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Meta-Analysis
. 2016 Jul 15;63(2):268-80.
doi: 10.1093/cid/ciw236. Epub 2016 Apr 18.

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

Álvaro H Borges  1 , Andreas Lundh  2 , Britta Tendal  3 , John A Bartlett  4 , Nathan Clumeck  5 , Dominique Costagliola  6 , Eric S Daar  7 , Patrícia Echeverría  8 , Magnus Gisslén  9 , Tania B Huedo-Medina  10 , Michael D Hughes  11 , Katherine Huppler Hullsiek  12 , Paul Khabo  13 , Stephanus Komati  13 , Princy Kumar  14 , Shahin Lockman  15 , Rodger D MacArthur  16 , Franco Maggiolo  17 , Alberto Matteelli  18 , Jose M Miro  19 , Shinichi Oka  20 , Kathy Petoumenos  21 , Rebekah L Puls  21 , Sharon A Riddler  22 , Paul E Sax  23 , Juan Sierra-Madero  24 , Carlo Torti  25 , Jens D Lundgren  1
Affiliations
Meta-Analysis

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

Álvaro H Borges et al. Clin Infect Dis. .

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.

Keywords: HIV; antiretroviral therapy; metaanalysis; nonnucleoside reverse transcriptase inhibitor; protease inhibitor.

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Figures

Figure 1.
Figure 1.
Death or progression to AIDS. Abbreviations: CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel; NNRTI, nonnucleoside reverse-transcriptase inhibitor; PI, protease inhibitor.
Figure 2.
Figure 2.
All-cause deaths. Abbreviations: CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel; NNRTI, nonnucleoside reverse-transcriptase inhibitor; PI, protease inhibitor.
Figure 3.
Figure 3.
Progression to AIDS. Abbreviations: CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel; NNRTI, nonnucleoside reverse-transcriptase inhibitor; PI, protease inhibitor.
Figure 4.
Figure 4.
Virologic suppression 48 weeks after treatment initiation. Abbreviations: CI, confidence interval; df, degrees of freedom; M-H, Mantel-Haenszel; NNRTI, nonnucleoside reverse-transcriptase inhibitor; PI, protease inhibitor.
Figure 5.
Figure 5.
Mean CD4+ count difference 48 weeks after treatment initiation. Abbreviations: CI, confidence interval; df, degrees of freedom; IV, inverse variance; NNRTI, nonnucleoside reverse-transcriptase inhibitor; PI, protease inhibitor; SD, standard deviation.
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