Persistent minority K103N mutations among women exposed to single-dose nevirapine and virologic response to nonnucleoside reverse-transcriptase inhibitor-based therapy.
OBJECTIVE
We investigated whether there are long-lasting effects of exposure to single-dose nevirapine (sdNVP) treatment on virologic response to nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy among human immunodeficiency virus (HIV)-infected women.


METHODS
An observational epidemiologic study was conducted in Johannesburg, South Africa. Initial and sustained virologic response to NNRTI-based therapy was compared between 94 HIV-infected women who had received sdNVP 18-36 months earlier and 60 unexposed, HIV-infected women who had been pregnant 12-36 months earlier. Viral load was measured every 4 weeks up to week 24 and then every 12 weeks up to week 78. Time to viral suppression (viral load, <50 copies/mL) and confirmed rebound in the viral load (viral load, >400 copies/mL) were compared. Drug resistance was assessed using K103N allele-specific real-time polymerase chain reaction assay and population sequencing.


RESULTS
Almost all women (97.5% of sdNVP-exposed women and 91.3% of sdNVP-unexposed women; P = .21) achieved viral suppression by week 24, and similar percentages of sdNVP-exposed and -unexposed women (19.4% and 15.1%, respectively) experienced viral rebound within 78 weeks after treatment (P = .57). K103N was detected with the K103N allele-specific real-time polymerase chain reaction assay among sdNVP-exposed and -unexposed women before treatment; detection was strongly predictive of inadequate viral response: 60.9% of women for whom K103N was detected in either viral RNA or DNA did not experience viral suppression or experienced viral rebound, compared with 15.1% of women for whom K103N was not detected (P < .001). After treatment, the M184V mutation occurred less frequently among sdNVP-exposed women than among sdNVP-unexposed women, but the frequency of NNRTI-associated mutations was similar between these groups of women with inadequate virologic response.


CONCLUSIONS
Exposure to sdNVP in the prior 18-36 months was not associated with a reduced likelihood of achieving and sustaining viral suppression while receiving NNRTI-based therapy. However, women with minority K103N mutations before treatment had a reduced durability of virologic suppression.
Coovadia
Ashraf
A
Empilweni Clinic, Coronation Women and Children Hospital, Johannesburg, South Africa.
Hunt
Gillian
G
Abrams
Elaine J
EJ
Sherman
Gayle
G
Meyers
Tammy
T
Barry
Gill
G
Malan
Eloise
E
Marais
Belinda
B
Stehlau
Renate
R
Ledwaba
Johanna
J
Hammer
Scott M
SM
Morris
Lynn
L
Kuhn
Louise
L
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008137:Longitudinal Studies; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D019829:Nevirapine / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA; D013019:South Africa; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D019829:Nevirapine; D054303:HIV Reverse Transcriptase