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
Valerie F Boltz, Yajing Bao, Shahin Lockman, Elias K Halvas, Mary F Kearney, James A McIntyre, Robert T Schooley, Michael D Hughes, John M Coffin, John W Mellors, OCTANE/A5208 Team, Beth Zwickl, Cissykityo Mutuluuza, Christine Kaseba, Charles C Maponga, Heather Watts, Daniel Kuritzkes, Thomas B Campbell, Lynn Kidd-Freeman, Monica Carten, Jane Hitti, Mary Marovich, Peter N Mugyenyi, Sandra Rwambuya, Ian M Sanne, Beverly Putnam, Cheryl Marcus, Carolyn Wester, Robin Difrancesco, Elias Halvas, Annie Beddison, Sandra Lehrman, Francesca Aweeka, Betty Dong, Peter Ndhleni Ziba, Michael S Saag, William C Holmes, Scott M Hammer, Valerie F Boltz, Yajing Bao, Shahin Lockman, Elias K Halvas, Mary F Kearney, James A McIntyre, Robert T Schooley, Michael D Hughes, John M Coffin, John W Mellors, OCTANE/A5208 Team, Beth Zwickl, Cissykityo Mutuluuza, Christine Kaseba, Charles C Maponga, Heather Watts, Daniel Kuritzkes, Thomas B Campbell, Lynn Kidd-Freeman, Monica Carten, Jane Hitti, Mary Marovich, Peter N Mugyenyi, Sandra Rwambuya, Ian M Sanne, Beverly Putnam, Cheryl Marcus, Carolyn Wester, Robin Difrancesco, Elias Halvas, Annie Beddison, Sandra Lehrman, Francesca Aweeka, Betty Dong, Peter Ndhleni Ziba, Michael S Saag, William C Holmes, Scott M Hammer
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.
Keywords: antiretroviral therapy failure; minor drug-resistant variants; single-dose nevirapine.
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Source: PubMed