Program Schedule

Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs) Comparing Initial Non-Nucleoside Reverse-Transcriptase Inhibitor (NNRTI)- versus Ritonavir Boosted Protease Inhibitor (PI/r)-based Anti-Retroviral Therapy (ART)

Session: Oral Abstract Session: HIV Antiretroviral Therapy
Thursday, October 9, 2014: 2:00 PM
Room: The Pennsylvania Convention Center: 107-AB

Background: Results from RCTs suggest that NNRTIs may cause faster virological suppression and PI/r may recover more CD4 cells. It is unknown if differences in immunological and virological endpoints are clinically relevant, as individual RCTs have not been powered to compare clinical outcomes.

Methods: We searched established databases to identify RCTs comparing NNRTI- vs PI/r-based initial ART. A meta-analysis using random-effects model calculated risk ratios (RRs) or mean differences (MDs), as appropriate. The primary endpoint was death or progression to AIDS. Secondary endpoints were: death, progression to AIDS and treatment discontinuation. Results were from intention-to-treat analyses. We calculated RR of virological suppression and MD for increase of CD4 cells at week 48, a time point at which these data were available in most RCTs.

Results: We included 27 RCTs with 9515 patients. Of 4848 patients assigned to an NNRTI, 3636 received efavirenz and 1212 nevirapine. Of 4667 patients on PI/r, 2661 received lopinavir, 1498 atazanavir and 508 another PI/r. Death or progression to AIDS occurred in 308 patients in the NNRTI arm and 301 in the PI/r arm (RR: 1.03 [95%CI: 0.89-1.19], 11 RCTs; n=4239), death in 256 patients in the NNRTI arm vs 249 in the PI/r arm (1.03 [0.87-1.21]; 21 RCTs; n=8671) and progression to AIDS in 193 patients in the NNRTI arm vs 184 in the PI/r arm (1.06 [0.87-1.29]; 10 RCTs; n=4809)  Overall treatment discontinuation (1.15 [0.96-1.38], 22 RCTs, n=8703) and from toxicity (1.25 [0.87-1.79], 19 RCTs; n=6685) were similar, but the risk of discontinuation due to RCT-defined virological failure  was higher with NNRTI (1.89 [1.02-3.51], 15 RCTs; n=5830). At week 48, there was no difference between NNRTI- and PI/r-based ART in virological suppression (RR: 1.03 [0.96-1.12], 13 RCTs; n=4010) or increase of CD4 cells (MD: -6.95 cells [-16.32 to 2.42], 13 RCTs; n=4010).

Conclusion: In a comprehensive meta-analysis of RCTs, we found no difference in clinical outcomes between subjects randomized to NNRTI- or PI/r-based initial ART. An individual patient data meta-analysis is warranted to investigate differences in adverse event profiles and the dynamics of immune recovery and virological suppression with individual NNRTI- or PI/r- based ART regimens.


Álvaro H Borges, MD, MSc, Centre for Health & Infectious Diseases Research (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Copenhagen, Denmark, Andreas Lundh, MD, MSc, PhD, Department of Infectious Diseases, Hvidovre Hospital, Copenhagen, Denmark; The Nordic Cochrane Group, Copenhagen, Denmark, Britta Tendal, PhD, Sundhedsstyrelsen, Copenhagen, Denmark, Tania B Huedo-Medina, PhD, Department of Allied Health Sciences, University of Connecticut, Hartford, CT, John a Bartlett, MD, Kilimanjaro Christian Medical Centre, Moshi, Tanzania; Duke Global Health Institute, Duke University, Durham, NC, Dominique Costagliola, PhD, Institut Pierre Louis d’Epidémiologie et de Santé Publique, UMR_S 1136, INSERM et Sorbonne Universités, UPMC Univ Paris 06, Paris, France, Nathan Clumeck, MD, Department of Infectious Diseases, St Pierre University Hospital, Brussels, Belgium, Brussels, Belgium, Eric S Daar, MD, Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, CA, Edwin Dejesus, MD, FACP. FIDSA, Orlando Immunology Center, Orlando, FL, Patricia Echeverría, MD, Department of HIV, Lluita contra la Sida Foundation, Germans Trias i Pujol University Hospital, Barcelona, Spain, Magnus Gisslén, MD, PhD, Department of Infectious Diseases, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden, Miwako Honda, MD, Department of General medicine, National Hospital Organization Tokyo Medical Center, Tokyo, Japan, Michael Hughes, Ph.D., Harvard School of Public Health, Boston, MA, P Khabo, PhD, Project Phidisa, South African Military Health Services, Centurion, South Africa, Stephanus Komati, MD, PhD, Project Phidisa, Pretoria, South Africa, Princy N. Kumar, MD, Georgetown University Medical Center, Washington, DC, Shahin Lockman, MD, MSc, Brigham and Women's Hospital, Boston, MA, Rodger Macarthur, MD, Division of Infectious Diseases, Wayne State University, Detroit, MI, Franco Maggiolo, MD, PhD, Divisione di Malattie Infettive, Ospedali Riuniti, Bergamo, Italy, Alberto Matteelli, MD, Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy, José M Miró, MD, Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain, Rebekah L Puls, MD, PhD, Kirby institute, UNSW Australia, New South Wales, Australia, Sydney, Australia, Sharon Riddler, MD, MPH, University of Pittsburgh, Pittsburgh, PA, Paul Sax, MD, FIDSA, Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, Juan Sierra-Madero, MD, Inst. Nal. Ciencias Médicas y Nutrición SZ, Mexico City, Mexico, Carlo Torti, MD, University Unit of Infectious Diseases, Department of Medical and Surgical Sciences, University, Catanzaro, Italy, Jens Lundgren, MD, D.M.Sc., Professor, Department of Infectious Diseases and Rheumatology, Chip, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark and Global Consortium METART


H. Borges, None

A. Lundh, None

B. Tendal, None

T. B. Huedo-Medina, None

J. A. Bartlett, None

D. Costagliola, None

N. Clumeck, None

E. S. Daar, Abbvie: Consultant, Consulting fee
Bristol Myers Squibb: Consultant and Research Contractor, Consulting fee and Research support
Gilead: Consultant and Research Contractor, Consulting fee and Research support
Janssen: Consultant, Consulting fee
Merck: Consultant, Consulting fee
Teva: Consultant, Consulting fee
ViiV: Consultant and Research Contractor, Consulting fee and Research support

E. Dejesus, None

P. Echeverría, None

M. Gisslén, BMS, Abbvie, GSK, MSD, Janssen, Gilead: Scientific Advisor and Speaker's Bureau, Consulting fee and Speaker honorarium

M. Honda, None

M. Hughes, None

P. Khabo, Phidisa Project: Employee, Salary

S. Komati, None

P. N. Kumar, Janssen : Grant Investigator and Speaker's Bureau, Consulting fee, Grant recipient, Research grant, Research support and Speaker honorarium
GSK: Grant Investigator and Shareholder, Grant recipient, Research grant and Research support
Merck: Grant Investigator and Shareholder, Grant recipient, Research grant and Research support
ViiV Healthcare: Consultant and Speaker's Bureau, Speaker honorarium
Phizer: Shareholder, stock shareholder
Johnson & Johnson: Shareholder, stock shareholder
Gilead : Shareholder, stock shareholder

S. Lockman, None

R. Macarthur, None

F. Maggiolo, None

A. Matteelli, None

J. M. Miró, None

R. L. Puls, None

S. Riddler, None

P. Sax, AbbVie: Consultant and Scientific Advisor, Consulting fee
BMS: Investigator and Scientific Advisor, Consulting fee and Grant recipient
Gilead: Investigator and Scientific Advisor, Consulting fee and Research support
Merck: Scientific Advisor, Salary
ViiV: Consultant and Investigator, Consulting fee and Research support

J. Sierra-Madero, None

C. Torti, None

J. Lundgren, None

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