Special Coverage: 12th Conference on Retroviruses and Opportunistic Infections

Drug resistant HIV lingers in female genital tract

Transmission of resistance feared

Researchers have learned that multiple-resistant HIV is prevalent in genital tracts of women with long antiretroviral therapy histories, and resistant virus can persist even years after the therapy associated with the resistance has stopped.1

Investigators studied resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in blood and genital samples from eight HIV-infected women who had been on antiretroviral therapy for an average of seven years.1

"It was surprising that we could detect the resistance mutation even in patients off NNRTI drugs for years," says Michael Newstein, MD, an assistant professor of medicine and research at the Brown University School of Medicine in Providence, RI.

"We had patients who were up to 42 months off therapy, but we could isolate NNRTI mutations, both in their plasma and genital tracts," he says. "We studied other resistance, but in our small study, it seemed the NNRTIs were more readily isolated than other mutations."

Also, investigators focused on NNRTIs because of the very important role the drugs have in most new antiretroviral treatment regimens, Newstein notes.

"They have a particularly important role for women because they’re included in many treatments to prevent mother to child transmission, and that was another reason we wanted to look at mutations in the female genital tract," he says. "Most of the mutations confer cross-resistance, and the one we focused on in particular was the K103n."

Researchers developed a technique to isolate even low frequencies of K103n, which typically in genotype assays can be detected when resistance is present in 5% to 20% of circulating virus, Newstein adds.

"We could detect it at much lower levels of resistance with our assays," he says.

This study follows on the heels of recent and widely publicized research findings that even one dose of nevirapine could select for resistance, chiefly to K103n, and that this mutation can persist in the plasma for many months, Newstein says.

"What we’re showing is in a different group of patients who received nevirapine or efavirenz, we could show that these patients — even though they were off the therapy for many months or years — still had the same mutation detectable in the plasma and in the genital tract," he says.

The study did not address adherence, although the patients included in the study were failing antiretroviral therapy, and they typically had a backgrounds of drug abuse, indicating potential poor adherence, Newstein says.

"One of the things we wanted to find out is how long these [resistant] viruses can persist and whether there will be a difference when we are looking at later time points if there’s been a discontinuation of NNRTI agents," he says. "How long can we detect these viruses in the genital tract and blood, and are there times when they’re not detectable because that would be significant as far as potential transmission issues?"

The study concludes that there is potential for further increases in the vertical and sexual transmission of multiple-drug resistant HIV, including NNRTI drug resistant mutations.1

Reference

  1. Newstein M, Martin T, Losikoff P, et al. Prevalence and persistence of NNRTI mutations in the female genital tract. Abstract presented at the 12th Conference on Retroviruses and Opportunistic Infections, Boston; February 2005. Abstract 671.