We found significant independent associations between stimulant, popper and EDD use after adjusting for other important risk factors such as number of unprotected receptive anal sex partners among the 57 most recent HIV seroconverters in the MACS. Individually, these increased relative hazards for HIV seroconversion were 2.99, 3.89, and 3.44, respectively. However, among men who used all three drugs, the relative hazard escalated to 8 times that of men who reported no use of any of these three drug classes. Most notably, almost two-thirds of these recent seroconversions were associated with the use of these three drugs and approximately half of that AR remained even after taking into account the attributable risk associated with increasing numbers of unprotected receptive anal sex partners and other covariates of combination sex-drug use.
This paper extends the original findings of Plankey, et al.1
by incorporating all new HIV seroconversions through 2008 in the analyses, by examining a broader range of stimulants, by incorporating EDDs in the analyses and by assessing contributions of stimulants, EDDs and poppers, alone and in combination in predicting HIV seroconversion. Although the results from this study support the compounded risks for seroconversion with increasing number of types of sex-drugs found in previous studies 7, 21–23
to the best of our knowledge this is the first published longitudinal study that determined the magnitude of risk of recent HIV seroconversions attributable to the use of these three specific sex-drugs in all possible combinations.
Higher number of sex-drugs used may imply a rudimentary severity marker of behavioral disinhibition that also involves unprotected receptive anal sex with multiple partners. While identical percentages of HIV seronegative men and men who seroconverted (5%) reported use of EDDs, use of EDDs independently increased risk for HIV seroconversion. As the cohort ages, the potential for increased use of EDDs will likely rise among sexually active members of the MACS and with this increase, concomitant risks for continued HIV seroconversion, particularly among those who also report use of poppers and/or cocaine, crack or methamphetamine.
Our findings failed to detect a broad effect of all substance use on HIV seroconversion. In these analyses, severity of alcohol use at the current or previous visit contributed little to HIV seroconversion. Alcohol frequently is used to transact social and sexual connections24–26
, but sex-drugs can transcend this function and facilitate extreme forms of sexual behaviors.27, 28
While the use of self-reported behavioral data that measure associations between substance use and high risk sex pose significant methodological challenges, the design used by this study avoids some of the problems. The HIV seroconversion outcome was obtained objectively and precisely, and thus not subjected to misclassification. If the drug use and sexual practices or their concurrence were underreported by participants, the risks reported here are most likely conservative. Participants were not asked about sex-drug use with recent sexual partners (i.e., episodic data), which creates an inability to specify sex-drug use in the context of sexual events. But it remains a major strength of this study that it was performed within a natural history study of exposures ascertained consistently across the cohort and obtained prior to the seroconversion outcome.
Study limitations include a relatively small number of seroconversion events and limited numbers of participants in some of the cells. A consequence of these limitations is that some of the confidence intervals are fairly wide. Thus while some of the estimated hazard ratios could be somewhat smaller, from a public health perspective, we believe that our results are unambiguous.
Important questions remain as to whether and how vasoactive sex-drug use increases the likelihood of HIV infection through unprotected anal sex, even when the behavioral disinhibiting effects of drug use are taken into account. With the findings reported here, it is increasingly clear that combination sex-drug-usage contributes significantly to the spread of HIV infection among vulnerable MSM. From a public health standpoint, interventions that focus on sex-drug reduction strategies in non-treatment settings would appear to sidestep what has otherwise been an impenetrable conundrum of competing hypotheses. Non-injection substance use that commonly accompanies unprotected anal sex with multiple partners remains a potent predictor of HIV seroconversion among MSM and may be increasing in importance as more potent drugs, such as methamphetamine and EDDs, become more popular in high risk sexual settings. The time seems long past to design and evaluate interventions that will disentangle the conjoined epidemics of substance use and high risk sex in this population.