Individual patient data meta-analysis of randomized controlled trials of dual therapy with a boosted PI plus lamivudine for maintenance of virological suppression: GeSIDA study 9717

J. A. Perez-Molina; F. Pulido; S. Di Giambenedetto; E. Ribera; S. Moreno; J. Zamora; C. Coscia; B. Alejos; J. Pitch; J. M. Gatell; A. De Luca; J. R. Arribas

doi:10.1093/jac/dky299

Individual patient data meta-analysis of randomized controlled trials of dual therapy with a boosted PI plus lamivudine for maintenance of virological suppression: GeSIDA study 9717

J. A. Perez-Molina^*, F. Pulido, S. Di Giambenedetto, E. Ribera, S. Moreno, J. Zamora, C. Coscia, B. Alejos, J. Pitch, J. M. Gatell, A. De Luca, J. R. Arribas

^*Corresponding author for this work

Metabolism and Systems Research

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

17 Citations (Scopus)

Abstract

Background: Dual therapy (DT) with a ritonavir-boosted PI (PI/r) plus lamivudine has proven non-inferior (12% margin) to triple therapy (TT) with PI/r plus two nucleos(t)ide reverse transcriptase inhibitors [N(t)RTIs] in four clinical trials. It remains unclear whether DT is non-inferior based on the US FDA endpoint (virological failure with a margin of 4%) or in specific subgroups. Methods: We performed a systematic search (January 1990 to March 2017) of randomized controlled trials that compared switching of maintenance ART from TT to DT. The principal investigators were contacted and agreed to share study databases. The primary endpoint was non-inferiority of DT to TT based on the current FDA endpoint (4% non-inferiority margin for virological failure at week 48). We also analysed whether efficacy was modified by gender, active HCV infection and type of PI. Effect estimates and 95% CIs were calculated using generalized estimating equation-based models. Results: We found 881 references that yielded eight articles corresponding to four clinical trials (1051 patients). At week 48, 4% of patients on DT versus 3.04% on TT had experienced virological failure (difference 0.9%; 95% CI –1.2% to 3.1%), and 84.7% of patients on DT versus 83.2% on TT had,50 copies of HIV RNA/mL (FDA snapshot algorithm) (difference 1.4%; 95% CI –2.8% to 5.8%). Gender, active HCV infection and type of PI had no effect on differences in treatment efficacy between DT and TT. Conclusions: DT was non-inferior to TT using both current and past FDA endpoints. The efficacy of DT was not influenced by gender, active HCV infection status, or type of PI.

Original language	English
Pages (from-to)	2927-2935
Number of pages	9
Journal	Journal of Antimicrobial Chemotherapy
Volume	73
Issue number	11
DOIs	https://doi.org/10.1093/jac/dky299
Publication status	Published - 1 Nov 2018

Bibliographical note

Funding Information:
We thank the personnel of Fundación SEIMC-GeSIDA for their support and the Spanish AIDS Research Network RD16/0025/0007 - ISCIII, FEDER. We are grateful to all clinical trial participants.

Funding Information:
J. A. P-M. reports personal fees from Fundación SEIMC-GeSIDA, during the conduct of the study; personal fees from ViiV, MSD and Janssen, grants from MSD, outside the submitted work. F. P. reports personal fees from Abbvie, Janssen, Gilead, MSD and ViiV, outside the submitted work. S. D. G. reports speaker honoraria from BMS Gilead, Janssen, ViiV and Merck. E. R. reports non-financial support from Abbvie, personal fees and non-financial support from Bristol-Myers Squibb, grants, personal fees and non-financial support from Gilead, Janssen, Merck Sharp and Dohme and ViiV, outside the submitted work. S. M. reports grants and other from Gilead, Janssen, MSD and Viiv Healthcare, outside the submitted work. J. Z. reports grants from SEIMC-GeSIDA foundation, during the conduct of the study. J. M. G. reports grants and personal fees from ViiV Healthcare, MSD, Janssen and Gilead Sciences, outside the submitted work. A. D. L. reports grants from ViiV Healthcare and Gilead Sciences, personal fees from ViiV Healthcare, Gilead Sciences, Janssen Cilag and Merck Sharp and Dohme, outside the submitted work. J. R. A. reports personal fees from Fundación SEIMC GESIDA, during the conduct of the study; personal fees from Gilead, ViiV, MSD, Janssen, grants from Janssen, Gilead, outside the submitted work. The remaining authors have none to declare.

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

ASJC Scopus subject areas

Pharmacology
Microbiology (medical)
Pharmacology (medical)
Infectious Diseases

UN SDGs

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

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10.1093/jac/dky299

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Perez-Molina, J. A., Pulido, F., Di Giambenedetto, S., Ribera, E., Moreno, S., Zamora, J., Coscia, C., Alejos, B., Pitch, J., Gatell, J. M., De Luca, A., & Arribas, J. R. (2018). Individual patient data meta-analysis of randomized controlled trials of dual therapy with a boosted PI plus lamivudine for maintenance of virological suppression: GeSIDA study 9717. Journal of Antimicrobial Chemotherapy, 73(11), 2927-2935. https://doi.org/10.1093/jac/dky299

@article{2511c3d8a83f4e9bbd24e031c93c631a,

title = "Individual patient data meta-analysis of randomized controlled trials of dual therapy with a boosted PI plus lamivudine for maintenance of virological suppression: GeSIDA study 9717",

abstract = "Background: Dual therapy (DT) with a ritonavir-boosted PI (PI/r) plus lamivudine has proven non-inferior (12% margin) to triple therapy (TT) with PI/r plus two nucleos(t)ide reverse transcriptase inhibitors [N(t)RTIs] in four clinical trials. It remains unclear whether DT is non-inferior based on the US FDA endpoint (virological failure with a margin of 4%) or in specific subgroups. Methods: We performed a systematic search (January 1990 to March 2017) of randomized controlled trials that compared switching of maintenance ART from TT to DT. The principal investigators were contacted and agreed to share study databases. The primary endpoint was non-inferiority of DT to TT based on the current FDA endpoint (4% non-inferiority margin for virological failure at week 48). We also analysed whether efficacy was modified by gender, active HCV infection and type of PI. Effect estimates and 95% CIs were calculated using generalized estimating equation-based models. Results: We found 881 references that yielded eight articles corresponding to four clinical trials (1051 patients). At week 48, 4% of patients on DT versus 3.04% on TT had experienced virological failure (difference 0.9%; 95% CI –1.2% to 3.1%), and 84.7% of patients on DT versus 83.2% on TT had,50 copies of HIV RNA/mL (FDA snapshot algorithm) (difference 1.4%; 95% CI –2.8% to 5.8%). Gender, active HCV infection and type of PI had no effect on differences in treatment efficacy between DT and TT. Conclusions: DT was non-inferior to TT using both current and past FDA endpoints. The efficacy of DT was not influenced by gender, active HCV infection status, or type of PI.",

author = "Perez-Molina, {J. A.} and F. Pulido and {Di Giambenedetto}, S. and E. Ribera and S. Moreno and J. Zamora and C. Coscia and B. Alejos and J. Pitch and Gatell, {J. M.} and {De Luca}, A. and Arribas, {J. R.}",

note = "Funding Information: We thank the personnel of Fundaci{\'o}n SEIMC-GeSIDA for their support and the Spanish AIDS Research Network RD16/0025/0007 - ISCIII, FEDER. We are grateful to all clinical trial participants. Funding Information: J. A. P-M. reports personal fees from Fundaci{\'o}n SEIMC-GeSIDA, during the conduct of the study; personal fees from ViiV, MSD and Janssen, grants from MSD, outside the submitted work. F. P. reports personal fees from Abbvie, Janssen, Gilead, MSD and ViiV, outside the submitted work. S. D. G. reports speaker honoraria from BMS Gilead, Janssen, ViiV and Merck. E. R. reports non-financial support from Abbvie, personal fees and non-financial support from Bristol-Myers Squibb, grants, personal fees and non-financial support from Gilead, Janssen, Merck Sharp and Dohme and ViiV, outside the submitted work. S. M. reports grants and other from Gilead, Janssen, MSD and Viiv Healthcare, outside the submitted work. J. Z. reports grants from SEIMC-GeSIDA foundation, during the conduct of the study. J. M. G. reports grants and personal fees from ViiV Healthcare, MSD, Janssen and Gilead Sciences, outside the submitted work. A. D. L. reports grants from ViiV Healthcare and Gilead Sciences, personal fees from ViiV Healthcare, Gilead Sciences, Janssen Cilag and Merck Sharp and Dohme, outside the submitted work. J. R. A. reports personal fees from Fundaci{\'o}n SEIMC GESIDA, during the conduct of the study; personal fees from Gilead, ViiV, MSD, Janssen, grants from Janssen, Gilead, outside the submitted work. The remaining authors have none to declare. Publisher Copyright: {\textcopyright} The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.",

year = "2018",

month = nov,

day = "1",

doi = "10.1093/jac/dky299",

language = "English",

volume = "73",

pages = "2927--2935",

journal = "Journal of Antimicrobial Chemotherapy",

issn = "0305-7453",

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Perez-Molina, JA, Pulido, F, Di Giambenedetto, S, Ribera, E, Moreno, S, Zamora, J, Coscia, C, Alejos, B, Pitch, J, Gatell, JM, De Luca, A & Arribas, JR 2018, 'Individual patient data meta-analysis of randomized controlled trials of dual therapy with a boosted PI plus lamivudine for maintenance of virological suppression: GeSIDA study 9717', Journal of Antimicrobial Chemotherapy, vol. 73, no. 11, pp. 2927-2935. https://doi.org/10.1093/jac/dky299

Individual patient data meta-analysis of randomized controlled trials of dual therapy with a boosted PI plus lamivudine for maintenance of virological suppression: GeSIDA study 9717. / Perez-Molina, J. A.; Pulido, F.; Di Giambenedetto, S. et al.
In: Journal of Antimicrobial Chemotherapy, Vol. 73, No. 11, 01.11.2018, p. 2927-2935.

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

TY - JOUR

T1 - Individual patient data meta-analysis of randomized controlled trials of dual therapy with a boosted PI plus lamivudine for maintenance of virological suppression

T2 - GeSIDA study 9717

AU - Perez-Molina, J. A.

AU - Pulido, F.

AU - Di Giambenedetto, S.

AU - Ribera, E.

AU - Moreno, S.

AU - Zamora, J.

AU - Coscia, C.

AU - Alejos, B.

AU - Pitch, J.

AU - Gatell, J. M.

AU - De Luca, A.

AU - Arribas, J. R.

N1 - Funding Information: We thank the personnel of Fundación SEIMC-GeSIDA for their support and the Spanish AIDS Research Network RD16/0025/0007 - ISCIII, FEDER. We are grateful to all clinical trial participants. Funding Information: J. A. P-M. reports personal fees from Fundación SEIMC-GeSIDA, during the conduct of the study; personal fees from ViiV, MSD and Janssen, grants from MSD, outside the submitted work. F. P. reports personal fees from Abbvie, Janssen, Gilead, MSD and ViiV, outside the submitted work. S. D. G. reports speaker honoraria from BMS Gilead, Janssen, ViiV and Merck. E. R. reports non-financial support from Abbvie, personal fees and non-financial support from Bristol-Myers Squibb, grants, personal fees and non-financial support from Gilead, Janssen, Merck Sharp and Dohme and ViiV, outside the submitted work. S. M. reports grants and other from Gilead, Janssen, MSD and Viiv Healthcare, outside the submitted work. J. Z. reports grants from SEIMC-GeSIDA foundation, during the conduct of the study. J. M. G. reports grants and personal fees from ViiV Healthcare, MSD, Janssen and Gilead Sciences, outside the submitted work. A. D. L. reports grants from ViiV Healthcare and Gilead Sciences, personal fees from ViiV Healthcare, Gilead Sciences, Janssen Cilag and Merck Sharp and Dohme, outside the submitted work. J. R. A. reports personal fees from Fundación SEIMC GESIDA, during the conduct of the study; personal fees from Gilead, ViiV, MSD, Janssen, grants from Janssen, Gilead, outside the submitted work. The remaining authors have none to declare. Publisher Copyright: © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Background: Dual therapy (DT) with a ritonavir-boosted PI (PI/r) plus lamivudine has proven non-inferior (12% margin) to triple therapy (TT) with PI/r plus two nucleos(t)ide reverse transcriptase inhibitors [N(t)RTIs] in four clinical trials. It remains unclear whether DT is non-inferior based on the US FDA endpoint (virological failure with a margin of 4%) or in specific subgroups. Methods: We performed a systematic search (January 1990 to March 2017) of randomized controlled trials that compared switching of maintenance ART from TT to DT. The principal investigators were contacted and agreed to share study databases. The primary endpoint was non-inferiority of DT to TT based on the current FDA endpoint (4% non-inferiority margin for virological failure at week 48). We also analysed whether efficacy was modified by gender, active HCV infection and type of PI. Effect estimates and 95% CIs were calculated using generalized estimating equation-based models. Results: We found 881 references that yielded eight articles corresponding to four clinical trials (1051 patients). At week 48, 4% of patients on DT versus 3.04% on TT had experienced virological failure (difference 0.9%; 95% CI –1.2% to 3.1%), and 84.7% of patients on DT versus 83.2% on TT had,50 copies of HIV RNA/mL (FDA snapshot algorithm) (difference 1.4%; 95% CI –2.8% to 5.8%). Gender, active HCV infection and type of PI had no effect on differences in treatment efficacy between DT and TT. Conclusions: DT was non-inferior to TT using both current and past FDA endpoints. The efficacy of DT was not influenced by gender, active HCV infection status, or type of PI.

AB - Background: Dual therapy (DT) with a ritonavir-boosted PI (PI/r) plus lamivudine has proven non-inferior (12% margin) to triple therapy (TT) with PI/r plus two nucleos(t)ide reverse transcriptase inhibitors [N(t)RTIs] in four clinical trials. It remains unclear whether DT is non-inferior based on the US FDA endpoint (virological failure with a margin of 4%) or in specific subgroups. Methods: We performed a systematic search (January 1990 to March 2017) of randomized controlled trials that compared switching of maintenance ART from TT to DT. The principal investigators were contacted and agreed to share study databases. The primary endpoint was non-inferiority of DT to TT based on the current FDA endpoint (4% non-inferiority margin for virological failure at week 48). We also analysed whether efficacy was modified by gender, active HCV infection and type of PI. Effect estimates and 95% CIs were calculated using generalized estimating equation-based models. Results: We found 881 references that yielded eight articles corresponding to four clinical trials (1051 patients). At week 48, 4% of patients on DT versus 3.04% on TT had experienced virological failure (difference 0.9%; 95% CI –1.2% to 3.1%), and 84.7% of patients on DT versus 83.2% on TT had,50 copies of HIV RNA/mL (FDA snapshot algorithm) (difference 1.4%; 95% CI –2.8% to 5.8%). Gender, active HCV infection and type of PI had no effect on differences in treatment efficacy between DT and TT. Conclusions: DT was non-inferior to TT using both current and past FDA endpoints. The efficacy of DT was not influenced by gender, active HCV infection status, or type of PI.

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U2 - 10.1093/jac/dky299

DO - 10.1093/jac/dky299

M3 - Article

C2 - 30085184

AN - SCOPUS:85055151233

SN - 0305-7453

VL - 73

SP - 2927

EP - 2935

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 11

ER -

Individual patient data meta-analysis of randomized controlled trials of dual therapy with a boosted PI plus lamivudine for maintenance of virological suppression: GeSIDA study 9717

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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