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

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.

• Authors: Álvaro H Borges, Andreas Lundh, Britta Tendal, John A Bartlett, Nathan Clumeck, Dominique Costagliola, Eric S Daar, Patrícia Echeverría, Magnus Gisslén, Tania B Huedo-Medina, Michael D Hughes, Katherine Huppler Hullsiek, Paul Khabo, Stephanus Komati, Princy Kumar, Shahin Lockman, Rodger D MacArthur, Franco Maggiolo, Alberto Matteelli, Jose M Miro, Shinichi Oka, Kathy Petoumenos, Rebekah L Puls, Sharon A Riddler, Paul E Sax, Juan Sierra-Madero, Carlo Torti, Jens D Lundgren
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 63 Issue 2 Pg. 268-80 (07 15 2016) ISSN: 1537-6591 [Electronic] United States
• PMID: 27090986 (Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)
• Copyright: © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected].

Chemical References

• Anti-HIV Agents
• HIV Protease Inhibitors
• Reverse Transcriptase Inhibitors
• Ritonavir

Topics

• Anti-HIV Agents (therapeutic use)
• Drug Therapy, Combination
• HIV Infections (drug therapy)
• HIV Protease Inhibitors (therapeutic use)
• Humans
• Reverse Transcriptase Inhibitors (therapeutic use)
• Ritonavir (therapeutic use)