SAN FRANCISCO — Using nitrite inhalants, being uncircumcised, and engaging in certain sexual practices all increase the risk of HIV seroconversion among HIV-negative men who have sex with men, Dr. Susan P. Buchbinder reported at a meeting on HIV management sponsored by the University of California, San Francisco.
The results of her published study, along with related unpublished data, suggest a number of behavioral strategies to reduce the risk of HIV transmission among men who have sex with men (MSM).
“Some people say, 'We know what causes HIV [transmission], so why don't men change behavior?'” said Dr. Buchbinder, director of the university's HIV research section. “This is a response that one of my colleagues gave many years ago: She said, 'If behavior change were easy, I'd be thin.' I think we all recognize that behavior change is difficult. It's difficult to sustain over time. … We're trying to modify sexual risk and those are the kinds of behaviors that are often most difficult to change.”
Dr. Buchbinder's study involved 3,257 MSM from six U.S. cities who were HIV negative when they enrolled in the study in 1995. Participants were seen every 6 months for an 18-month period. During that time, 72 men became infected with HIV, yielding an annualized HIV seroincidence of 1.55 per 100 person-years (J. Acquir. Immune Defic. Syndr. 2005;39:82–9).
Taking into account the odds ratios of various risk factors (adjusted for sexual behaviors), as well as the prevalence of those risk factors in the population studied, Dr. Buchbinder and her colleagues calculated the population-attributable risks (PARs) of various behaviors and characteristics. (See table.)
The highest PARs were seen in men who had greater numbers of HIV-negative sex partners. The risk of seroconversion increased by 14% with each additional HIV-negative partner reported in the prior 6 months. Dr. Buchbinder explained this by noting that if one has a lot of HIV-negative partners, the chances increase that one of those partners may have recently become infected and is unaware of this.
These findings suggest that “we need to further develop new HIV-testing strategies, [such as] the implementation of rapid testing to allow people to know their serostatus more quickly,” she said.
The use of nitrite inhalants (known as poppers) also carried a high PAR in Dr. Buchbinder's published study. She mentioned other unpublished data that implicated other drugs, including crystal methamphetamine and sildenafil (Viagra).
“How is it that these substances augment the risk of acquiring HIV?” Dr. Buchbinder asked. “We can assume that for poppers and Viagra, [which are] often used in conjunction to enhance sexual pleasure, we might see an association with more anal sex. But in this study, we found that these three drugs were associated not just with having an increase in anal sex, and not even just having an increase in unprotected anal sex. [These men are] having an increase in unprotected anal sex with a partner whose serostatus was different.”
Furthermore, there are probably ways in which these drugs may enhance transmission biologically. For example, limited animal, in vitro, and human studies suggest that crystal methamphetamine is associated with increased HIV replication and perturbations in immune function.
Poppers are also associated with an effect on immune function as well as vasodilation in mucosal surfaces, which might facilitate transmission across those surfaces. And crystal methamphetamine, poppers, and Viagra may additionally be associated with more prolonged sexual activities, thereby increasing the risk of transmission across mucosal barriers.
It's difficult to know what to do about substance use in this population, Dr. Buchbinder said. Most studies on substance use address people who are addicted, and that model may not apply in a population that uses these drugs intermittently to enhance sexual pleasure. The few related studies on this population are limited by small numbers and short follow-up periods.
Another notable finding was that the risk of seroconversion was significantly higher in uncircumcised men, a finding that Dr. Buchbinder and her colleagues described as biologically plausible, with several possible mechanisms.
One somewhat surprising finding was the significant risk associated with receptive oral sex, even after controlling for receptive and insertional anal sex practices. Other studies have failed to find an independent contribution of receptive oral sex to HIV transmission. The investigators could not rule out the possibility that this apparent association may simply be a marker for riskier sex practices in general, or that it may reflect unmeasured confounders.
Although she acknowledged that behavior change is difficult to achieve, Dr. Buchbinder said that it's important not to give up.