Antiretroviral therapies in women after single-dose nevirapine exposure.
| Title: | Antiretroviral therapies in women after single-dose nevirapine exposure. |
|---|---|
| Authors: | Lockman S; Brigham and Women's Hospital, Boston, MA, USA. slockman@hsph.harvard.edu; 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 Authors: | OCTANE A5208 Study Team |
| Source: | The New England journal of medicine [N Engl J Med] 2010 Oct 14; Vol. 363 (16), pp. 1499-509. |
| Publication Type: | Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural |
| Language: | English |
| Journal Info: | Publisher: Massachusetts Medical Society Country of Publication: United States NLM ID: 0255562 Publication Model: Print Cited Medium: Internet ISSN: 1533-4406 (Electronic) Linking ISSN: 00284793 NLM ISO Abbreviation: N Engl J Med Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Boston, Massachusetts Medical Society. |
| MeSH Terms: | HIV-1*; Anti-Retroviral Agents/*therapeutic use ; HIV Infections/*drug therapy ; Nevirapine/*administration & dosage ; Pregnancy Complications, Infectious/*drug therapy; Adenine/analogs & derivatives ; Adenine/therapeutic use ; Anti-HIV Agents/administration & dosage ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/therapeutic use ; HIV Infections/mortality ; HIV Infections/transmission ; Infectious Disease Transmission, Vertical/prevention & control ; Organophosphonates/therapeutic use ; Pyrimidinones/therapeutic use ; Ritonavir/therapeutic use ; Adult ; CD4 Lymphocyte Count ; Drug Therapy, Combination ; Emtricitabine ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Linear Models ; Lopinavir ; Pregnancy ; 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.). |
| Comments: | Comment in: N Engl J Med. 2010 Oct 14;363(16):1570-2. doi: 10.1056/NEJMe1009863.. (PMID: 20942674) |
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| Grant Information: | AI68634 United States AI NIAID NIH HHS; K24 AI056933 United States AI NIAID NIH HHS; UM1 AI068634 United States AI NIAID NIH HHS; K24 AI56933 United States AI NIAID NIH HHS; U01 AI068636 United States AI NIAID NIH HHS; AI38838 United States AI NIAID NIH HHS; 5401A1068636-04 United States PHS HHS; U01AI068636 United States AI NIAID NIH HHS; U01 AI068634 United States AI NIAID NIH HHS; UM1 AI068636 United States AI NIAID NIH HHS |
| Contributed Indexing: | Investigator: B Zwickl; CK Mutuluuza; C Kaseba; CC Maponga; H Watts; D Kuritzkes; TB Campbell; L Kidd-Freeman; M Carten; J Hitti; M Marovich; PN Mugyenyi; S Rwambuya; IM Sanne; B Putnam; C Marcus; C Wester; R DiFrancesco; E Halvas; A Beddison; S Lehrman; F Aweeka; B Dong; PN Ziba; MS Saag; WC Holmes; SM Hammer; E Dangaiso; MS Rassool; J Tsotsotetsi; C Potani; R Mwausegha; F Laher; R Hen-Boisen; K Kirwa; A Nzioka; M Chibowa; J Stringer; K Sebina; K Mburu; T Kakhu; B Moorad; C Kityo; S Rwambuya; F Amod; U Lalloo; S Pillay; X Sun; A Nair; LM Smith; J Tutko; C Lee; L Purdue; E Ferguson; A Martinez; Y Delph; N Gettinger; L Berman; L Boone; B Adedeji |
| Molecular Sequence: | ClinicalTrials.gov NCT00089505 |
| Substance Nomenclature: | 0 (Anti-HIV Agents); 0 (Anti-Retroviral Agents); 0 (Organophosphonates); 0 (Pyrimidinones); 0W860991D6 (Deoxycytidine); 2494G1JF75 (Lopinavir); 99DK7FVK1H (Nevirapine); 99YXE507IL (Tenofovir); G70B4ETF4S (Emtricitabine); JAC85A2161 (Adenine); O3J8G9O825 (Ritonavir) |
| Entry Date(s): | Date Created: 20101015 Date Completed: 20101021 Latest Revision: 20250529 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC2994321 |
| DOI: | 10.1056/NEJMoa0906626 |
| PMID: | 20942666 |
| Database: | MEDLINE |
Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural