Frequent methamphetamine use associated with primary NNRTI resistance in gay men

Frequent methamphetamine use is associated with primary resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in gay men, according to a study conducted in San Francisco and published in the January 11^th edition of AIDS. The investigators speculate that poor adherence to antiretroviral therapy by gay men on “meth binges” may lead to the development of NNRTI-resistant HIV which is then transmitted to other methamphetamine-using gay men who engage in unprotected sex.

Investigators from the University of California wanted to see if methamphetamine use was associated with primary drug resistance in a cohort of 287 gay men recently infected with HIV. Their study was prompted by the case of the “New York patient” who is thought to have become infected with a highly-resistant strain of HIV via unprotected sex under the influence of methamphetamine. In addition, high rates of methamphetamine use have been reported by gay men in the United States, and several American studies have found an association between risky sexual behaviour and methamphetamine use amongst gay men. The investigators therefore believed it was plausible that methamphetamine could be implicated in the transmission of drug-resistant HIV.

All the study participants had been infected with HIV within the previous twelve months. They completed structured interviews to assess their HIV risk behaviour and drug use in the six months before their HIV seroconversion. None of the individuals included in the investigators’ analysis was taking antiretroviral therapy. Genotypic resistance tests were performed to see if the individuals had primary HIV drug resistance.

Over a quarter (83 individuals, 28%) of men reported methamphetamine use in the previous 30 days, and frequent (weekly or more) methamphetamine use was reported by 12% of men.

Resistance to at least one antiretroviral was present in 77 individuals (26%). The investigators found that men who reported frequent methamphetamine use had a higher prevalence of primary drug resistance (34%) than men who used the drug monthly (21%), or who reported never using the drug (25%).

Further statistical analysis was then performed by the investigators, controlling for factors including ethnicity, number of sex partners, and the use of other illicit drugs. Frequent methamphetamine use remained significantly associated with resistance to any antiretroviral drug (p = 0.006). No such relationship was established for infrequent use of the drug.

Next, the investigators conducted a set of analyses to see if the use of methamphetamine was associated with primary resistance to any particular class of antiretroviral drug. Controlling for the same factors as in their first analysis, they found a strong association between frequent use of the narcotic and resistance to NNRTIs (p = 0.03). No association was found between infrequent use of methamphetamine use and NNRTI resistance, or between frequent and infrequent use of the drug and resistance to protease inhibitors or nucleoside reverse transcriptase inhibitors.

“Our results…suggest that methamphetamine may be an important co-factor in the transmission of NNRTI resistance in this population.”

The authors note that an earlier study found users of methamphetamine disrupted their adherence to antiretroviral therapy during “meth binge episodes” lasting 24-72 hours. They speculate “repeated cycles of such behaviour could result in the emergence of drug resistance because of spasmodic treatment interruptions.” They add, “the convergence of treatment interruptions and high-risk behaviour could be responsible for the high rates of resistance we report here.”