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, 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 & 8 others Shinichi Oka, Kathy Petoumenos, Rebekah L Puls, Sharon A Riddler, Paul E Sax, Juan Sierra-Madero, Carlo Torti, Jens D Lundgren

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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.

Original languageEnglish (US)
Pages (from-to)268-80
Number of pages13
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume63
Issue number2
DOIs
StatePublished - Jul 15 2016

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Ritonavir
Reverse Transcriptase Inhibitors
Protease Inhibitors
HIV Infections
Acquired Immunodeficiency Syndrome
Odds Ratio
Databases
Confidence Intervals
Therapeutics

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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. / Borges, Álvaro H; Lundh, Andreas; Tendal, Britta; Bartlett, John A; Clumeck, Nathan; Costagliola, Dominique; Daar, Eric S; Echeverría, Patrícia; Gisslén, Magnus; Huedo-Medina, Tania B; Hughes, Michael D; Huppler Hullsiek, Katherine; Khabo, Paul; Komati, Stephanus; Kumar, Princy; Lockman, Shahin; MacArthur, Rodger D; Maggiolo, Franco; Matteelli, Alberto; Miro, Jose M; Oka, Shinichi; Petoumenos, Kathy; Puls, Rebekah L; Riddler, Sharon A; Sax, Paul E; Sierra-Madero, Juan; Torti, Carlo; Lundgren, Jens D.

In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Vol. 63, No. 2, 15.07.2016, p. 268-80.

Research output: Contribution to journalArticle

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 2016, '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', Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol. 63, no. 2, pp. 268-80. https://doi.org/10.1093/cid/ciw236
Borges, Álvaro H ; Lundh, Andreas ; Tendal, Britta ; Bartlett, John A ; Clumeck, Nathan ; Costagliola, Dominique ; Daar, Eric S ; Echeverría, Patrícia ; Gisslén, Magnus ; Huedo-Medina, Tania B ; Hughes, Michael D ; Huppler Hullsiek, Katherine ; Khabo, Paul ; Komati, Stephanus ; Kumar, Princy ; Lockman, Shahin ; MacArthur, Rodger D ; Maggiolo, Franco ; Matteelli, Alberto ; Miro, Jose M ; Oka, Shinichi ; Petoumenos, Kathy ; Puls, Rebekah L ; Riddler, Sharon A ; Sax, Paul E ; Sierra-Madero, Juan ; Torti, Carlo ; Lundgren, Jens D. / 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. In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2016 ; Vol. 63, No. 2. pp. 268-80.
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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.",
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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 - © 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 - 2016/7/15

Y1 - 2016/7/15

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 - Journal Article

U2 - 10.1093/cid/ciw236

DO - 10.1093/cid/ciw236

M3 - Article

VL - 63

SP - 268

EP - 280

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 2

ER -