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.
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.


BACKGROUND
NCT00089505.
HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland.
Valerie F
VF
Boltz
Yajing
Y
Bao
Shahin
S
Lockman
Elias K
EK
Halvas
Mary F
MF
Kearney
James A
JA
McIntyre
Robert T
RT
Schooley
Michael D
MD
Hughes
John M
JM
Coffin
John W
JW
Mellors
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D019829:Nevirapine / Q000627:therapeutic use*; D017211:Treatment Failure
D019380:Anti-HIV Agents; D019829:Nevirapine
antiretroviral therapy failure; minor drug-resistant variants; single-dose nevirapine