Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1 transmission

Abstract

Single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission of HIV-1 can select nevirapine (NVP)-resistant variants, but the frequency, duration, and clinical significance of this resistance is not well defined. We used a sensitive allele-specific PCR assay to assess the emergence and persistence of NVP-resistant variants in plasma samples from 22 women with HIV-1 subtype C infection who participated in a study of sdNVP for prevention of mother-to-child transmission of HIV-1. The women were categorized into three groups on the basis of detection of NVP resistance by standard genotype analysis. Group 1 (n = 6) had NVP resistance detected at 2 and 6 mo after sdNVP, but not at 12 mo. Group 2 (n = 9) had NVP resistance detected at 2 mo, but not 6 mo. Group 3 (n = 7) had no NVP resistance detected at any time point. Allele-specific PCR analysis for the two most common NVP resistance mutations (K103N and Y181C) detected NVP-resistant variants in most (16 of 21) samples that were negative for NVP resistance by standard genotype, at levels ranging from 0.1% to 20% 1 yr after treatment. The frequency of NVP-resistant mutations decreased over time, but persisted above predose levels for more than 1 yr in > or = 23% of the women. These findings highlight the urgent need for studies assessing the impact of sdNVP on the efficacy of subsequent antiretroviral therapy containing NVP or other nonnucleoside reverse transcriptase inhibitors.

Fig. 1.

Percentage of patients with NNRTI-resistant variants 103N and/or 181C. The percentage of patients with 103N and/or 181C mutations detected by standard genotyping (gray lines and squares) was compared with the percentage of patients with mutations detected by allele-specific PCR (dashed lines and circles). Samples were divided into three groups on the basis of standard genotype results: group 1, positive for a NNRTI-resistant mutation at 2 and 6 mo (A); group 2, positive at 2 mo only (B); and group 3, never positive (C).

Fig. 2.

Average percent of NNRTI-resistant variants 103N (AAC and AAT) (A and B, respectively) and 181C (C) for each patient group. Longitudinal plasma samples were obtained from patients before and after sdNVP therapy, and the percentage of each mutant population was measured by allele-specific PCR. The average percentage for each group was then calculated. Solid lines with circles represent group 1, dashed lines with squares represent group 2, and dark-gray short dashes with triangles indicate group 3. The background level for each assay is shown.