TY - JOUR
T1 - Nonnucleoside reverse-transcriptase inhibitor- vs ritonavir-boosted protease inhibitor-based regimens for initial treatment of HIV Infection
T2 - A systematic review and metaanalysis of randomized trials
AU - Borges, Álvaro H.
AU - Lundh, Andreas
AU - Tendal, Britta
AU - Bartlett, John A.
AU - Clumeck, Nathan
AU - Costagliola, Dominique
AU - Daar, Eric S.
AU - Echeverría, Patrícia
AU - Gisslén, Magnus
AU - Huedo-Medina, Tania B.
AU - Hughes, Michael D.
AU - Huppler Hullsiek, Katherine
AU - Khabo, Paul
AU - Komati, Stephanus
AU - Kumar, Princy
AU - Lockman, Shahin
AU - MacArthur, Rodger D.
AU - Maggiolo, Franco
AU - Matteelli, Alberto
AU - Miro, Jose M.
AU - Oka, Shinichi
AU - Petoumenos, Kathy
AU - Puls, Rebekah L.
AU - Riddler, Sharon A.
AU - Sax, Paul E.
AU - Sierra-Madero, Juan
AU - Torti, Carlo
AU - Lundgren, Jens D.
N1 - Funding Information:
This study was supported by the Research Council at Rigshospitalet and by the Danish National Research Foundation (grant DNRF126). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of this manuscript.
Publisher Copyright:
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Antiretroviral therapy
KW - HIV
KW - Metaanalysis
KW - Nonnucleoside reverse transcriptase inhibitor
KW - Protease inhibitor
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U2 - 10.1093/cid/ciw236
DO - 10.1093/cid/ciw236
M3 - Article
C2 - 27090986
AN - SCOPUS:85007419657
SN - 1058-4838
VL - 63
SP - 268
EP - 280
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 2
ER -