Non-nucleoside reverse transcriptase inhibitor- versus ritonavir-boosted protease inhibitor-based regimens for initial treatment of HIV infection: a systematic review and meta-analysis of randomised trials.

Borges ÁH, Lundh A, Tendal B, Bartlett JA, Clumeck N, Costagliola D, Daar ES, Echeverría P, Gisslén M, Huedo-Medina TB, Hughes MD, Huppler Hullsiek K, Khabo P, Komati S, Kumar P, Lockman S, MacArthur RD, Maggiolo F, Matteelli A, Miro JM, Oka S, Petoumenos K, Puls RL, Riddler SA, Sax PE, Sierra-Madero J, Torti C, Lundgren JD
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 Previous studies suggest that non-nucleoside-reverse-transcriptase inhibitors (NNRTI) 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 (up to February 2016) to identify randomised trials comparing 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 increase of CD4 cells at week 48.


 We included 29 trials with 9047 participants. In intention-to-treat analyses, death or progression to AIDS occurred in 226 participants in the NNRTI arm and 221 in the PI/r arm (RR: 1.03 [95%CI: 0.87-1.22], 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:  In this comprehensive meta-analysis, we found no difference in clinical and viro-immunologic outcomes between NNRTI- and PI/r-based therapy.