Background:  Non-nucleoside reverse transcriptase inhibitor (NNRTI) use in ART regimes has steadily increased, as has the prevalence of NNRTI-resistance mutations detected in plasma. The incidence of drug-resistant HIV in female genital secretions has been insufficiently studied, particularly from patients with extensive ART exposure. We aim to further characterize the prevalence and persistence of drug resistance in plasma and genital tract from women failing ART regimens, which have included NNRTI.

Methods:  Viral loads from blood and genital samples were determined using the Nuclisens assay. RT and protease sequences could be amplified from both plasma and genital samples from 8 of 20 subjects. These patients had been treated with at least 5 RT inhibitors, including least 1 NNRTI. The average duration of ART was 7.0 years, the average duration of NNRTI therapy was 1.6 years. Of the 8 subjects, 5 were not on NNRTI at the time of analysis. These patients had not taken NNRTI on average of 1.4 years prior to this study. Serial sampling of plasma and genital tract after stopping NNRTI treatment was performed on 4 subjects.

Results:  The 3TC-resistance mutation M184V and NNRTI-resistance mutations at codon K103 were frequently detected in both plasma and genital samples. Of the 8 subjects, 7 had NNRTI mutations detected in both plasma and genital secretions. K103 codon mutations were isolated readily from plasma and the female genital tract, including 4 of 5 patients not currently on NNRTI. These 4 patients had stopped NNRTI for an average of 1.1 years prior to analysis (range 7 months to 2.8 years). Virus from most plasma and the genital samples had similar patterns of protease inhibitor (PI) and RT resistance; however, discordance was found in at least 1 codon in 5 of these 8 patients.

Conclusions:  Multiply resistant HIV is prevalent in genital secretions of women with extensive ART histories. Recent reports suggest that the K103N NNRTI resistance mutation is one of the most common HIV drug-resistance mutations found in plasma during primary infection, and that this virus can persist for years in the absence of drug selection. Our results suggest that NNRTI mutations also are stable in the female genital tract in the absence of drug selection. These findings highlight the potential for further increases in the vertical and sexual transmission of multiply resistant HIV, including those containing NNRTI drug-resistance mutations.

Keywords: Genital; NNRTI; Drug resistance