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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    ABSTRACT: Background A subset of HIV-1 infected patients starting highly active antiretroviral treatment (HAART) experience suboptimal CD4 response (SCR) despite virologic suppression. We studied the rate of and risk factors for SCR among women starting HAART in the ACTG A5208 study conducted in 7 African countries. 741 HAART-naive women with screening CD4 count <200 cells/μL were randomized to start HAART with Tenofovir/Emtricitabine plus either Nevirapine or Lopinavir/Ritonavir. Methods This analysis includes the 625 women who remained on-study through 48 weeks without experiencing protocol-defined virologic failure. We defined SCR as < 100 CD4 cells/μL increase from baseline and absolute CD4 cell count < 350 cells/μL, both at 48 weeks after HAART initiation. Results The baseline characteristics for the 625 women prior to HAART initiation were: median age 33 years, screening CD4 count 134 cells/μL, and HIV-1 RNA 5.1 log10 copies/mL; 184 (29%) were WHO Stage 3 or 4. Seventy one (11%) of these 625 women experienced SCR. Baseline factors independently associated with increased odds of SCR included older age, lower HIV-1 RNA, positive Hepatitis B surface antigen, and site location. At 96 weeks, only 6% of the SCR group had CD4 ≥ 350 cells/μL compared with 67% in the non SCR group. Conclusion After starting HAART, 11% of women with virologic suppression through 48 weeks experienced SCR. These patients were also less likely to achieve CD4 ≥ 350 cells/μL by 96 weeks. The underlying causes and long term clinical implications of SCR deserve further investigation. Trial registration Identifier: NCT00089505
    BMC Infectious Diseases 06/2014; 14(1):331. DOI:10.1186/1471-2334-14-331 · 2.61 Impact Factor
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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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    ABSTRACT: We reviewed the current information available on nevirapine immediate- and extended-release formulations and its role in single-dose and combination antiretroviral therapy. Nevirapine was approved in 1996 and was the first non-nucleoside reverse-transcriptase inhibitor available for the treatment of HIV-1 infection. Nevirapine has demonstrated good efficacy and a well-characterized safety profile. A major drawback is the low genetic barrier, allowing the emergence of resistance in the presence of single mutations in the reverse-transcriptase gene. This shortcoming is particularly relevant when nevirapine is administered in a single dose to prevent mother-to-child transmission of HIV-1 infection, compromising the efficacy of future non-nucleoside reverse transcriptase-inhibitor regimens. Studies published recently have probed the noninferiority of nevirapine compared to ritonavir-boosted atazanavir with both tenofovir disoproxil fumarate and emtricitabine in antiretroviral treatment-naïve patients. In 2011, a new formulation of nevirapine (nevirapine extended release) that allowed once-daily dosing was approved by the Food and Drug Administration and by the European Medicines Agency. VERxVe, a study comparing nevirapine extended release with nevirapine immediate release in antiretroviral treatment-naïve patients, and TRANxITION, a study carried out in antiretroviral treatment-experienced patients who switched therapy from nevirapine immediate release to nevirapine extended release, provided data on the noninferiority of the new formulation of nevirapine compared with nevirapine immediate release in terms of efficacy and safety. Nevirapine extended release will further increase the durability and persistence of nevirapine-containing antiretroviral therapy, allowing once-daily dosing regimens.
    HIV/AIDS - Research and Palliative Care 11/2012; 4:169-79. DOI:10.2147/HIV.S35564
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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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    ABSTRACT: HIV protease inhibitors (PIs) show antimalarial activity in vitro and in animals. Whether this translates into a clinical benefit in HIV-infected patients residing in malaria-endemic regions is unknown. We studied the incidence of malaria, as defined by blood smear positivity or a positive Plasmodium falciparum histidine-rich protein 2 antigen test, among 444 HIV-infected women initiating antiretroviral treatment (ART) in the OCTANE trial (A5208; NCT00089505). Participants were randomized to treatment with PI-containing vs. PI-sparing ART, and were followed prospectively for ≥48 weeks; 73% also received cotrimoxazole prophylaxis. PI-containing treatment was not associated with protection against malaria in this study population.
    PLoS ONE 04/2012; 7(4):e34399. DOI:10.1371/journal.pone.0034399 · 3.23 Impact Factor
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