Prevention Updates from CROI
Suppression of genital herpes, circumcision, and serosorting as prevention
by Keith R. Green
Suppression of genital herpes may not prevent HIV infection after all
A study presented at CROI 2008 found that suppressing HSV-2 (also known as genital herpes) with a currently available therapy was not effective at preventing HIV seroconversion among participants.
The study enrolled large numbers of heterosexual women from Africa and men who have sex with men (MSM) from the U.S. and Peru (3,277 participants in total), who were all HIV negative but positive for HSV-2. Participants were randomized into two different groups, with one group receiving a standard treatment for HSV-2 (400 mg of acyclovir twice daily) and the other receiving a placebo (or dummy pill), and then followed for 18 months.
Aside from receiving their study drugs during routine monthly visits, participants were given adherence and risk reduction counseling and were tested for HIV on a quarterly basis.
There was no significant difference found in HIV incidence between the two groups, with participants in the acyclovir arm actually experiencing a slightly higher incidence rate than those receiving placebo (75 events versus 64, respectively). Reported and observed adherence between the two groups was relatively high, ruling adherence out as a possible cause for the unexpected outcome.
Overall reduction of genital ulcer disease (GUD) associated with HSV-2 was reduced by 35 percent in the acyclovir arm, leading researchers to conclude that the drug is effective at suppressing HSV-2 but not at preventing HIV in those infected.
Connie Celum M.D., a researcher at the University of Washington who presented the study at CROI, explained that these findings are “surprising, disappointing, and important results for HIV prevention,” and that they “underscore why it is important to do clinical trials to move from epidemiological data.”
Celum suggested, as a possible interpretation of the data, that perhaps HSV-2 is not the risk factor for HIV that we have come to believe it is. Given the plethora of data to the contrary however, which estimates that 38-69% of new HIV infections in men and 8-49% in women are due to prevalent HSV-2, she contends that this conclusion is highly unlikely.
She goes on to suggest that “there is [also] a possibility that we have underestimated HSV-2 in terms of the frequency of reactivation, based on some recent studies, as well as the potential importance of the genital immune response. [This leads] to the possibility that we need either higher doses [of the drugs that we are currently using to suppress HSV-2], new drugs, or combination therapy.”
Circumcision also decreases the risk of HSV-2 infection in men, as well as other STIs in their female partners
Recent studies have proven the effectiveness of circumcision in preventing HIV infection, particularly among heterosexual men in African countries. Building on that knowledge, data was presented at CROI 2008 on a study that was conducted to explore the effect of the procedure on HSV-2 acquisition in heterosexual men and vaginal infections among their female partners.
Nearly 2,800 HSV-2-negative men were randomized into two groups, one group receiving immediate circumcision and the other receiving the procedure later in the study. Both groups were followed for two years.
Subsequently, more than 1,600 of the wives of the participating men were recruited and randomized into two groups, depending on when their husband was circumcised in the trial.
The overall incidence of HSV-2 infection decreased by 25% in men who were circumcised immediately, compared to those whose circumcision was delayed. Moreover, there was a 50% reduction in men who reported consistent condom use.
For the women, there was a significant decrease in reported genital ulcer disease (GUD), and a significant reduction in trichomonas (about 50% for those who were married to men who were circumcised immediately). Significant decreases in bacterial vaginosis were also observed.
Researchers concluded that male circumcision is also effective at preventing infection with HSV-2 in men, and further reduces rates of sexually transmissible infection in their female partners. These effects of circumcision may have an impact on the protective effect of the procedure on HIV acquisition.
Serosorting decreases risk for HIV infection, but not seropositioning
Serosorting and seropositioning have become buzz words in HIV prevention in the U.S., particularly as it relates to men who have sex with men (MSM). With increasing rates of HIV infection among this population, however, the effectiveness of such practices remains questionable.
Looking at data from more than 3,000 participants in the EXPLORE study, a randomized trial of an individual behavioral HIV intervention in HIV-negative men who have sex with men in the U.S., researchers were able to ascertain that a sizable minority of MSM in all demographic categories do in fact engage in these practices.
They found that the most common of the two practices among those surveyed was serosorting, defined in this study as the preferential use of condoms with partners whose HIV status was either positive or unknown. Serosorting was associated with a 12% decrease in risk for HIV seroconversion, even in those reporting 10 or more sex partners.
Seropositioning, however, which is defined as the practice of insertive rather than receptive anal sex with a partner whose HIV status is either positive or unknown (which may or may not include the use of condoms), was less common and significantly less effective. In fact, researchers found no evidence that seropositioning had any effect against HIV acquisition.
A separate poster session at CROI presented data from a study of HIV serosorting practices among HIV-negative gay and bisexual men in the San Francisco Bay area. This study supported the notion that serosorting practices were common among both Bay area residents in general and among circuit party attendees (with more of the circuit party attendee participants reporting that they were more likely to have practiced serosorting than those in the general population).
Serosorting, however, was defined differently in this study than the above one. Participants, who were all HIV-uninfected, were asked if their decision to have sex with a potential partner was impacted by his HIV status. This definition is consistent with the traditional use of the term, which basically means selecting sexual partners of like serostatus.
The take-home message, offered by Susan Philip of the San Francisco Department of Public Health who presented the EXPLORE study data, is to continue to promote condom use among MSM, in support of serosorting as an effective HIV prevention strategy. Philip also pointed out that promoting frequent HIV testing among MSM and ensuring that access to the most advanced testing technology is available is also critical.