Persistence of nevirapine-resistant HIV-1 in women after single-dose nevirapine therapy for prevention of maternal-to-fetal HIV-1 transmission.
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.
Palmer
S
S
HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA. spalmer@ncifcrf.gov
Boltz
V
V
Martinson
N
N
Maldarelli
F
F
Gray
G
G
McIntyre
J
J
Mellors
J
J
Morris
L
L
Coffin
J
J
D000328:Adult; D000483:Alleles; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D004352:Drug Resistance, Microbial; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D019829:Nevirapine / Q000627:therapeutic use*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D019562:Viral Load
D019380:Anti-HIV Agents; D019829:Nevirapine