Each year, about 50,000 patients in the United States are infected with HIV, with most transmissions occurring through sexual contact among men who have sex with men (MSM), a designation that includes transgender women. Effective antiretroviral therapy has stabilized HIV incidence since the late 1990s; however, the demographics of individuals acquiring HIV have changed, with the highest incidence among young black MSM. Similarly, transmission among heterosexuals now accounts for almost one-third of new infections and also predominantly occurs among black and Hispanic ethnic minorities.1 HIV prevention options have expanded, resulting in a more complex and increasingly patient-centered field. Providers must be prepared to recommend prevention options that are effective and to which patients can adhere.
HIV prevention begins with routine screening; patients must be aware of their HIV status to determine and employ appropriate steps to prevent HIV transmission. Abstinence, monogamy, and condoms have long been the cornerstone of HIV prevention, and continue to play an important role. Antiretroviral drugs are increasingly recognized for their role in HIV prevention. HIV-positive patients taking antiretroviral therapy reduce their risk of sexual and perinatal transmission. HIV-negative patients may benefit from antiretrovirals as preexposure prophylaxis (PrEP), or after potential exposure as postexposure prophylaxis (PEP). Vaccines and topical microbicides may provide additional options, as these emerging technologies come to market.
About 20% of people living with HIV/AIDS in the United States are unaware of their HIV status.1 Evidence suggests that people who are aware of their HIV-positive status are less likely to transmit HIV because of behavioral changes and initiation of antiretroviral therapy. One study reported a 57% reduction in unprotected anal and vaginal intercourse in HIV-positive patients who were aware of their status versus those unaware of their status.2
The CDC recommends:
* routinely screening all persons ages 13 to 64 years for HIV on an opt-out basis as a normal part of medical care
* including HIV screening in the routine panel of prenatal screening tests for all pregnant women3
* routinely screening all persons with tuberculosis (TB) for HIV. This includes patients starting treatment for TB and anyone with active TB disease or latent TB infection. Routine testing is also recommended for persons suspected of having TB and for contacts of patients with TB.4
* routinely screening all persons seeking treatment for sexually transmitted infections (STIs), including all patients attending STI clinics. Patients should be screened routinely for HIV during each visit for a new complaint.
* screening all persons likely to be at high risk for HIV at least annually. Persons at high risk include injection drug users and their sexual partners, persons who exchange sex for money or drugs, sexual partners of HIV-positive persons, and persons who themselves or whose sexual partners have had more than one sexual partner since their most recent HIV test.3
* testing MSM with additional risk factors (as noted in the previous bullet) every 3 to 6 months.5
Routinely taking an appropriate sexual history is essential to determine a patient's risk factors for HIV.6 The American Academy of Physician Assistants endorses routine screening, education, and counseling of patients on their individualized risk of HIV infection, and supports the CDC recommendations for incorporating routine screening into clinical practice.7
ABC'S (ABSTINENCE, BE MONOGAMOUS, AND CONDOMS)
Abstinence is the only method of eliminating the risk of sexual exposure to HIV but is not universally realistic, and focusing on abstinence-only prevention does not prepare patients for condom use or other HIV prevention.8 Monogamy with an HIV-negative partner reduces risk of exposure to HIV; however, a partner's sexual exclusivity cannot be ensured. Condoms appropriately used during oral, vaginal, and anal intercourse provide a barrier to HIV, but are often perceived as unavailable or unacceptable.9 Receptive condoms (“female condoms”) are controlled by the receptive partner and provide comparable protection against HIV and STIs to the standard insertive (“male”) condom.10 Condoms aren't always used and can inhibit sexual satisfaction by causing reduced sensation or loss of erection, and condom use cannot always be negotiated between sexual partners.11 Despite the wide availability and relatively low cost of condoms, in studies, 11% to 23% of HIV-positive individuals self-reported engaging in unprotected vaginal or anal intercourse in the previous 6 months, typically with a main partner.12 HIV prevention must extend beyond the limited scope of ABCs to reduce transmission incidence.
TREATMENT AS PREVENTION
Effective antiretroviral therapy reduces the risk of sexual HIV transmission through a reduction in HIV viral load. Antiretroviral therapy reduces HIV viral replication and allows for maintenance or recovery of the immune system, thus reducing the risk of the patient developing symptoms, opportunistic infections, and some malignancies. Global clinical trials of mostly male-female, serodiscordant couples (couples in which one partner is HIV-positive and one partner is HIV-negative) have shown up to a 96% reduction in risk of HIV transmission when the HIV-positive partner initiates antiretroviral therapy.13,14 Guidelines recommend offering antiretroviral therapy to patients at risk for transmitting HIV to sexual partners (Table 1); however, providers must take a patient-centered approach toward initiating antiretroviral therapy.15
PREVENTING MATERNAL-CHILD TRANSMISSION
Maternal-child transmission of HIV can occur during pregnancy, birth, or during breast-feeding. This type of transmission is the most common cause of HIV infection among children, resulting in infection of an estimated 162 children in 2010 in the United States.16 Perinatal transmission occurs at a rate of about 25%.17 Zidovudine given to the mother intragestationally and intrapartum, and to the infant for 6 months postpartum prevents transmission in 67% of infants.18 In the United States, the number of children under age 13 years diagnosed with AIDS has decreased from 855 in 1992 to 23 in 2010 due to routine screening of pregnant women and prevention of maternal to child transmission with available, effective antiretroviral therapy.16
All HIV-positive pregnant women, regardless of viral load and CD4 counts, should receive combination antiretroviral therapy for their health and to prevent HIV transmission. Women with a detectable viral load should be scheduled for delivery by cesarean section at 38 weeks if their HIV RNA is greater than 1,000 copies/mL, and should have IV antiretroviral drugs at the time of delivery if their HIV RNA is greater than 400 copies/mL. HIV-exposed infants should be started on antiretroviral drugs as soon as possible following birth. Breast-feeding is not recommended for HIV-positive women, including those on antiretroviral therapy.19 The US Department of Health and Human Services guidelines contain the most current information on prescribing antiretroviral drugs to reduce the risk of perinatal transmission.20 Free clinical consultation on all aspects of perinatal HIV care is available by contacting the National Perinatal HIV Hotline at 1-888-448-8765.
When the risk of potential HIV exposure outweighs the potential for toxicity from antiretroviral drugs, PEP is administered to reduce the risk of seroconversion (Table 2). Expert consultation is recommended and available 24 hours a day by contacting PEPline at 888-448-4911.21
Occupational acquisition of HIV is rare, with only 57 confirmed cases and an additional 143 possible cases between 1981 and 2010 in the United States.22,23 Although transmission most commonly occurs through percutaneous injury with a known HIV-positive source patient, consistent use of universal precautions, protective equipment, and safety devices remains the most effective way of preventing occupational HIV exposure. When a potential exposure occurs, providers must know when and how to initiate and manage PEP. Of the reported cases of occupation acquisition of HIV, PEP failed in 14% of cases.21
PEP is also used for nonoccupational exposure to HIV, such as potential exposure related to sexual encounters or IV drug use. Randomized, controlled clinical trials have not been conducted due to feasibility and ethical considerations; however, observational studies have shown the potential for nonoccupational PEP (also called nPEP) to be effective.24
The CDC guidelines recommend HIV testing at baseline and prompt initiation (within 72 hours of exposure) of a 28-day course of combination antiretroviral drugs for patients at substantial risk (Table 3). Nonoccupational PEP is not recommended for patients who present with no or negligible risk of exposure or more than 72 hours after exposure. When the exposure source is of unknown HIV status, a clinical determination is made based on the perceived risk of the source being HIV-positive and the level of risk of exposure. Clinicians with little or no experience should consult an infectious diseases or HIV care specialist. Patients presenting with concern of HIV exposure should be counseled on HIV prevention and provided recommended prevention methods including condoms.25
Oral preexposure prophylaxis (PrEP) using antiretroviral drugs is a prevention strategy for HIV-negative patients to reduce the risk of acquiring HIV. The combination of 200 mg emtricitabine and 300 mg tenofovir (TDF/FTC) was recently approved by the FDA for prevention of sexual transmission of HIV. Daily oral TDF/FTC is 44% effective in reducing risk of HIV acquisition among MSM, and in one trial was 62.6% effective in reducing HIV acquisition among heterosexual men and women.26,27 Among heterosexual, serodiscordant couples, tenofovir (300 mg daily) and TDF/FTC reduced HIV acquisition by 67% and 75% respectively.28 In each trial of PrEP, trends toward higher efficacy were noted in participants who were the most adherent. However, randomized controlled trials designed to determine efficacy of daily TDF/FTC have been unable to demonstrate efficacy among women.29,30 The cause of this differing result is under investigation. PrEP demonstration projects are ongoing to explore the use of PrEP outside of a clinical trial setting and to assess longer-term drug profiles. Also, in a clinical trial in which most doses were given under direct observation, tenofovir reduced HIV acquisition by 48.9% among IV drug users.31
The CDC has released guidance for use of TDF/FTC for HIV prevention (Table 4).32–34 The guidance stresses the importance of adherence counseling, safer sex counseling, and condom use alongside administration of PrEP. For IV drug users, the CDC recommends daily TDF/FTC; however, the FDA indication for PrEP is limited to use for sexual exposure.
Microbicides are substances delivered topically to help diminish the risk of HIV transmission sexually in the case of condom slippage or tear. These substances act as an additional preventative measure, and can be used by patients who do not use condoms for the reasons described earlier. Development has focused on antiretroviral drugs delivered as gels or intravaginal rings.
In a clinical trial of African women, 1% tenofovir gel dosed before and after vaginal intercourse was 39% effective in reducing HIV acquisition. Analysis suggested a trend towards 54% effectiveness in the most adherent women. No major safety concerns were associated with 1% tenofovir gel, and no HIV resistance was seen among participants who seroconverted.35 A later trial was unable to show that daily use of 1% tenofovir gel could prevent HIV infection, although participants demonstrated low levels of adherence.30 An investigational non-nucleoside reverse transcriptase inhibitor, dapivirine, has been shown to be safe and tolerable when delivered through an intravaginal ring, and is being tested in a Phase 3 efficacy study.36
Receptive anal intercourse carries a several-fold increased risk of HIV infection compared with vaginal intercourse.37 Commercial lubricant is often used during anal intercourse, and consequently, a rectal microbicide gel may be a highly acceptable method of prevention.38 A clinical trial of 1% tenofovir gel applied rectally resulted in a high concentration of drug in the rectum; daily application conferred protection against HIV infection in laboratory testing; however, trial participants found the vaginal formulation to be poorly tolerated when used rectally.39 A later trial of reformulated tenofovir gel was safe, well tolerated, and has advanced into Phase 2 testing.40
Prophylactic HIV vaccines remain in early stages of development due to the inability of the human body to create a neutralizing antibody against HIV and viral diversity due to frequent mutation of HIV. Rapid viral integration into T cells following infection also limits the opportunity for a vaccine to act. A major prophylactic vaccine trial in Thailand showed a modest efficacy of 31% among men and women at largely heterosexual risk of transmission.41 Although this partially effective vaccine will likely not serve as a public health control measure for HIV, it represents the first significant result for this strategy.
African trials of circumcision among heterosexual men showed about a 60% reduction in acquisition of HIV among male participants.42–44 However, male circumcision is ineffective in reducing transmission from HIV-positive men to their female partners.45 Male circumcision may indirectly benefit females by reducing the HIV prevalence in the male population. The evidence for circumcision reducing HIV acquisition among MSM is weak and inconsistent. Some trials have shown a potential reduction of HIV acquisition among circumcised MSM who predominantly engage in the insertive role during anal intercourse.46 However, the potential for increased risk-taking due to this perceived protection offsets the benefit of circumcision.46
An understanding of current and emerging HIV prevention options lets patients and their healthcare providers create a patient-centered prevention plan. Providers should be prepared to empower patients with HIV prevention options based on the individual patient's risk, and should be willing to provide or refer patients for counseling and condoms. Testing following CDC guidelines and linking HIV-positive patients to medical care can improve outcomes for patients unknowingly living with HIV and increase prevention opportunities. Familiarity with ways to prevent maternal-child HIV transmission and the roles of circumcision, PEP, and nPEP can help prevent infection among patients with increased risk of HIV exposure. TDF/FTC provides an additional tool for prevention among MSM, at-risk heterosexually active adults, and IV drug users, and should be used in conjunction with other safer sex practices. Emerging biomedical methods of HIV prevention including microbicides and vaccines will expand available options.
2. Marks G, Crepaz N, Janssen RS. Estimating sexual transmission of HIV from persons aware and unaware that they are infected with the virus in the USA. AIDS. 2006;20(10):1447–1450.
3. Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55(RR-14):1–17.
4. Centers for Disease Control and Prevention. Controlling tuberculosis in the United States: recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America. MMWR. 2005;54(No. RR-12).
5. Finlayson TJ, Le B, Smith A, et al. HIV risk, prevention, and testing behaviors among men who have sex with men—National HIV Behavioral Surveillance System, 21 U.S. cities, United States, 2008. MMWR Surveill Summ. 2011;60(14):1–34.
6. Jennings P, Bachmann L. Yes, the sexual history is important. JAAPA. 2005;18(12):70–71.
7. American Academy of Physician Assistants. Position Paper: HIV Prevention. JAAPA. 2008;21(8):51–52.
8. Johnson BT, Scott-Sheldon LJ, Huedo-Medina TB, Carey MP. Interventions to reduce sexual risk for human immunodeficiency virus in adolescents: a meta-analysis of trials, 1985–2008. Arch Pediatr Adolesc Med. 2011;165(1):77–84.
9. Lytle D, Rouston L, Seabon G, et al. An in vitro evaluation of condoms as barriers to a small virus. sexually transmitted diseases. Sexually Transmitted Diseases. 1996;24(3):161–164.
10. Minnis AM, Padian NS. Effectiveness of female controlled barrier methods in preventing sexually transmitted infections and HIV: current evidence and future research directions. Sexually Transmitted Infections. 2005;81(3):193–200.
11. Lammers M, Davidovich U, Prins M, Stolte I. Condom-induced erectile dysfunction (COINED): a unique predictor of deliberate sexual risk. 17th International AIDS Conference. Mexico City, 2008.
12. Morin SF, Myers JJ, Shade SB, et al.Predicting HIV transmission risk among HIV-infected patients seen in clinical settings. AIDS Behav. 2007;11(5 Suppl):S6–S16.
13. Donnell D, Baeten JM, Kiarie J, et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet. 2010;375(9731):2092–2098.
14. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. New Engl J Med. 2011;365(6):493–505.
17. De Cock KM, Fowler MG, Mercier E, et al.Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice. JAMA. 2000;283(9):1175–1182.
18. Connor EM, Mofenson LM. Zidovudine for the reduction of perinatal human immunodeficiency virus transmission: pediatric AIDS Clinical Trials Group Protocol 076—results and treatment recommendations. Pediatr Infect Dis J. 1995;14(6):536–541.
19. Perinatal HIV Guidelines Working Group. Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. 2006;12:65.
20. US Department of Health and Human Services. Panel on Treatment of HIV-Infected Pregnancy Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf
. Accessed March 10, 2013.
21. Panlilio AL, Cardo DM, Grohskopf LA, et al. Updated US Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep. 2005;54(RR-9):1–17.
22. Do AN, Ciesielski CA, Metler RP, et al. Occupationally acquired human immunodeficiency virus (HIV) infection: national case surveillance data during 20 years of the HIV epidemic in the United States. Infect Control Hosp Epidemiol. 2003;24(2):86–96.
24. Harrison L, Do Lago R, Moreira R, et al.Post-sexual-exposure chemoprophylaxis (PEP) for HIV: a prospective cohort study of behavioral impact. The 8th Conference on Retroviruses and Opportunistic Infections. Chicago, Illinois. 2001.
25. Smith DK, Grohskopf LA, Black RJ, et al. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the US Department of Health and Human Services. MMWR Recomm Rep. 2005;54(RR-2):1–20.
26. 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(27):2587–2599.
27. Thigpen M, Kebaabetswe P, Smith D, et al. Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 study. Sixth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Rome, 2011.
28. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367(5):399–410.
29. Van Damme L, Corneli A, Ahmed K, et al.The FEM-PrEP trial of emtricitabine/tenofovir disoproxil fumarate (Truvada) among African women. 19th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, 2012.
30. Marrazzo J, Ramjee G, Nai G, et al.Pre-exposure Prophylaxis for HIV in Women: Daily Oral Tenofovir, Oral Tenofovir/Emtricitabine, or Vaginal Tenofovir Gel in the VOICE Study (MTN 003). 20th Conference on Retroviruses and Opportunistic Infections. Atlanta, GA, 2013.
31. Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet. 2013;381(9883):2083–2090.
32. Centers for Disease Control and Prevention. Interim guidance: preexposure prophylaxis for the prevention of HIV infection in men who have sex with men. MMWR. 2011;60(3):65–68.
33. Centers for Disease Control and Prevention. Interim guidance for clinicians considering the use of preexposure prophylaxis for the prevention of HIV infection in heterosexually active adults. MMWR
34. Smith DK, Martin M, Lansky A, et al. Update to interim guidance for preexposure prophylaxis (PrEP) for the prevention of HIV infection: PrEP for injecting drug users. MMWR. 2013;62(23):463–465.
35. Karim QA, Karim SSA, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010;329(5996):1168–1174.
36. Nel A, Smythe S, Young K, et al. Safety and pharmacokinetics of dapivirine delivery from matrix and reservoir intravaginal rings to HIV-negative women. J Acquired Immune Deficiency Syndromes. 2009;51(4):416–423.
38. Carballo-Dieguez A, Stein Z, Saez H, et al. Frequent use of lubricants for anal sex among men who have sex with men: the HIV prevention potential of a microbicidal gel. Am J Public Health. 2000;90(7):1117–1121.
39. Anton PA, Cranston RD, Kashuba A, et al. RMP-02/MTN-006: a phase 1 rectal safety, acceptability, pharmacokinetic, and pharmacodynamic study of tenofovir 1% gel compared with oral tenofovir disoproxil fumarate. AIDS Res Human Retroviruses. 2012;28(11):1412–1421.
40. McGowan I, Hoesley C, Andrew P, et al. MTN-007: a phase 1 randomized, double-blind, placebo-controlled rectal safety and acceptability study of tenofovir 1% gel. 19th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, 2012.
41. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361(23):2209–2220.
42. Auvert B, Taljaard D, Lagarde E, et al. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 trial. PLoS Med. 2005;2(11):1112–1122.
43. Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet. 2007;369(9562):657–666.
44. Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet. 2007;369(9562):643–656.
45. Wawer MJ, Makumbi F, Kigozi G, et al. Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet. 2009;374(9685):229–237.
46. Templeton DJ, Millett GA, Grulich AE. Male circumcision to reduce the risk of HIV and sexually transmitted infections among men who have sex with men. Curr Opin Infect Dis. 2010;23(1):45–52.
HIV-1; antiretroviral; preexposure prophylaxis; postexposure prophylaxis; microbicide; vaccine
© 2013 American Academy of Physician Assistants.