Prevention—what doesn’t work?

In a session entitled “Status of the U.S. HIV/AIDS Epidemic: Is It Changing and If Not, Why Not?” Harold Jaffe, MD, former head of the CDC, discussed a not-yet-published review of behavioral modification studies employing abstinence-only approaches. None of the eight randomized studies demonstrated that encouraging abstinence alone caused a decrease in self-reported risk behaviors or in incidence of pregnancy or sexually transmitted infections (STIs). Abstinence counseling definitely has a place in a comprehensive prevention education program, but it should not be used as a stand-alone strategy.

Prevention—what works?

It is worth noting a couple of significant successes in slowing the HIV epidemic. Testing donated blood has lowered the rate of HIV-infected units from one in 100 units in the early 1980s to approximately one in 2 million today.

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Condoms, consistently and properly used, profoundly decrease the risk of HIV transmission. However, they do not reliably prevent other STIs, e.g., those of herpes simplex virus and human papillomavirus, or syphilis, all of which can be transmitted by skin-to-skin contact. Moreover, the presence of STIs like HSV and syphilis, even when subclinical, facilitates HIV transmission.

Appropriate use of antiretroviralsUse of antiretrovirals during pregnancy and intrapartum has dramatically reduced mother-to-child transmission (MTCT); comparing the years 1990-1992 with 1999-2000, the rate of MTCT decreased from 18.1% to 1.6%.3 It makes sense that controlling patients’ viral load by using highly active antiretroviral therapy (HAART) would impede transmission.

However, the viral load in the blood—even one that is “nondetectable”—does not necessarily reflect viral kinetics in sexual fluids. One Dutch study provides evidence that HAART has attenuated an overall increase in new HIV diagnoses since 1996 in the Netherlands.4 However, while treating chronically infected individuals who lack evidence of serious immunodeficiency or a very high viral load might make sense from a public-health standpoint, this has not been demonstrated to provide clinical benefit to individual patients and will expose them to longer courses of potentially toxic treatment.

The role of herpes simplex virus

A few studies have examined the effects of treating herpes simplex virus type 2 (HSV-2) on HIV viral load and transmission. In one randomized, double-blind, placebo-controlled South African study involving 300 women with HIV and HSV-2 infection, acyclovir 400 mg b.i.d. decreased HIV load in serum and cervicovaginal fluid.5 Participants were not on HAART. In a similar study, 67 Thai women infected with HIV/HSV-2 and not receiving HAART were randomized to acyclovir 800 mg b.i.d. vs. placebo.6

Acyclovir recipients had significantly lower HIV load in serum and cervicovaginal fluid. Another Thai study took the next step and showed that women who were shedding HSV-2 DNA in cervicovaginal fluid at the time of delivery were significantly more likely to transmit HIV intrapartum; six of 21 shedders (28.6%) transmitted HIV to their babies compared with 22 of 260 (8.5%) non-shedders.7 Women who were shedding HSV-2 DNA during gestation had statistically higher HIV load in plasma and cervicovaginal fluid.

These studies are intriguing in that they provide more evidence of the deleterious effects of co-infection with HIV and HSV-2. Some clinicians now routinely discuss screening for HSV-2 antibodies with their HIV patients, including those who have never had any clinical manifestations of herpes. Treating HSV-2 infection, even when it is subclinical, may have an effect on HIV transmission and pathogenesis.

Circumcision is helpful

We now have clear evidence from multiple African studies that male circumcision decreases acquisition of HIV. A Ugandan study compared the effects of immediate vs. delayed circumcision (24 months later) on HIV acquisition.Researchers recruited almost 5,000 HIV-negative men and randomized half to each treatment arm. HIV incidence was reduced by more than 50% among those who were circumcised at baseline. Those patients also experienced less genital-ulcer disease.8,9 These findings have prompted the New York City Department of Health to consider promoting circumcision as an HIV prevention strategy. While it is unclear at this point if uncircumcised American men will embrace this suggestion, one survey by the CDC hints that a significant proportion would not dismiss the idea out of hand. MSM in five different cities were asked if they would be willing to undergo circumcision if it were proven to reduce HIV infection. While only 20% of respondents were uncircumcised, >50% (45 of 84) were willing to undergo the procedure if it would protect them from HIV infection.10 It should be emphasized that circumcision would by no means eliminate the possibility of sexual transmission of HIV.