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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

Journal article
Authors A. H. Borges
A. Lundh
B. Tendal
J. A. Bartlett
N. Clumeck
D. Costagliola
E. S. Daar
P. Echeverria
Magnus Gisslén
T. B. Huedo-Medina
M. D. Hughes
K. H. Hullsiek
P. Khabo
S. Komati
P. Kumar
S. Lockman
R. D. MacArthur
F. Maggiolo
A. Matteelli
J. M. Miro
S. Oka
K. Petoumenos
R. L. Puls
S. A. Riddler
P. E. Sax
J. Sierra-Madero
C. Torti
J. D. Lundgren
Published in Clinical Infectious Diseases
Volume 63
Issue 2
Pages 268-280
ISSN 1058-4838
Publication year 2016
Published at Institute of Biomedicine, Department of Infectious Medicine
Pages 268-280
Language en
Links dx.doi.org/10.1093/cid/ciw236
Keywords HIV, antiretroviral therapy, protease inhibitor, nonnucleoside reverse transcriptase inhibitor, metaanalysis, antiretroviral therapy, treatment-naive, efavirenz combination, lopinavir-ritonavir, abacavir-lamivudine, plus ritonavir, lopinavir/ritonavir, atazanavir, efficacy, abacavir/lamivudine, Immunology, Infectious Diseases, Microbiology
Subject categories Clinical Medicine

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 meta-analysis 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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