Important note: Information in this article was accurate in November 2007. The state of the art may have changed since the publication date. 
Although HIV was first isolated in 1983, it has been very difficult to create a vaccine against this virus that would protect people. In part, this is because the immune system is not well understood, particularly in the tissues—anus, mouth, penis and vagina—that first encounter HIV. Moreover, this virus causes complex changes to the immune system that are difficult to undo. And, as researchers gain a more sophisticated understanding of the interaction between HIV and the immune system, the challenges that lie in the path for creating an effective vaccine seem daunting. So, for now, for sexually active people, practicing safer sex remains critical when it comes to limiting new HIV infections.
But safer sex is not universally practiced and HIV infection continues to spread in the high-income regions of North America and Western Europe. So some researchers are starting to consider using medicines to limit HIV infection.
One possibility is to use a relatively short course of anti-HIV medicines just after a person may have been exposed to HIV. This is called PEP—post-exposure prophylaxis— and the hope is that these medicines can hinder HIV’s ability to infect cells. By restricting HIV’s ability to spread, researchers hope that the immune system can contain the virus.
There have not been randomized, placebo-controlled trials to assess the effectiveness of PEP for HIV exposure in high-income countries, so most advice about it, particularly in cases of potential sexual exposure to HIV, comes from experiments on monkeys. In these experiments, many of which were done in the mid-to-late 1990s, researchers gave the anti-HIV medication tenofovir (Viread) to monkeys after they were infected with SIV—simian immunodeficiency virus. This virus can cause an AIDS-like disease in some monkeys.
The researchers found that giving monkeys tenofovir within 24 hours of exposure to SIV and continuing treatment for 28 consecutive days prevented SIV from spreading and taking hold. However, beginning tenofovir 72 hours or even as soon as 48 hours after exposure greatly reduced protection from SIV.
Based on these results, guidelines on HIV PEP for people encourage the use of anti-HIV medications within 72 hours (ideally within 24 hours) of exposure to HIV. This therapy should continue for 28 days.
Because of community interest in PEP, researchers at the University of California at Los Angeles (UCLA) conducted a study to assess its safety and determine whether it would get the interest and participation of people at high risk for HIV infection. The results of this six-month pilot project are promising and may encourage further research on PEP.
Researchers recruited participants who reported potential HIV exposure within 72 hours following sex with “persons known or suspected to be infected with HIV.”
The study team sought participants who were considered at high risk for contracting HIV infection because of engaging in the following:
Potential participants called a specified telephone number and were then referred to a local community clinic. Participants were interviewed, and those who consented were tested for HIV antibodies. Counselling was given both before and after testing. Participants then received their first dose of study medication. They were encouraged to return to the clinic to receive the full course of treatment to take home and to complete surveys, blood and urine tests and further counselling.
Researchers screened 287 callers who responded to advertisements about the study. Of these, only 100 were enrolled. Two people were later referred for care when HIV testing revealed that they were already infected. Here is the average profile of the participants:
The two most commonly used substances taken 30 days before entering the study were as follows:
The medications used in this study were the co-formulation (put into one tablet called Combivir) of two common drugs taken for the treatment of HIV infection, as follows:
Combivir was taken twice daily in this study.
Most participants disclosed that they had been tested for HIV some time in the past year.
The day of the week with the highest enrollment in the study was Monday. This suggests that exposure to HIV occurred on the weekend.
The majority of participants had what the study team described as “valid concerns for HIV exposure” because of unprotected high-risk sex “with individuals known or suspected to be HIV positive,” as follows:
A total of 23% of participants reported using condoms at the time of potential exposure and most of these reported what the researchers called “condom failure.”
Taking every dose of medication exactly as prescribed, day after day, is a behaviour called adherence. When it comes to treating HIV, high levels of adherence are required for effectiveness. Researchers found that about 35% of participants were not adherent to their medications.
About 77% of participants reported at least one side effect, usually mild in intensity, as follows:
One study volunteer reported thoughts about suicide after potential exposure to HIV and required hospitalization. The study team decided that these feelings were not linked to the medications used in the study.
Retaining a large proportion of the people who volunteered for this study was a difficult task for the study team. After the first week, when participants received enough medications to see them through 28 days of PEP, many stopped returning to the clinic. Indeed, by the sixth month of the study, only 49% of participants continued to visit the clinic. The researchers noted that this suggests that many participants were “interested mostly in obtaining their [anti-HIV medications] with only minor interest in behavioural risk counselling…”
By the end of the study, participants reported having fewer sexual partners and increasing degrees of certainty that they would “never have unsafe sex again.” Yet before, during and after the study they tended to report using condoms less than 50% of the time.
None of the participants who remained in the study for its duration (six months) became HIV positive. But it is possible that some of the participants who dropped out later tested positive. Because of this and other factors, the research team noted that it is not possible to assess the effectiveness of PEP based on the results of its study.
The findings from the LA study are limited because of several factors, including the following:
1. Participants in the study were mostly well-educated, self-identified gay men. They were efficient at interacting with the health care system and finding care quickly. As HIV is spreading to other, more marginalized populations, the experience of this study may not apply to them.
2. There were almost no people in this study who were exposed to HIV as a result of sharing contaminated needles. Researchers stated that perhaps outreach and recruitment were insufficient for attracting substance users. Another possibility they noted was that substance users who may have been exposed to HIV might not have sought PEP because of the effects of substance use or perhaps because of withdrawal symptoms.
3. The research team advertised its PEP study in Spanish and English and in areas of LA where people of colour live, plus a study site was located in a part of LA where Black and Hispanic people predominate. However, most of the study participants were white and recruited by a clinic located in a gay-identified neighbourhood. The reason for this difference in recruitment is not clear.
The LA study suggests that some people who experience a crisis—potential HIV exposure—can and will seek PEP. Future studies need to explore the integration of PEP (in cases of sexual exposure) into comprehensive HIV prevention programs. A major issue for such future programs is the question of who will pay for the cost of PEP in cases of HIV exposure resulting from sex or substance use.
REFERENCES:
1. Nishimura Y, Igarashi T, Haigwood NL, et al. Transfer of neutralizing IgG to macaques 6 h but not 24 h after SHIV infection confers sterilizing protection: implications for HIV-1 vaccine development. Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15131-6.
2. Milush JM, Stefano-Cole K, Schmidt K, et al. Mucosal innate immune response associated with a timely humoral immune response and slower disease progression after oral transmission of simian immunodeficiency virus to rhesus macaques. J Virol. 2007 Jun;81(12):6175-86.
3. Rollman E, Smith MZ, Brooks AG, et al. Killing kinetics of simian immunodeficiency virus-specific CD8+ T cells: implications for HIV vaccine strategies. J Immunol. 2007 Oct 1;179(7):4571-9.
4. Staprans SI, Barry AP, Silvestri G, et al. Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein. Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):13026-31.
5. Nilsson J, Boasso A, Velilla PA, et al. HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS. Blood. 2006 Dec 1;108(12):3808-17.
6. Tsai CC, Follis KE, Sabo A, et al. Prevention of SIV infection in macaques by (R)-9-(2-phosphonylmethoxypropyl) adenine. Science. 1995 Nov 17;270(5239):1197-9.
7. Tsai C-C, Emau P, Follis KE, et al. Effectiveness of postinoculation (R)-9-(2-phosphonylmethoxypropyl) adenine treatment for prevention of persistent simian immunodeficiency virus SIVmne infection depends critically on timing of initiation and duration of treatment. J Virol. 1998 May;72(5):4265-73.
8. Lavoie E, Alary M, Remis RS, et al. Determinants of HIV Seroconversion Among Men Who Have Sex With Men Living in a Low HIV Incidence Population in the Era of Highly Active Antiretroviral Therapies. Sex Transm Dis. 2007 Sep 13; [Epub ahead of print].
9. Shoptaw S, Rotheram-Fuller E, Landovitz RJ, et al. Non-occupational post-exposure prophylaxis as a biobehavioral HIV-prevention intervention. AIDS Care 2008; in press.
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