seen in young children with HIV. These symptoms include failure to thrive with inability to ever achieve appropriate weight and growth, severe progressive encephalopathy with spasticity and developmental delays, severe immune dysfunction, multiple infections, and multi-organ failure. Infants with this group of symptoms often suffer from severe allodynia (painful hypersensitivity to touch), are difficult to console, and frequently cannot be fed by mouth. Such cases pose a significant challenge to caregivers. Pediatric patients with advanced HIV disease frequently have multiple hospitalizations and require treatment with intravenous (IV) medications, either as induction therapy for CMV (retinitis) or as curative therapy for septicemia. Invasive diagnostic studies such as biopsies may be required, or surgical procedures may be needed. Children with advanced HIV disease are most frequently hospitalized for problems such as serious bacterial infections (pneumonia, sepsis, abscesses, sinusitis); new or recurring opportunistic infections (esophagitis, Mycobacterium avium complex, CMV retinitis, herpes); fever and pain of unknown cause; weight loss and nutritional interventions (nasogastric feedings or parenteral nutrition); and hematologic problems such as anemia requiring transfusion, thrombocytopenia requiring infusions of platelets, and intravenous immunoglobulin and neutropenia accompanied by fever.
Critical care is often required when a patient is admitted with a life-threatening illness believed to be treatable. The most common problems requiring critical care are respiratory failure due to PCP or other overwhelming pulmonary infection and septic shock.
Approximately 17% of newly diagnosed cases of HIV/AIDS in 2011 occurred in individuals 50 years of age or older, and 39% of all persons living with HIV/AIDS are 50 years of age or older [15,65]. However, until recently, there had been little attention given to this group . HIV/AIDS has traditionally been thought to be the disease of the young; therefore, in the past, prevention and education campaigns had not been targeted toward older adults. However, evidence points to the increasing number of infected older people and a need for change in prevention and education campaigns. Some older persons may have less knowledge about HIV and risk reduction strategies. Due to divorce or being widowed and the availability of medications to treat erectile dysfunction, increasing numbers of older people are becoming sexually active with multiple partners [65,66]. For postmenopausal women, contraception is no longer a concern, and they are less likely to use a condom. Furthermore, vaginal drying and thinning associated with aging can result in small tears or cuts during sexual activity, which also raises the risk for infection with HIV/AIDS . Studies indicate that at-risk individuals in this age group are one-sixth as likely as younger at-risk adults to use condoms during sex . The combination of these factors increases the risk for unprotected sex with new or multiple partners in this age group, thereby increasing their risk for AIDS.
This increase must be considered when evaluating older patients. Individuals in this age group are significantly less likely to be tested for HIV . Elderly people presenting with confusion or altered mental status or having severe bouts of pneumonia may first be evaluated for other possibilities before HIV is considered. Many physicians do not suspect HIV in their older patients and miss the opportunity to suggest testing, which can result in delayed diagnosis and treatment.
Early possible signs of immunosuppression that are frequently overlooked or mistakenly attributed to aging include thrush and skin problems, especially seborrheic dermatitis, herpes zoster, and recurrent herpes simplex virus type 2 in a person who does not have a history of it. When HIV is not recognized or treated, the most typical opportunistic infections are PCP and recurrent bacterial pneumonia, CMV, and Mycobacterium tuberculosis or Mycobacterium avium complex. PCP can present as bacterial pneumonia, bronchitis, or congestive heart failure. Early HIV symptoms in the elderly, such as fatigue and weight loss, may appear to be a normal part of aging, and AIDS-related dementia is often mistaken for Alzheimer's disease.
In 2012, the FDA approved the first medication for the prevention of sexually transmitted HIV infection, the combination drug Truvada (emtricitabine/tenofovir DF) . In conjunction with safer sex practices, Truvada has been found to be partially effective as pre-exposure prophylaxis in high-risk patients . The Chemoprophylaxis for HIV Prevention in Men study, also known as iPrEx, studied the effect of once daily Truvada in 2,499 HIV-seronegative men or transgender women who have sex with men compared to placebo . Researchers found that persons receiving Truvada experienced a 44% reduction in the incidence of HIV after a median of 1.2 years compared to placebo. Pre-exposure prophylaxis was most effective among participants at particularly high risk for HIV (i.e., self-reports of unprotected receptive anal intercourse).
In 2014, the CDC and the U.S. Department of Health and Human Services released clinical practice guidelines for pre-exposure prophylaxis for the prevention of HIV Infection . This new guideline outlines indications for prophylaxis as one prevention option for HIV transmission. The most important first step in determining if an individual is a candidate for pre-exposure prophylaxis is a thorough history, including sexual and injection drug activities. All candidates will be adults without an acute or established HIV diagnosis. Pre-exposure prophylaxis is indicated for high-risk MSM, meaning those who have had any male sex partners in the past 6 months, are not in a monogamous partnership with a recently tested, HIV-negative man, and have one of the following :
Anal sex without condoms (receptive or insertive) in the past 6 months
Any STI diagnosed or reported in the past 6 months
An ongoing sexual relationship with an HIV-positive man
Prophylaxis is also recommended for high-risk heterosexual adults who have had sex with an opposite sex partner(s) in the past 6 months, are not in a monogamous partnership with a recently tested, HIV-negative partner, and one of the following :
Is a man who has sex with both women and men (behaviorally bisexual)
Infrequently uses condoms during sex with one or more partners of unknown HIV status who are known to be at substantial risk of HIV infection (IDU or bisexual male partner)
Is in an ongoing sexual relationship with an HIV-positive partner
IDUs are also considered candidates for pre-exposure prophylaxis if they meet certain criteria. The guideline states that persons who have injected drugs not prescribed by a clinician in past 6 months may be candidates for prophylaxis if they also are positive for one of the following factors :
Any sharing of injection or drug preparation equipment in the past 6 months
Been in a methadone, buprenorphine, or buprenorphine/naloxone treatment program in the past 6 months
Increased risk of sexual acquisition (based on the previously outlined criteria)
Only fixed-dose combination tenofovir and emtricitabine (Truvada) taken daily is approved for pre-exposure prophylaxis, and it is considered the recommended first-line option [44,99]. However, because tenofovir alone has been proven effective in trials with IDU and heterosexually active men and women, it is the alternative option for these populations . No other antiretroviral regimens should be used for pre-exposure prophylaxis.
All patients prescribed Truvada for pre-exposure prophylaxis must have a negative HIV test prior to initiating treatment and every 3 months thereafter. In addition, patients should be advised regarding possible side effects and the continued necessity for safe sex practices. Eligible patients should also be screened for hepatitis B and have a confirmed creatinine clearance of 60 mL per minute or greater .
Achieving an end to the AIDS epidemic will require the development of an effective vaccine. Both preventive and therapeutic vaccines are being studied for use in the fight against HIV. Preventive vaccines are developed to protect individuals from contracting HIV, while the goal of therapeutic vaccines is to boost immune response to and better control existing HIV infection . Of course, the ultimate goal in vaccine research is a vaccine that will prevent infection; however, despite several trials, no vaccine effective in preventing HIV has been discovered.
There are three types of preventive vaccines being studied for the prevention of HIV: subunit vaccines, recombinant vector vaccines, and DNA vaccines . Subunit vaccines, also known as component or protein vaccines, contain only genetically engineered parts of HIV rather than the whole virus. Theoretically, these parts, or subunits, may induce an anti-HIV immune response, but the effectiveness of preventing future infection is unknown.
DNA vaccines contain a portion of a virus's genetic material. The partial HIV DNA is injected into the body, where existing cells produce HIV proteins. As a result, the body produces an immune response against HIV.
Finally, recombinant vector vaccines utilize as attenuated non-HIV virus, or vector, to carry a portion of HIV's genetic material into the recipient's body. As with the DNA vaccines, the HIV genes create proteins, which in turn stimulate an immune response. Because most HIV recombinant vector vaccines deliver several HIV genes, they may create a stronger immune response. Canarypox virus, cowpox virus, Venezuelan equine encephalitis, and adenovirus-5 are all being studied as possible vectors for future HIV vaccines .
The possibility of combining two or more types of vaccines in a booster system to strengthen immune response is being studied. This prime-boost vaccination strategy may stimulate different parts of the immune system and enhance the effectiveness of the vaccines .
It is important to note that none of these vaccines contains the viral material necessary to develop HIV infection. Those vaccines that contain genetic material from the virus do not carry the full virus or the complete set of genes necessary for infection .
The International AIDS Vaccine Initiative (IAVI) is working to speed the development and distribution of preventive AIDS vaccines, focusing on four areas: mobilizing support through advocacy and education; accelerating scientific progress; encouraging industrial participation in AIDS vaccine development; and assuring global access.
Many adolescents engage in behaviors that put them at risk for HIV infection. According to the CDC, nearly 50% of high school students have engaged in intercourse . Approximately 40% of sexually active high school students had not used a condom at last sexual intercourse; 2.3% had ever injected an illegal drug . The CDC asserts that renewed educational efforts that reach all students before risk behaviors are initiated and that seek to delay the onset of sexual activity, increase condom use among students who are sexually active, and decrease injection drug use are warranted . Education and interventions are considered vital to the reduction of high-risk behaviors in this population.
Although more than 90% of adolescents report having received education on HIV prevention in school, the content of these discussions may not provide adequate information on the subject. Furthermore, the American Academy of Pediatrics determined that school-based education and intervention programs do not provide the necessary opportunities for confidential discussions or targeted counseling . Healthcare professionals have a unique opportunity to intervene in this population to provide accurate and complete information on HIV transmission and risk reduction.
The CDC HIV/AIDS Prevention Research Synthesis Project collects and analyzes systematic reviews and identifies evidence-based interventions that have been proven effective in eliminating or reducing sex- or drug-related risk behaviors, reducing the rate of new HIV/STD infections, or increasing HIV-protective behaviors . As of 2014, 82 best-evidence interventions had been identified, many of which target specific populations. Intervention packages and more information on these interventions are available at http://www.cdc.gov/hiv/dhap/prb/prs.
The state of Washington has specific laws and statutes governing HIV testing, including sections devoted to informed reporting, consent, and confidentiality. According to the Washington Administrative Code, healthcare professionals must report diagnoses of HIV and/or AIDS local health departments within 3 business days . According to the Washington Department of Health, laboratories are required to report each test result (except in King County or when another local health department is designated by the Department of Health), including :
Tests confirming HIV infection (e.g., positive Western Blot assays, p24 antigen tests, and viral culture tests): Within 2 business days
HIV viral load results, both detectable and undetectable: Monthly
CD4+ (T4) lymphocyte results of any value (patients aged thirteen or older): Monthly
For each result, the lab must provide the test result, date of collection, requesting health care provider, and patient information including name, sex, date of birth, address, and telephone number. As of July 1, 2011, healthcare providers requesting a laboratory test for HIV/AIDS are required to provide the following information :
Patient address including zip code
Patient date of birth
Name of the principal healthcare provider
Telephone number of the principal healthcare provider
Type of test requested
Type of specimen
Date of ordering specimen collection
Many HIV and AIDS case reports are initiated from a laboratory result. However, when testing takes place outside of Washington, it is the healthcare provider's responsibility to ensure that the diagnosis is reported to the public health office. According to Washington Administrative Code, in these cases healthcare providers can meet this requirement by arranging for the referral laboratory to notify either the local health department, the department, or both; or forwarding the notification of the test result from the referral laboratory to the local health department, the department, or both .
Knowledge of statutes related to HIV/AIDS testing, reporting, and counseling may be useful in ensuring that public health is served and patients' rights are protected. To view the Washington Administrative Code Chapters 246-100 and 246-101 pertaining to communicable and notifiable diseases, please visit the Washington Legislature's website at http://apps.leg.wa.gov/wac/default.aspx?cite=246.
Although prevention and new medical interventions may reduce the pace of the epidemic, HIV will be a significant disease for many years both in the United States and the world. Education provides the opportunity to ensure that healthcare professionals have the information necessary to provide the best possible care for persons with HIV. Healthcare administrators have the responsibility to recognize the special stresses, and the generic ones, associated with caring for HIV patients and to address those with meaningful changes in case load and staff support. Those who specialize in HIV care must identify ways to renew themselves through education, individual support, staff support, and variation of workload so that they can continue to contribute their valuable expertise to patients with HIV. With no easy cure in sight, healthcare professionals have the opportunity to work with patients to help them achieve and maintain their optimal level of health throughout the continuum of HIV disease.
1. Quinn TC. Epidemiology of HIV infections: international and U.S. perspectives. Hopkins HIV Rep. 1998;10(3):11-12.
2. The Associated Press. Ancestry of HIV Virus Traced. Available at http://www.msnbc.msn.com/id/3076791/ns/health-aids/t/ancestry-hiv-virus-traced. Last accessed March 17, 2014.
3. Centers for Disease Control and Prevention. HIV-2 infection surveillance—United States, 1987–2009. MMWR. 2011;60(29): 985-988.
5. Mann JM, Chin J, Piot P, Quinn T. The international epidemiology of AIDS. Sci Am. 1988;259(4):82-89.
6. UNAIDS. Fact Sheet: Asia. Available at http://data.unaids.org/Publications/Fact-Sheets04/fs_asia_en.pdf. Last accessed March 11, 2014.
7. Klein R. Uni-Gold Recombigen HIV: FDA News Release. Available at http://www.cdc.gov/hiv/topics/testing/resources/press_releases/FDArelease.htm. Last accessed March 11, 2014.
8. Joint United Nations Programme on HIV/AIDS. 2013 Global Fact Sheet. Available at http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/20130923_FactSheet_Global_en.pdf. Last accessed March 11, 2014.
9. Bond L1, Wheeler DP, Millett GA, LaPollo AB, Carson LF, Liau A. Black men who have sex with men and the association of down-low identity with HIV risk behavior. Am J Public Health. 2009;99(Suppl 1):S92-95.
10. Centers for Disease Control and Prevention. HIV transmission through transfusion—Missouri and Colorado, 2008. MMWR. 2010;59(41):1335-1339.
11. U.S. Department of State. Next Steps for U.S. Africa Policy: A Debrief of President Bush's Trip to Africa. Available at http://www.cgdev.org/doc/event%20docs/7.18.03-Bush%20Africa%20debrief/AfricaDebriefTranscript.pdf. Last accessed March 11, 2014.
12. Office of U.S. Global AIDS Coordinator. About PEPFAR. Available at http://www.pepfar.gov/about/index.htm. Last accessed March 11, 2014.
13. Centers for Disease Control and Prevention. New Hope for Stopping HIV: Testing and Medical Care Save Lives. Available at http://www.cdc.gov/vitalsigns/HIVTesting. Last accessed March 11, 2014.
14. Centers for Disease Control and Prevention. HIV transmitted from a living organ donor—New York City, 2009. MMWR. 2011;60(10):297-301.
15. Centers for Disease Control and Prevention. HIV/AIDS Surveillance Report. Vol. 23. Available at http://www.cdc.gov/hiv/library/reports/surveillance/2011/surveillance_Report_vol_23.html. Last accessed March 11, 2014.
16. Centers for Disease Control and Prevention. Incorporating HIV prevention into the medical care of persons living with HIV. MMWR. 2003;52(RR12):1-24.
17. Centers for Disease Control and Prevention. Advancing HIV prevention: new strategies for a changing epidemic—United States, 2003. MMWR. 2003;52(15):329-332.
18. Centers for Disease Control and Prevention. CDC-Developed Breakthrough Technology Allows Clearest Picture to Date of HIV Infections in the U.S.: A Methods Discussion. Available at http://www2a.cdc.gov/podcasts/media/pdf/HIV_Breakthrough.pdf. Last accessed March 11, 2014.
19. Centers for Disease Control and Prevention. Press Release: National HIV Prevention Conference Echoes Themes of HHS New HIV Prevention Initiative. Available at http://www.cdc.gov/media/pressrel/r030728.htm. Last accessed March 11, 2014.
21. Constantine N. HIV Antibody Assays. Available at http://hivinsite.ucsf.edu/InSite?page=kb-02-02-01. Last accessed March 17, 2014.
22. U.S. Food and Drug Administration. FDA Approves First Rapid Diagnostic Test to Detect Both HIV-1 Antigen and HIV-1/2 Antibodies. Available at http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm364480.htm. Last accessed March 11, 2014.
23. Peterson LR. Duration of time from onset of human immunodeficiency virus type 1 infectiousness to development of detectable antibody. Transfusion. 1994;34(4):283-289.
24. Centers for Disease Control and Prevention. Using the BED HIV-1 Capture EIA Assay to Estimate Incidence Using STARHS in the Context of Surveillance in the United States. Available at http://www.cdc.gov/hiv/pdf/library_factsheet_HIV_usingTheBed_HIV-1_2007.pdf. Last accessed March 17, 2014.
25. Henry J. Kaiser Family Foundation. Crystal Meth Use Fuels Rise in HIV Cases Among White MSM; "Down Low" Term Should Apply To All Races, Studies Say. Available at http://www.kaiserhealthnews.org/daily-reports/2005/june/16/dr00030788.aspx?referrer=search. Last accessed March 17, 2014.
26. Centers for Disease Control and Prevention. Oral Sex and HIV Risk. Available at http://www.cdc.gov/hiv/risk/behavior/oralsex.html. Last accessed March 17, 2014.
27. U.S. Food and Drug Administration. FDA Approves New Drug to Treat HIV Infection. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm364744.htm. Last accessed March 12, 2014.
28. Henry J. Kaiser Family Foundation. HIV/AIDS Policy Fact Sheet: Women and HIV/AIDS in the United States. March 2014. Available at http://kff.org/hivaids/fact-sheet/women-and-hivaids-in-the-united-states/. Last accessed March 13, 2014.
29. Centers for Disease Control and Prevention. Zidovudine for the prevention of HIV transmission from mother to infant. MMWR. 1994;43(16):285-287.
30. Centers for Disease Control and Prevention. Recommendations for partner services programs for HIV infection, syphilis, gonorrhea, and chlamydial infection. MMWR. 2008;57(RR9):1-63.
31. Perinatal HIV Guidelines Working Group. Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Washington, DC: National Institutes of Health; 2012. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf. Last accessed March 14, 2014.
32. Centers for Disease Control and Prevention. HIV and Its Transmission. Available at http://www.hivlawandpolicy.org/sites/www.hivlawandpolicy.org/files/CDC%2C%20HIV%20and%20its%20transmission.pdf. Last accessed March 17, 2014.
33. National Institutes of Health, National Institute of Allergy and Infectious Diseases. Reassuring Findings About Infants Exposed to Zidovudine. Available at http://www.niaid.nih.gov/news/newsreleases/1999/pages/pactg219.aspx. Last accessed March 17, 2014.
34. Centers for Disease Control and Prevention. Surveillance of Occupationally Acquired HIV/AIDS in Healthcare Personnel, as of December 2010. Available at http://www.cdc.gov/HAI/organisms/hiv/Surveillance-Occupationally-Acquired-HIV-AIDS.html. Last accessed March 17, 2014.
35. Occupational Safety and Health Administration. Bloodborne Pathogens: Regulation 1910.1030. Available at https://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=10051. Last accessed March 17, 2014.
36. Kuhar DT, Henderson DK, Struble KA, et al. Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis. Infect Control Hosp Epidemiol. 2013;34(9):875-892.
37. Centers for Disease Control and Prevention. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the U.S. Department of Health and Human Services. MMWR. 2005;54(RR2):1-19.
39. Centers for Disease Control and Prevention. Hepatitis C Virus and HIV Coinfection. Available at http://www.cdc.gov/idu/hepatitis/hepc_and_hiv_co.pdf. Last accessed March 17, 2014.
40. Tierney LM, McPhee SJ, Papadakis MA (eds). Current Medical Diagnosis and Treatment. 46th ed. New York, NY: McGraw-Hill; 2006.
41. Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR. 2006;55(RR14):1-17.
42. U.S. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Last accessed November 12, 2014.
43. Reuters Health Information. New HIV Treatment Guidelines Focus on "Preferred" Regimens. Available at http://www.natap.org/2003/reuters/071803_1.htm. Last accessed March 17, 2014.
44. Centers for Disease Control and Prevention. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States, 2014: A Clinical Practice Guideline. Available at http://www.cdc.gov/hiv/pdf/prepguidelines2014.pdf. Last accessed November 12, 2014.
45. Boehringer Ingelheim. Important Safety Information: Intracranial Hemorrhage in Patients Receiving Aptivus (tipranavir) capsules. Available at http://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM153070.pdf. Last accessed March 17, 2014.
46. Chan-Tack KM1, Struble KA, Birnkrant DB. Intracranial hemorrhage and liver-associated deaths associated with tipranavir/ritonavir: review of cases from the FDA's Adverse Event Reporting System. AIDS Patient Care STDS. 2008;22(11):843-850.
47. U.S. Food and Drug Administration. FDA Approves New HIV Treatment for Patients Who Do Not Respond to Existing Drugs. Press Release. June 2006. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108676.htm. Last accessed March 17, 2014.
48. Roche Laboratories, Inc. Fuzeon. Available at http://www.fuzeon.com/Fuzeon/hcp-index.do. Last accessed March 17, 2014.
49. Montgomery JP, Mokotoff ED, Gentry AC, et al. The extent of bisexual behaviour in HIV-infected men and implications for transmission to their female sex partners. AIDS Care. 2003;15:829-837.
50. AIDSmeds.com. Trizivir. Available at http://www.aidsmeds.com/archive/Trizivir_1583.shtml. Last accessed March 17, 2014.
51. AIDSmeds.com. Combivir. Available at http://www.aidsmeds.com/archive/Combivir_1083.shtml. Last accessed March 17, 2014.
52. Yick A, Berthold SM. Conducting research on violence in Asian American communities: methodological issues. Violence and Victims. 2005;20(6):661-677.
53. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Atlanta, GA: Centers for Disease Control and Prevention; 2013. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Last accessed November 12, 2014.
54. Agency for Health Care Policy and Research. Many People with AIDS Change Their Minds About End-of-Life Care as the Disease Progresses. 1999. Available at http://archive.ahrq.gov/research/apr99/ra11.htm. Last accessed March 17, 2014.
55. Abercrombie P. Women living with HIV infection. Nursing Clinics of North America. 1996;31(1):97-105.
56. National Institute of Allergy and Infectious Diseases. HIV Infection in Women. Available at http://www.niaid.nih.gov/topics/hivaids/understanding/population%20specific%20information/pages/womenhiv.aspx. Last accessed March 17, 2014.
57. International Partnership for Microbicides. Why Microbicides? Available at http://www.ipmglobal.org/why-microbicides. Last accessed March 14, 2014.
58. Bartlett JG, Cheever LW, Johnson MP, Paauw DS (eds). Guide to Primary Care of People with HIV/AIDS. Washington, DC: U.S. Department of Health and Human Services; 2004.
59. Centers for Disease Control and Prevention. Fact Sheet: HIV Among Pregnant Women, Infants, and Children. Available at http://www.cdc.gov/hiv/risk/gender/pregnantwomen/facts/index.html. Last accessed March 14, 2014.
60. U.S. Preventative Services Task Force. Screening for HIV. Available at http://www.uspreventiveservicestaskforce.org/uspstf13/hiv/hivfinalrs.htm. Last accessed March 14, 2014.
61. Schiodt M. HIV-associated salivary gland disease: a review. Oral Surg Oral Med Oral Pathol. 1992;73:164-167.
62. Klasse PJ, Shattock RJ, Moore JP. Which topical microbicides for blocking HIV-1 transmission will work in the real world?PLoS Med. 2006;3(9):e351.
63. Schneider E, Whitmore S, Glynn MK, Dominguez K, Mitsch A, McKenna MT. Revised surveillance case definitions for HIV infection among adults, adolescents, and children aged <18 months and for HIV infection and AIDS among children aged 18 months to <13 years—United States, 2008. MMWR Recomm Rep. 2008;57(RR10):1-8.
64. Centers for Disease Control and Prevention. 1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR. 1994;43(RR12):1-10.
65. AIDS InfoNet. Fact Sheet Number 616: Older People and HIV. Available at http://www.aidsinfonet.org/fact_sheets/view/616. Last accessed March 14, 2014.
67. National Institute on Aging. HIV, AIDS and Older People. 2009. Available at http://www.nia.nih.gov/HealthInformation/Publications/hiv-aids.htm. Last accessed March 14, 2014.
68. Shelton DL. AIDS in the "golden years:" new challenges for doctors. American Medical News. 1999;42:29-30.
69. U.S. Food and Drug Administration. Press Release: FDA Approves Novel Antiretroviral Drug. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108960.htm. Last accessed March 13, 2014.
70. U.S. Department of Health and Human Services. Preventive HIV Vaccines. 2006. Available at http://aidsinfo.nih.gov/ContentFiles/HIVPreventionVaccines_FS_en.pdf. Last accessed March 17, 2014.
71. U.S. Department of Health and Human Services. Therapeutic HIV Vaccines. Available at http://aidsinfo.nih.gov/ContentFiles/Therapeutic_HIV_Vaccines_FS_en.pdf. Last accessed March 17, 2014.
72. American Academy of Pediatrics. Policy Statement: HIV testing and prophylaxis to prevent mother-to-child transmission in the United States. Pediatrics. 2008;122(5):1127-1134.
73. U.S. Food and Drug Administration. Press Release: FDA Approves New HIV Drug: Raltegravir Tablets Used in Combination with Other Antiretroviral Agents. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109008.htm. Last accessed March 13, 2014.
74. Rashad AM, MacVane Phipps F, Haith-Cooper M. Obtaining informed consent in an Egyptian research study. Nursing Ethics. 2004;11(4):394-399.
75. Centers for Disease Control and Prevention. Eliminating Perinatal HIV Transmission. Available at http://www.cdc.gov/primarycare/materials/hivtransmission/docs/hivtransmission.pdf. Last accessed March 17, 2014.
77. National Conference of State Legislatures. HIV/AIDS Facts to Consider: 1999. Denver: NCSL; 1999.
78. Bardi JS. Towards an AIDS Vaccine: TSRI Scientists Describe Unusual Antibody That Targets HIV. Available at http://www.scripps.edu/newsandviews/e_20030630/hiv.html. Last accessed March 17, 2014.
79. Ahn J, Cohen SM. Transmission of human immunodeficiency virus and hepatitis C virus through liver transplantation.Liver Transpl. 2008;14(11):1603-1608.
80. Reuters Health Information. Vaccine Failure Shows Long AIDS Fight Remains. Available at http://www.royalsociety.org.nz/2003/02/25/health-aids-vaccine-9/. Last accessed March 17, 2014.
81. U.S. Food and Drug Administration. Approval of Rapid INSTI[TM] HIV-1 Antibody Test. Available at http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm235483.htm. Last accessed March 12, 2014.
82. National Institute of Allergy and Infectious Disease. Scientific Updates: Global HIV Vaccine. Available at http://www.niaid.nih.gov/vrc/scientificupdates_hiv.htm. Last accessed March 17, 2014.
83. Centers for Disease Control and Prevention. Revised Surveillance Case Definition for HIV Infection—United States, 2014. Available at http://www.cdc.gov/hiv/pdf/policies_PRP_Revised_HIV_Case_Def.pdf. Last accessed March 14, 2014.
84. Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Rockville, MD: Department of Health and Human Services; 2014.
85. Centers for Disease Control and Prevention. Syringe Disinfection for Injection Drug Users. Available at http://www.cdc.gov/idu/facts/disinfection.pdf. Last accessed January 8, 2014.
86. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.N Engl J Med. 2010;363:2587-2599.
87. Carrese J, Rhodes L. Western bioethics on the Navaho reservation: benefit or harm? JAMA. 1995;274:826-829.
89. Carey RF, Herman WA, Retta SM, Rinaldi JE, Herman BA, Athey TW. Effectiveness of latex condoms as a barrier to human immunodeficiency virus-sized particles under the conditions of simulated use. Sex Transm Dis. 1992;19(4):230-234.
90. National Institutes of Health, National Institute of Allergy and Infectious Diseases. Workshop Summary: Scientific Evidence on Condom Effectiveness for Sexually Transmitted Disease (STD) Prevention. Available at http://www.niaid.nih.gov/about/organization/dmid/documents/condomreport.pdf. Last accessed March 17, 2014.
91. Centers for Disease Control and Prevention. Trends in HIV-related risk behaviors among high school students—United States, 1991–2011. MMWR. 2012;61(29):556-560.
92. Centers for Disease Control and Prevention. HIV/AIDS Prevention Research Synthesis Project. Available at http://www.cdc.gov/hiv/dhap/prb/prs/index.html. Last accessed February 11, 2014.
93. American Academy of Pediatrics Committee on Psychosocial Aspects of Child and Family Health and Committee on Adolescence. Sexuality education for children and adolescents. Pediatrics. 2001;108(2):498-502.
94. HIV/AIDS Epidemiology Unit, Public Health-Seattle and King County and the Infectious Disease and Reproductive Health Assessment Unit, Washington State Department of Health. HIV/AIDS Epidemiology Report, First Half 2013: Volume 82. Olympia, WA: Washington State Department of Health; 2013.
95. Washington State Legislature. Washington Administrative Code Chapter 246-101 Notifiable Conditions. Available at http://apps.leg.wa.gov/WAC/default.aspx?cite=246-101. Last accessed March 12, 2014.
96. Washington Department of Health. Summary of Washington State HIV/AIDS Reporting Requirements and Regulations. Available at http://www.kingcounty.gov/healthservices/health/communicable/hiv/epi/legal.aspx. Last accessed March 12, 2014.
97. Washington State Legislature. Washington Administrative Code Chapter 246-100 Communicable and Certain Other Diseases. Available at http://apps.leg.wa.gov/wac/default.aspx?cite=246-100. Last accessed March 12, 2014.
98. Revised Code of Washington. Chapter 70.24.330 HIV Testing-Consent, Exceptions. Available at http://apps.leg.wa.gov/rcw/default.aspx?cite=70.24.330. Last accessed March 12, 2014.
99. U.S. Food and Drug Administration. Truvada for PrEP Fact Sheet: Ensuring Safe and Proper Use. Available at http://www.fda.gov/downloads/NewsEvents/Newsroom/FactSheets/UCM312279.pdf. Last accessed March 17, 2014.
1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Bethesda, MD: U.S. Department of Health and Human Services; 2013. Summary retrieved from National Guideline Clearinghouse at http://www.guideline.gov/content.aspx?id=43783. Last accessed March 24, 2014.
2. U.S. Preventive Services Task Force. Screening for HIV. Available at http://www.uspreventiveservicestaskforce.org/uspstf/uspshivi.htm. Last accessed March 24, 2014.
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