Álvaro H Borges1, Andreas Lundh2, Britta Tendal3, John A Bartlett4, Nathan Clumeck5, Dominique Costagliola6, Eric S Daar7, Patrícia Echeverría8, Magnus Gisslén9, Tania B Huedo-Medina10, Michael D Hughes11, Katherine Huppler Hullsiek12, Paul Khabo13, Stephanus Komati13, Princy Kumar14, Shahin Lockman15, Rodger D MacArthur16, Franco Maggiolo17, Alberto Matteelli18, Jose M Miro19, Shinichi Oka20, Kathy Petoumenos21, Rebekah L Puls21, Sharon A Riddler22, Paul E Sax23, Juan Sierra-Madero24, Carlo Torti25, Jens D Lundgren1. 1. Centre for Health & Infectious Diseases Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen. 2. Department of Internal Medicine, Zealand University Hospital, Roskilde The Nordic Cochrane Centre, Rigshospitalet. 3. Danish Health Authority, Copenhagen, Denmark. 4. Kilimanjaro Christian Medical Centre, Moshi, Tanzania Duke Global Health Institute, Duke University, Durham, North Carolina. 5. Department of Infectious Diseases, St Pierre University Hospital, Brussels, Belgium. 6. Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM et Sorbonne Universités, Paris, France. 7. Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California. 8. Department of HIV, Lluita contra la Sida Foundation, Germans Trias i Pujol University Hospital, Autonomous University of Barcelona, Spain. 9. Department of Infectious Diseases, Sahlgrenska Academy at the University of Gothenburg, Sweden. 10. Department of Allied Health Sciences, University of Connecticut, Hartford. 11. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts. 12. Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis. 13. Project Phidisa, Pretoria, South Africa. 14. Georgetown University Hospital, Washington D.C. 15. Department of Immunology and Infectious Diseases, Harvard School of Public Health Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 16. Newland Immunology Center of Excellence, Southfield, Michigan. 17. Divisione di Malattie Infettive, Ospedali Riuniti, Bergamo. 18. Institute of Infectious and Tropical Diseases, University of Brescia, Italy. 19. Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Spain. 20. AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan. 21. Kirby institute, UNSW Australia, Sydney, New South Wales. 22. Department of Medicine, University of Pittsburgh, Pennsylvania. 23. Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 24. Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico. 25. University Unit of Infectious Diseases, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy.
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.
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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