Antiretroviral Therapies in Women after Single-Dose Nevirapine Exposure

Brigham and Women's Hospital, Boston, MA, USA.
New England Journal of Medicine (Impact Factor: 55.87). 10/2010; 363(16):1499-509. DOI: 10.1056/NEJMoa0906626
Source: PubMed


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 lopin-avir). 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.

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    • "This secondary analysis used data from the ACTG A5208/OCTANE study. The design and primary results of the OCTANE study have been previously published [11]. In brief, study participants were 741 women with screening CD4 count <200 cells/μL who were antiretroviral-naïve except for prior single dose Nevirapine exposure (SD NVP) in a subset of 241 participants. "
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    • "Recent data in HIV-1–infected women have provided support for the continued use of nevirapine as a first-line treatment option in the absence of previous exposure to this drug. The OCTANE A5208 trial showed that nevirapine, administered as initial treatment in HIV-1–infected women without previous exposure to single-dose nevirapine during pregnancy, was noninferior to ritonavir-boosted lopinavir with respect to virological failure and death.22 However, for women who had been exposed to single-dose nevirapine, significantly more of them reached the primary end point (virological failure, emergence of resistance, and mortality) when they were compared with the ritonavir-boosted lopinavir group.22 "
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    • "To explore the effect of PI-based ART on HIV-infected people residing in malaria-endemic regions of sub-Saharan Africa we undertook a retrospective study examining the incidence of malaria in a group of women enrolled in AACTG 5208 [12]. In this analysis, records of clinical diagnoses of malaria were not included as these may lack sensitivity by missing subclinical infection (malaria parasitaemia without malaria symptoms), and specificity, whereby non-specific febrile illnesses commonly attributable to malaria may be caused by other conditions [13]. "
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