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

Institut for Klinisk Medicin

12 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Clinical Infectious Diseases
Vol/bind	63
Udgave nummer	2
Sider (fra-til)	268-80
Antal sider	13
ISSN	1058-4838
DOI	https://doi.org/10.1093/cid/ciw236
Status	Udgivet - 2021

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10.1093/cid/ciw236

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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.

I: Clinical Infectious Diseases, Bind 63, Nr. 2, 2021, s. 268-80.

Publikation: Bidrag til tidsskrift › 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, bind 63, nr. 2, s. 268-80. https://doi.org/10.1093/cid/ciw236

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title = "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 = "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.",

keywords = "Journal Article",

author = "Borges, {{\'A}lvaro H} and Andreas Lundh and Britta Tendal and Bartlett, {John A} and Nathan Clumeck and Dominique Costagliola and Daar, {Eric S} and Patr{\'i}cia Echeverr{\'i}a and Magnus Gissl{\'e}n and Huedo-Medina, {Tania B} and Hughes, {Michael D} and {Huppler Hullsiek}, Katherine and Paul Khabo and Stephanus Komati and Princy Kumar and Shahin Lockman and MacArthur, {Rodger D} and Franco Maggiolo and Alberto Matteelli and Miro, {Jose M} and Shinichi Oka and Kathy Petoumenos and Puls, {Rebekah L} and Riddler, {Sharon A} and Sax, {Paul E} and Juan Sierra-Madero and Carlo Torti and Lundgren, {Jens D}",

year = "2021",

doi = "10.1093/cid/ciw236",

language = "English",

volume = "63",

pages = "268--80",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "2",

}

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

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