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

• Published in: The Journal of infectious diseases Vol. 209; no. 5; pp. 703 - 710
• Main Authors: Boltz, Valerie F., Bao, Yajing, Halvas, Elias K., Kearney, Mary F., McIntyre, James A., Schooley, Robert T., Hughes, Michael D., Coffin, John M., Mellors, John W.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2014
• Subjects: Anti-HIV Agents - therapeutic use; Antiretroviral Therapy, Highly Active - methods; Antiretrovirals; Biological and medical sciences; Carts; Clinical trials; Drug resistance; Drug Resistance, Viral - genetics; Female; Fundamental and applied biological sciences. Psychology; Genetic mutation; Genotype; HIV 1; HIV Infections - drug therapy; HIV Infections - genetics; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; HIV/AIDS; Human immunodeficiency virus 1; Humans; Infectious diseases; Major and Brief Reports; Medical sciences; Microbiology; Miscellaneous; Mutation - genetics; Nevirapine - therapeutic use; Polymerase chain reaction; Population size; Treatment Failure; Virology; Women; Human; Antiretroviral agent; RNA-directed DNA polymerase; Nevirapine; HIV-1 virus; Enzyme; Non nucleoside compound; Transferases; Enzyme inhibitor; Retroviridae; Lentivirus; Virus; Infection; Resistance; Nucleotidyltransferases; Treatment; Reverse transcriptase inhibitor; Antiviral; Female; Human immunodeficiency virus; Woman; Failure; antiretroviral therapy failure; single-dose nevirapine; minor drug-resistant variants
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jit635

Background. Low-frequency nevirapine (NVP)-resistant variants have been associated with virologie 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 alíele-specific polymerase chain reaction to quantify NVPresistant 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.