Low-frequency nevirapine (NVP)-resistant HIV-1 variants are not associated with failure of antiretroviral therapy in women without prior exposure to single-dose NVP.

TitleLow-frequency nevirapine (NVP)-resistant HIV-1 variants are not associated with failure of antiretroviral therapy in women without prior exposure to single-dose NVP.
Publication TypeJournal Article
Year of Publication2014
AuthorsBoltz VF, Bao Y, Lockman S, Halvas EK, Kearney MF, McIntyre JA, Schooley RT, Hughes MD, Coffin JM, Mellors JW
Corporate AuthorsOCTANE/A5208 Team
JournalJ Infect Dis
Volume209
Issue5
Pagination703-10
Date Published2014 Mar 1
ISSN1537-6613
KeywordsAnti-HIV Agents, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, Female, Genotype, HIV Infections, HIV-1, Humans, Mutation, Nevirapine, Treatment Failure
Abstract

BACKGROUND: Low-frequency nevirapine (NVP)-resistant variants have been associated with virologic failure (VF) of initial NVP-based combination antiretroviral therapy (cART) in women with prior exposure to single-dose NVP (sdNVP). We investigated whether a similar association exists in women without prior sdNVP exposure.

METHODS: Pre-cART plasma was analyzed by allele-specific polymerase chain reaction to quantify NVP-resistant mutants in human immunodeficiency virus-infected African women without prior sdNVP who were starting first-line NVP-based cART in the OCTANE/A5208 trial 2. Associations between NVP-resistant mutants and VF or death were determined and compared with published results from women participating in the OCTANE/A5208 trial 1 who had taken sdNVP and initiated NVP-based cART.

RESULTS: Pre-cART NVP-resistant variants were detected in 18% (39/219) of women without prior sdNVP exposure, compared to 45% (51/114) with prior sdNVP exposure (P < .001). Among women without prior sdNVP exposure, 8 of 39 (21%) with NVP-resistant variants experienced VF or death vs 31 of 180 (17%) without such variants (P = .65); this compares with 21 of 51 (41%) vs 9 of 63 (14%) among women with prior exposure (P = .001).

CONCLUSIONS: The risk of VF on NVP-based cART from NVP-resistant variants differs between sdNVP-exposed and -unexposed women. This difference may be driven by drug-resistance mutations emerging after sdNVP exposure that are linked on the same viral genome.

CLINICAL TRIALS REGISTRATION: NCT00089505.

DOI10.1093/infdis/jit635
Alternate JournalJ. Infect. Dis.
PubMed ID24443547
PubMed Central IDPMC3923545
Grant List1 U01-AI068634 / AI / NIAID NIH HHS / United States
1 U01AI068636-01 / AI / NIAID NIH HHS / United States
1U01 AI069494-01 / AI / NIAID NIH HHS / United States
P30 AI027763 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069456 / AI / NIAID NIH HHS / United States
UM1 AI069463 / AI / NIAID NIH HHS / United States
UM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States