The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Correspondence: Myron S. Cohen, MD Director, UNC Institute of Global Health and Infectious Disease Chief, Division of Clinical Infectious Diseases, 130 Mason Farm Road, Suite 2115, CB #7030 UNC Chapel Hill, Chapel Hill, NC 27514. E-mail: email@example.com.
Received for publication July 15, 2008, and accepted September 25, 2008.
In this issue of Sexually Transmitted Diseases, Du Mont et al.1 described a study of 318 adolescent females seeking care for sexual assault in Ontario, Canada. The study focuses on HIV prevention after sexual assault and produced findings consistent with earlier studies2: although the majority of women were eligible for postexposure prophylaxis (PEP), most (57%) chose not to initiate therapy, and only a third actually completed a course of therapy.
How can we account for the poor performance of this intervention? By any measure, the young women in this study seem highly motivated to protect their health. Indeed, they all sought health care after an assault. In their analysis, the investigators noted a number of factors, which made study subjects more likely to choose ART, such as a high level of anxiety (OR, 4.6) and student status (OR, 2.21). The most important influencing factor, however, was directive action (strong support for PEP) from the health care provider (OR 5.6). But 70% of the time, the healthcare provider was neutral (noncommittal) about PEP even though 84% of the subjects were eligible for treatment. Of those eligible, 94% were offered PEP.
These results suggest that the problem with PEP lies as much with the providers as the patients who are victims of assault. In most instances, providers are likely unsure about the value of PEP. This should come as no surprise since there are simply no human data to prove that HIV PEP works for sexual exposure nor is there research on how best to use it in humans. PEP guidelines were established based on research with rhesus macaques (reviewed in Ref.3). In the macaque model, vaginal HIV transmission occurs slowly4 or swiftly,5 depending on the details of exposure. Prophylaxis with tenofovir can reliably prevent infection in macaques if started promptly (less than 72 hours after exposure) and when continued for 28 days. These observations form the basis for HIV PEP protocol in humans. The only human randomized clinical trials data reflect the very visible success of PEP to prevent mother-to-child (postpartum) HIV transmission,6 but the biology of such transmission is simply far too different from sexual exposure to justify comparison. And clearly it is difficult, if not impossible, to make PEP cost-effective unless the intervention is limited to the highest risk groups,7 which is inconsistent with most guidelines. As a result, health care providers have received very mixed messages.
Sexual exposure to HIV in humans carries a very heterogeneous transmission probability.8 However, the risk is often conveyed as 1/1000 episode of intercourse, a number which clearly leads some victims to conclude that their risk of contracting HIV is low. But transmission probability rises dramatically during anal intercourse, or when genital tract viral load is high, or when inflammation or ulcers or traumatized tissues are present.4,8 These are largely “invisible” risks, undetectable during an assault, or even in the context of a prior relationship between victim and assailant. Indeed, the fact that subjects in the current report1 were less likely to chose ART if they knew their assailant for more than 24 hours is particularly alarming.
In this study of subjects who were given initial PEP, fully two thirds stopped therapy. Some subjects might have accurately determined that their risk was much lower than initially perceived, but it seems likely that most victims were bothered by the inconvenience and/or side effects of the treatment and concluded the risk was too low to justify it.
When health care providers believe that a history of possible HIV exposure justifies therapy, victims are best served when offered emergent, “front loaded” therapy and a follow-up when the victim is calmer. This is the strategy that seems to have been used in Ontario: a 4-day ART “starter-pack” and a follow-up visit.
The drug choices also matter. In the Ontario study, subjects received a 3-drug regimen of combivir and kaletra. Although studies have suggested that 2-drug PEP regimens are better tolerated,9 use of 3 drugs seems wise to prevent outgrowth of a resistant HIV variant, and such variants are certainly not rare.10 Drugs that get into the female genital tract at the highest concentration and with the greatest speed seem best suited for PEP.11
HIV PEP is here to stay, and preventing even a single case of HIV makes it well worthwhile.12 This study from Ontario, however, suggests the urgent need among health care providers for a different approach when counseling victims of rape. First and foremost, health care workers must be better educated about the risks of HIV transmission from even a single event, so that they themselves believe PEP is justified. Such education may be just as important as learning the drugs and their side effects, as was described in the Ontario study.1 Second, in the event of sexual assault, PEP should be administered emergently and with the best possible drugs. A more comprehensive discussion about PEP should occur after the victim has somewhat recovered from the attack. Third, if it is determined that PEP initiation is justified, the health care worker must work closely with the patient to ensure a complete a course of therapy. Adherence to PEP after occupational HIV exposure, although certainly imperfect, is often successful.13 Can we achieve the same results with victims of rape?
1. Du Mont J, Myhr TL, Husson H, et al. HIV post-exposure prophylaxis use among Ontario female adolescent sexual assault victims: A prospective analysis. Sex Transm Dis 2008; 35:973–978.
2. Roland ME. Postexposure prophylaxis after sexual exposure to HIV. Curr Opin Infect Dis 2007; 20:39–46.
3. Hosseinipour M, Cohen MS, Vernazza PL, et al. Can antiretroviral therapy be used to prevent sexual transmission of human immunodeficiency virus type 1? Clin Infect Dis 2002; 34:1391–1395.
4. Miller CJ, Li Q, Abel K, et al. Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J Virol 2005; 79:9217–9227.
5. Weiler AM, Li Q, Duan L, et al. Genital ulcers facilitate rapid viral entry and dissemination following intravaginal inoculation with cell-associated simian immunodeficiency virus SIVmac239. J Virol 2008; 82:4154–4148.
6. Kumwenda NI, Hoover DR, Mofenson LM, et al. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission. N Engl J Med 2008; 359:119–129.
7. Roland ME. Enhancing the potential benefits of HIV post-exposure prophylaxis. AIDS 2006; 20:1889–1890.
8. Powers K, Pettifor A, Poole C, et al. Systematic review and meta-analysis of the per-heterosexual-contact probability of HIV-1 transmission: Have the methods confused the message? Lancet. In press.
9. Bassett IV, Freedberg KA, Walensky RP. Two drugs or three? Balancing efficacy, toxicity, and resistance in postexposure prophylaxis for occupational exposure to HIV. Clin Infect Dis 2004; 39:395–401.
10. Little SJ, Frost SD, Wong JK, et al. Persistence of transmitted drug resistance among subjects with primary human immunodeficiency virus infection. J Virol 2008; 82:5510–5518.
11. Dumond J, Yeh R, Patterson KB, et al. Antiretroviral drug exposure in the female genital: Implications for oral pre- and post-exposure prophylaxis. AIDS 2007; 21:1899–1907.
12. Centers for Disease Control and Prevention. Antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV in the US: Recommendations from the US Department of Health and Human Services. MMWR Recomm Rep 2005; 54(RR-2):1–20.
13. Wang SA, Panlilio AL, Doi PA, et al. Experience of healthcare workers taking postexposure prophylaxis after occupational HIV exposures: Findings of the HIV Postexposure Prophylaxis Registry. Infect Control Hosp Epidemiol 2000; 21:780–785.