title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  We found no difference in clinical and viro-immunologic outcomes between NNRTI- and PI/r-based therapy.
authors.affiliation: Centre for Health & Infectious Diseases Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen.
authors.forename: Álvaro H
authors.initials: ÁH
authors.lastname: Borges
authors.affiliation: Department of Internal Medicine, Zealand University Hospital, Roskilde The Nordic Cochrane Centre, Rigshospitalet.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lundh
authors.affiliation: Danish Health Authority, Copenhagen, Denmark.
authors.forename: Britta
authors.initials: B
authors.lastname: Tendal
authors.affiliation: Kilimanjaro Christian Medical Centre, Moshi, Tanzania Duke Global Health Institute, Duke University, Durham, North Carolina.
authors.forename: John A
authors.initials: JA
authors.lastname: Bartlett
authors.affiliation: Department of Infectious Diseases, St Pierre University Hospital, Brussels, Belgium.
authors.forename: Nathan
authors.initials: N
authors.lastname: Clumeck
authors.affiliation: Institut Pierre Louis d'Epidémiologie et de Santé Publique, INSERM et Sorbonne Universités, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.affiliation: Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.affiliation: Department of HIV, Lluita contra la Sida Foundation, Germans Trias i Pujol University Hospital, Autonomous University of Barcelona, Spain.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Echeverría
authors.affiliation: Department of Infectious Diseases, Sahlgrenska Academy at the University of Gothenburg, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Gisslén
authors.affiliation: Department of Allied Health Sciences, University of Connecticut, Hartford.
authors.forename: Tania B
authors.initials: TB
authors.lastname: Huedo-Medina
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hughes
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis.
authors.forename: Katherine
authors.initials: K
authors.lastname: Huppler Hullsiek
authors.affiliation: Project Phidisa, Pretoria, South Africa.
authors.forename: Paul
authors.initials: P
authors.lastname: Khabo
authors.affiliation: Project Phidisa, Pretoria, South Africa.
authors.forename: Stephanus
authors.initials: S
authors.lastname: Komati
authors.affiliation: Georgetown University Hospital, Washington D.C.
authors.forename: Princy
authors.initials: P
authors.lastname: Kumar
authors.affiliation: 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.
authors.forename: Shahin
authors.initials: S
authors.lastname: Lockman
authors.affiliation: Newland Immunology Center of Excellence, Southfield, Michigan.
authors.forename: Rodger D
authors.initials: RD
authors.lastname: MacArthur
authors.affiliation: Divisione di Malattie Infettive, Ospedali Riuniti, Bergamo.
authors.forename: Franco
authors.initials: F
authors.lastname: Maggiolo
authors.affiliation: Institute of Infectious and Tropical Diseases, University of Brescia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Matteelli
authors.affiliation: Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Miro
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.affiliation: Kirby institute, UNSW Australia, Sydney, New South Wales.
authors.forename: Kathy
authors.initials: K
authors.lastname: Petoumenos
authors.affiliation: Kirby institute, UNSW Australia, Sydney, New South Wales.
authors.forename: Rebekah L
authors.initials: RL
authors.lastname: Puls
authors.affiliation: Department of Medicine, University of Pittsburgh, Pennsylvania.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Riddler
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico.
authors.forename: Juan
authors.initials: J
authors.lastname: Sierra-Madero
authors.affiliation: University Unit of Infectious Diseases, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.affiliation: Centre for Health & Infectious Diseases Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen.
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019438:Ritonavir
keywords: HIV; antiretroviral therapy; metaanalysis; nonnucleoside reverse transcriptase inhibitor; protease inhibitor