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

doi:10.1093/cid/ciw236

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

Department of Clinical Medicine

12 Citations (Scopus)

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 language	English
Journal	Clinical Infectious Diseases
Volume	63
Issue number	2
Pages (from-to)	268-80
Number of pages	13
ISSN	1058-4838
DOIs	https://doi.org/10.1093/cid/ciw236
Publication status	Published - 2021

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Borges, Á. H., Lundh, A., Tendal, B., Bartlett, J. A., Clumeck, N., Costagliola, D., Daar, E. S., Echeverría, P., Gisslén, M., Huedo-Medina, T. B., Hughes, M. D., Huppler Hullsiek, K., Khabo, P., Komati, S., Kumar, P., Lockman, S., MacArthur, R. D., Maggiolo, F., Matteelli, A., ... Lundgren, J. D. (2021). 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, 63(2), 268-80. https://doi.org/10.1093/cid/ciw236

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 et al.

In: Clinical Infectious Diseases, Vol. 63, No. 2, 2021, p. 268-80.

Research output: Contribution to journal › Review › peer-review

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 2021, '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, vol. 63, no. 2, pp. 268-80. https://doi.org/10.1093/cid/ciw236

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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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year = "2021",

doi = "10.1093/cid/ciw236",

language = "English",

volume = "63",

pages = "268--80",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

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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

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 - Journal Article

U2 - 10.1093/cid/ciw236

DO - 10.1093/cid/ciw236

M3 - Review

C2 - 27090986

SN - 1058-4838

VL - 63

SP - 268

EP - 280

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 2

ER -

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

Abstract

Keywords

UN SDGs

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