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Comparison of 48‐week efficacies of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide and nucleoside/nucleotide reverse transcriptase inhibitor‐sparing regimens: a systematic review and network meta‐analysis
Author(s) -
Gallien S,
Massetti M,
Flandre P,
Leleu H,
Descamps D,
Lazaro E
Publication year - 2018
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/hiv.12643
Subject(s) - cobicistat , elvitegravir , tenofovir alafenamide , medicine , raltegravir , emtricitabine , darunavir , ritonavir , pharmacology , viral load , virology , human immunodeficiency virus (hiv) , antiretroviral therapy
Objectives To compare nucleoside/nucleotide reverse transcriptase inhibitor ( NRTI )‐sparing regimens with tenofovir alafenamide ( TAF )‐based combinations in HIV ‐1‐infected adults, we performed a network meta‐analysis ( NMA ) to provide estimates of relative efficacy for these two regimens. Methods A systematic literature review ( SLR ) was performed to identify phase 3/4 randomized controlled clinical trials evaluating the efficacy of commonly used combination antiretroviral therapy ( cART ) including an NRTI backbone or that of commonly used NRTI ‐sparing regimens. A Bayesian random‐effect model was used to compare virological suppression rates at 48 weeks for NRTI ‐sparing regimens and elvitegravir/cobicistat/emtricitabine/ TAF (E/C/F/ TAF ). Results Twenty‐three studies in treatment‐naïve patients identified by the SLR were included in the NMA , including four studies assessing NRTI ‐sparing regimens. In treatment‐naïve patients, the probability of achieving virological suppression at 48 weeks was between 40% and 60% higher with E/C/F/ TAF than with NRTI ‐sparing strategies. The credible interval vs . darunavir/ritonavir ( DVR /r) + raltegravir ( RAL ) and LPV /r monotherapy did not include 1. In the subgroup of naïve patients with viral load < 100 000 HIV ‐1 RNA copies/mL, a credible difference was found between NRTI ‐sparing treatments and E/C/F/ TAF . Studies in treatment‐experienced patients were too heterogeneous to allow for an NMA . Conclusions The NMA results suggest that E/C/F/ TAF represents a more effective option than NRTI ‐sparing regimens in terms of 48‐week efficacy in treatment‐naïve patients. Furthermore, TAF pharmacological properties, as well as tolerability results in clinical studies, suggest a safety profile similar to that of NRTI ‐sparing regimens. Thus, the E/C/F/ TAF combination might represent a more appropriate option than NRTI ‐sparing regimens for initiation of antiretroviral therapy in treatment‐naïve HIV ‐infected patients.