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More Setbacks in HIV Prevention

Good prevention news was hard to find at the 15th Retrovirus Conference.

Last year’s Retrovirus Conference featured promising news about the protective effects of male circumcision (ACC Apr 2 2007). This year’s meeting, however, delivered more bad news than good in the field of HIV prevention.

Researchers described two new studies on male circumcision, both of which were nested within the larger circumcision study conducted in Rakai, Uganda. In the first study, circumcision of HIV-infected men with CD4 counts >350 cells/mm³ was not associated with a reduction in HIV transmission to their wives; in fact, if sex was resumed before wound healing was complete, circumcision was potentially associated with an increased likelihood of transmission [Abstract 33LB]. Rates of other sexually transmitted infections were similar between the wives of circumcised men and the wives of uncircumcised men. In the second study, circumcision of HIV-negative men was associated with an overall 20% decrease in the rate of acquisition of herpes simplex virus 2 [Abstract 28LB]. The protective effect was higher among men with multiple partners (30% reduction), those between the ages of 20 and 24 (40% reduction), and those who reported inconsistent condom use (50% reduction). Circumcision also was associated with reduced rates of genital ulcer disease, trichomoniasis, and bacterial vaginosis in the wives of study participants.

The much-awaited results of HPTN 039, a randomized, placebo-controlled trial of acyclovir suppressive therapy for the prevention of HIV acquisition, were also presented at the meeting [Abstract 32]. Unfortunately, HIV incidence was not different between the acyclovir and placebo arms (3.9 and 3.3 cases per 100 person-years, respectively). As could be expected, the incidence of genital ulcers was 37% lower in the acyclovir arm than in the placebo arm.

Investigators from the STEP study presented their results at a scientific meeting for the first time [Abstract 88LB]. As previously described (ACC Nov 19 2007), there was no evidence that the Merck adenovirus serotype 5 (Ad5) trivalent vaccine prevented HIV infection or that it lowered viral set point in those who became infected. In a new multivariate analysis, vaccination appeared to be associated with an increased risk for HIV acquisition among men with preexisting Ad5 immunity (hazard ratio, 3.1; 95% confidence interval, 1.5–6.5) and men who were not circumcised (HR, 4.5; 95% CI, 1.8–11.4).

The only promising prevention results presented at this meeting came from a prospective observational cohort study of the effects of vaginal Lactobacillus on genital viral load [Abstract 27LB]. Among 57 HIV-infected women, the acquisition of hydrogen peroxide–producing Lactobacillus resulted in a 0.7-log decrease in cervicovaginal lavage (CVL) HIV RNA, whereas the loss of such bacteria resulted in a 0.5-log increase in CVL HIV RNA. These findings underscore the importance of maintaining a healthy vaginal flora and suggest that Lactobacillus replacement should be explored as a prevention strategy.

Given all of these discouraging findings, one could reasonably conclude that the prevention field is in a state of "severe depression." Despite our best efforts, the past year has been characterized by the failure of various potential preventive measures — microbicides, diaphragms, vaccines, and acyclovir — in well-conducted, scientifically solid studies. However, we must put things in perspective: The therapeutic field was in a similar state of despair shortly after the 1993 International AIDS Conference in Berlin, and, just 3 years later, potent antiretroviral therapy became available. Many of us patiently await the results of the preexposure prophylaxis studies that are currently underway; such results could be available as early as next year.

— Carlos del Rio, MD

Published in AIDS Clinical Care March 10, 2008