New study results have established methamphetamine use as an independent risk factor for HIV transmission and, when combined with other risk factors like unprotected receptive anal intercourse with multiple partners, the chances of seroconversion increases substantially. The new analysis, reported by researchers associated with the U.S.-based Multicenter AIDS Cohort Study (MACS), is to be published in a forthcoming issue of the Journal of Acquired Immune Deficiency Syndromes.

Methamphetamine is a powerful central nervous system stimulant that has been popular among men who have sex with men (MSM) for many years, notably due to its ability to prolong wakefulness, reduce inhibitions, and heighten sexual desire. 

Several behavioral studies have demonstrated that MSM who use methamphetamine are more likely to engage in high-risk sexual practices, putting them at an increased risk for HIV and other sexually transmitted infections (STIs).

A notable criticism of many such studies is that they only demonstrate a high prevalence of HIV among methamphetamine users. In other words, while there may be high rates of HIV infection among MSM who have reported using methamphetamine – that is, a correlation between meth use and HIV infection among gay and bisexual men – these data do not support the hypothesis that there is causation (a causative role) between methamphetamine and HIV infection. 

There have been a few studies examining the incidence of new HIV infections among meth users, compared to MSM who have never used the drug.  Epidemiological data such as these are needed to establish causation. However, results from incidence studies have been limited, due to the small number of seroconversions documented and the self-reported data collected over short follow-up periods. These studies were also hobbled by inadequate data adjustments for additional HIV risk factors (e.g., other recreational drugs used and risky sexual activities with different partners) and limited geographic diversity (e.g., one U.S. city only). 

To take a closer look at the causative link between methamphetamine and HIV seroconversion, researchers  – under the direction of Michael Plankey, PhD, of Georgetown University Medical Center in Washington, DC  – turned to data collected in the MACS. 

According to David Ostrow, MD, PhD, of the Chicago MACS Center and a member of Dr. Plankey's study team, "the strength of the MACS is that it is a relatively stable population of gay and bisexual men that has been followed prospectively since 1984, at the very beginning of the scientific study of the natural history of AIDS, with additional men recruited in 1987 to 1988 and 2000 to 2001. Given the semi-annual visits at which both behavioral and medical, as well as HIV testing and assessment is performed, we can look at causal relationships between sexual or drug behaviors and seroconversion, even though the exact nature of that causality is not necessarily elucidated in the study." 

A total of 6,973 HIV-negative and HIV-positive MSM have been recruited into the MACS, at four major research centers in Baltimore, Chicago, Los Angeles, and Pittsburgh, over the past 23 years. Among all volunteers enrolled in the MACS, between 23% and 28% of the men – depending on the research site – seroconverted at some point during the study, whereas 23% to 28% remained HIV negative. A total of 4,003 MSM who were HIV negative upon entering the study were included in the methamphetamine analysis.

Men who seroconverted were similar to the men who remained HIV negative in terms of age at study entry, race/ethnicity, and educational levels. Compared to those who remained HIV negative, those who seroconverted were more likely to have ever used methamphetamine, poppers, cocaine, or ecstasy at any time while participating in the MACS.  Approximately 94% of those who seroconverted while in the MACS reported having had unprotected receptive anal sex at least once while in the study. 

MSM who used methamphetamine faced a 46% greater risk – expressed by the researcher as a fold increase, or "relative hazard rate," of 1.46 – of becoming infected with HIV, compared to MSM who did not report using the drug. 

In light of the high prevalence of popper use (93% of meth users also reported using inhalable nitrates), the MACS researchers also reported data involving the relationship between both drugs combined and HIV seroconversion. Accordingly, there was a threefold increase in the risk of acquiring HIV among those with a history of methamphetamine and popper use, compared to those not using either drug.

In Dr. Ostrow's own words, the relationship between methamphetamine/poppers use among MSM and HIV infection is "relatively modest." However, as explained by Spencer Cox, Founder and Executive Director of the gay health-focused Medius Institute in New York, "these data are by no means insignificant. The risk increase documented in this study is similar to increases found in other studies."

Dr. Ostrow explains that these data are important, in that they establish a causal relationship between methamphetamine and/or popper use and HIV risk, "but does not tell us how A leads to B. This could be because meth users are having unprotected anal sex with other men who are more likely to be HIV positive, or are more likely to forgo condoms when they use meth, or that meth use leads to marathon anal sex sessions that involve more trauma to the anal mucosa and, thus, easier passage of HIV from the ‘top' to the ‘bottom'."

He also points out that relative hazard rates in the 1.5 to 2.0 range, as observed in this study, do not suggest a very strong or effective mechanism of enhancement of HIV transmission in the presence of either methamphetamine or poppers. However, when risk factors are combined, the risk of HIV infection increases dramatically.  For example, among meth users reporting unprotected receptive anal sex with one partner, the risk of infection almost tripled (a 2.71-fold increase).  Meth users engaging in unprotected receptive anal sex with five or more partners were nearly 14 times (a 13.57-fold increase) as likely to become infected. 

Additional data, reported by Dr. Ostrow and his colleagues at the XVI International AIDS Conference last summer in Toronto, demonstrated that, among men combining stimulants with poppers and erectile dysfunction drugs like Viagra® (sildenafil), "we see a much greater [risk] of seroconversion, suggesting that in those circumstances, there is a multiplicative effect involving multiple mechanisms involved."

Dr. Ostrow stresses that, from a public health standpoint, it is time to move beyond criticism of studies that don't fully elucidate the causal relationship between methamphetamine use and HIV risk. "It is dangerous to rely on the lack of a ‘smoking gun' in terms of the exact mechanism to deny the need to recognize and change ones behavior to avoid HIV infection or transmission. This is analogous to the public outcry when I and others suggested in 1982 that gay men refrain from unprotected anal intercourse until we knew what was causing AIDS, as we definitely knew that unprotected anal sex was the leading route of infection or exposure to whatever the causal factor would turn out to be. 

"I feel the same about educating gay men now, to the dangers involved in barebacking, especially when stimulants, poppers, and erectile dysfunction drugs are involved, even though we don't know the exact mechanism for these findings, that the risk of infection is at least tenfold higher than with either stimulants or poppers alone." 

Mr. Cox agrees. "The research linking methamphetamine use, unsafe sex, and HIV transmission is pretty clear," he says. "Its time to stop focusing on the bits and pieces and take a step back and look at the larger picture of why gay men use drugs that place them at significant risk."