1. Nonnucleoside Reverse-transcriptase Inhibitor- vs Ritonavir-boosted Protease Inhibitor–based Regimens for Initial Treatment of HIV Infection: A Systematic Review and Metaanalysis of Randomized Trials
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Patricia Echeverría, John Bartlett, Paul E. Sax, Michael Hughes, Britta Tendal, Sharon A. Riddler, Rebekah Puls, Eric S. Daar, Andreas Lundh, Shahin Lockman, Princy Kumar, Katherine Huppler Hullsiek, Tania B. Huedo-Medina, Kathy Petoumenos, Juan Sierra-Madero, José M. Miró, Magnus Gisslén, Jens D Lundgren, Stephanus Komati, Shinichi Oka, Franco Maggiolo, Álvaro H. Borges, Nathan Clumeck, Paul Khabo, Dominique Costagliola, Rodger D. MacArthur, Alberto Matteelli, and Carlo Torti
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0301 basic medicine ,Microbiology (medical) ,Oncology ,medicine.medical_specialty ,Anti-HIV Agents ,antiretroviral therapy ,HIV Infections ,Pharmacology ,law.invention ,protease inhibitor ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Protease inhibitor (pharmacology) ,030212 general & internal medicine ,Ritonavir ,Reverse-transcriptase inhibitor ,business.industry ,HIV ,HIV Protease Inhibitors ,nonnucleoside reverse transcriptase inhibitor ,metaanalysis ,030112 virology ,Confidence interval ,Discontinuation ,Infectious Diseases ,Meta-analysis ,Relative risk ,HIV/AIDS ,Reverse Transcriptase Inhibitors ,Drug Therapy, Combination ,business ,medicine.drug - Abstract
Background Previous studies suggest that nonnucleoside reverse-transcriptase inhibitors (NNRTIs) cause faster virologic suppression, while ritonavir-boosted protease inhibitors (PI/r) recover more CD4 cells. However, individual trials have not been powered to compare clinical outcomes. Methods We searched databases to identify randomized trials that compared NNRTI- vs PI/r-based initial therapy. A metaanalysis calculated risk ratios (RRs) or mean differences (MDs), as appropriate. Primary outcome was death or progression to AIDS. Secondary outcomes were death, progression to AIDS, and treatment discontinuation. We calculated RR of virologic suppression and MD for an increase in CD4 cells at week 48. Results We included 29 trials with 9047 participants. Death or progression to AIDS occurred in 226 participants in the NNRTI arm and in 221 in the PI/r arm (RR, 1.03; 95% confidence interval, .87-1.22; 12 trials; n = 3825), death in 205 participants in the NNRTI arm vs 198 in the PI/r arm (1.04; 0.86-1.25; 22 trials; n = 8311), and progression to AIDS in 140 participants in the NNRTI arm vs 144 in the PI/r arm (1.00; 0.80-1.25; 13 trials; n = 4740). Overall treatment discontinuation (1.12; 0.93-1.35; 24 trials; n = 8249) and from toxicity (1.21; 0.87-1.68; 21 trials; n = 6195) were comparable, but discontinuation due to virologic failure was more common with NNRTI (1.58; 0.91-2.74; 17 trials; n = 5371). At week 48, there was no difference between NNRTI and PI/r in virologic suppression (RR, 1.03; 0.98-1.09) or CD4(+) recovery (MD, -4.7 cells; -14.2 to 4.8). Conclusions We found no difference in clinical and viro-immunologic outcomes between NNRTI- and PI/r-based therapy.
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- 2016
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