Antiretroviral therapies in women after single-dose nevirapine exposure.

TitleAntiretroviral therapies in women after single-dose nevirapine exposure.
Publication TypeJournal Article
Year of Publication2010
AuthorsLockman S, Hughes MD, McIntyre J, Zheng Y, Chipato T, Conradie F, Sawe F, Asmelash A, Hosseinipour MC, Mohapi L, Stringer E, Mngqibisa R, Siika A, Atwine D, Hakim J, Shaffer D, Kanyama C, Wools-Kaloustian K, Salata RA, Hogg E, Alston-Smith B, Walawander A, Purcelle-Smith E, Eshleman S, Rooney J, Rahim S, Mellors JW, Schooley RT, Currier JS
Corporate AuthorsOCTANE A5208 Study Team
JournalN Engl J Med
Volume363
Issue16
Pagination1499-509
Date Published2010 Oct 14
ISSN1533-4406
KeywordsAdenine, Adult, Anti-HIV Agents, Anti-Retroviral Agents, CD4 Lymphocyte Count, Deoxycytidine, Drug Therapy, Combination, Emtricitabine, Female, Follow-Up Studies, HIV Infections, HIV-1, Humans, Infectious Disease Transmission, Vertical, Kaplan-Meier Estimate, Linear Models, Lopinavir, Nevirapine, Organophosphonates, Pregnancy, Pregnancy Complications, Infectious, Pyrimidinones, Ritonavir, Statistics, Nonparametric, Tenofovir, Treatment Failure, Young Adult
Abstract

BACKGROUND: Peripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus.

METHODS: In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death.

RESULTS: A total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P=0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single-dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died.

CONCLUSIONS: In women with prior exposure to peripartum single-dose nevirapine (but not in those without prior exposure), ritonavir-boosted lopinavir plus tenofovir–emtricitabine was superior to nevirapine plus tenofovir–emtricitabine for initial antiretroviral therapy. (Funded by the National Institute of Allergy and Infectious Diseases and the National Research Center; ClinicalTrials.gov number, NCT00089505.).

DOI10.1056/NEJMoa0906626
Alternate JournalN. Engl. J. Med.
PubMed ID20942666
PubMed Central IDPMC2994321
Grant List5401A1068636-04 / / PHS HHS / United States
AI38838 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
K24 AI056933 / AI / NIAID NIH HHS / United States
K24 AI056933-08 / AI / NIAID NIH HHS / United States
K24 AI56933 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068634-06 / AI / NIAID NIH HHS / United States
U01 AI068636-06 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States