Week 48 efficacy and central nervous system analysis of darunavir/ritonavir monotherapy versus darunavir/ritonavir with two nucleoside analogues

Andrea Antinori; Amanda Clarke; Veronika Svedhem-Johansson; José R Arribas; Alejandro Arenas-Pinto; Jan Fehr; Jan Gerstoft; Andrzej Horban; Bonaventura Clotet; Diego Ripamonti; Pierre-Marie Girard; Andrew M Hill; Christiane Moecklinghoff

doi:10.1097/QAD.0000000000000778

Week 48 efficacy and central nervous system analysis of darunavir/ritonavir monotherapy versus darunavir/ritonavir with two nucleoside analogues

Andrea Antinori, Amanda Clarke, Veronika Svedhem-Johansson, José R Arribas, Alejandro Arenas-Pinto, Jan Fehr, Jan Gerstoft, Andrzej Horban, Bonaventura Clotet, Diego Ripamonti, Pierre-Marie Girard, Andrew M Hill, Christiane Moecklinghoff

Department of Clinical Medicine

33 Citations (Scopus)

Abstract

Background: In previous studies in virologically suppressed patients, protease inhibitor monotherapy has shown trends for more low-level elevations in HIV-1 RNA compared with triple therapy, but no increase in the risk of drug resistance. Methods: A total of 273 patients with HIV-1 RNA less than 50 copies/ml on first-line antiretrovirals switched to darunavir/ritonavir (DRV/r) 800/100mg once daily, either as monotherapy (n=37) or as triple therapy with two nucleoside analogues (n=136). Treatment failure was defined as HIV-1 RNA levels 50 copies/ml or above, or discontinuation of study treatment by week 48 (FDA Snapshot algorithm). Results: Patients were 83% male and 88% white, with mean age 42 years. In the primary efficacy analysis, HIV-1 RNA less than 50 copies/ml by week 48 [intention-Totreat (ITT)] was 118 of 137 (86%) in the DRV/r monotherapy arm versus 129 of 136 (95%) in the triple therapy arm (difference=-8.7%, 95% confidence interval -15.50, -1.80). In a post-hoc analysis, for patients with nadir CD4 cell count 200 cells/ml or above, rates of HIV-1 RNA suppression were 91 of 96 (95%) in the DRV/r monotherapy arm and 100 of 106 (94%) in the triple therapy arm. There was no difference in neurocognitive function or the risk of neuropsychiatric adverse events between DRV/r monotherapy and triple therapy. Two patients in the monotherapy arm with CD4 nadir less than 200 cells/ml developed viraemia in both cerebrospinal fluid (CSF) and plasma, with one symptomatic case. Conclusions: In this study for patients with HIV-1 RNA less than 50 copies/ml at baseline, switching to DRV/r monotherapy showed lower efficacy versus triple therapy at week 48 in the primary ITT switch equals failure analysis, with two cases of viraemia in the CSF in the protease inhibitor monotherapy arm.

Original language	English
Journal	AIDS (Year)
Volume	29
Issue number	14
Pages (from-to)	1811-20
Number of pages	10
ISSN	1350-2840
DOIs	https://doi.org/10.1097/QAD.0000000000000778
Publication status	Published - 10 Sept 2015

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10.1097/QAD.0000000000000778

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Antinori, A., Clarke, A., Svedhem-Johansson, V., Arribas, J. R., Arenas-Pinto, A., Fehr, J., Gerstoft, J., Horban, A., Clotet, B., Ripamonti, D., Girard, P-M., Hill, A. M., & Moecklinghoff, C. (2015). Week 48 efficacy and central nervous system analysis of darunavir/ritonavir monotherapy versus darunavir/ritonavir with two nucleoside analogues. AIDS (Year), 29(14), 1811-20. https://doi.org/10.1097/QAD.0000000000000778

Antinori, A, Clarke, A, Svedhem-Johansson, V, Arribas, JR, Arenas-Pinto, A, Fehr, J, Gerstoft, J, Horban, A, Clotet, B, Ripamonti, D, Girard, P-M, Hill, AM & Moecklinghoff, C 2015, 'Week 48 efficacy and central nervous system analysis of darunavir/ritonavir monotherapy versus darunavir/ritonavir with two nucleoside analogues', AIDS (Year), vol. 29, no. 14, pp. 1811-20. https://doi.org/10.1097/QAD.0000000000000778

@article{2a13927409364447bab07347ab9e9395,

title = "Week 48 efficacy and central nervous system analysis of darunavir/ritonavir monotherapy versus darunavir/ritonavir with two nucleoside analogues",

abstract = "Background: In previous studies in virologically suppressed patients, protease inhibitor monotherapy has shown trends for more low-level elevations in HIV-1 RNA compared with triple therapy, but no increase in the risk of drug resistance. Methods: A total of 273 patients with HIV-1 RNA less than 50 copies/ml on first-line antiretrovirals switched to darunavir/ritonavir (DRV/r) 800/100mg once daily, either as monotherapy (n=37) or as triple therapy with two nucleoside analogues (n=136). Treatment failure was defined as HIV-1 RNA levels 50 copies/ml or above, or discontinuation of study treatment by week 48 (FDA Snapshot algorithm). Results: Patients were 83% male and 88% white, with mean age 42 years. In the primary efficacy analysis, HIV-1 RNA less than 50 copies/ml by week 48 [intention-Totreat (ITT)] was 118 of 137 (86%) in the DRV/r monotherapy arm versus 129 of 136 (95%) in the triple therapy arm (difference=-8.7%, 95% confidence interval -15.50, -1.80). In a post-hoc analysis, for patients with nadir CD4 cell count 200 cells/ml or above, rates of HIV-1 RNA suppression were 91 of 96 (95%) in the DRV/r monotherapy arm and 100 of 106 (94%) in the triple therapy arm. There was no difference in neurocognitive function or the risk of neuropsychiatric adverse events between DRV/r monotherapy and triple therapy. Two patients in the monotherapy arm with CD4 nadir less than 200 cells/ml developed viraemia in both cerebrospinal fluid (CSF) and plasma, with one symptomatic case. Conclusions: In this study for patients with HIV-1 RNA less than 50 copies/ml at baseline, switching to DRV/r monotherapy showed lower efficacy versus triple therapy at week 48 in the primary ITT switch equals failure analysis, with two cases of viraemia in the CSF in the protease inhibitor monotherapy arm.",

author = "Andrea Antinori and Amanda Clarke and Veronika Svedhem-Johansson and Arribas, {Jos{\'e} R} and Alejandro Arenas-Pinto and Jan Fehr and Jan Gerstoft and Andrzej Horban and Bonaventura Clotet and Diego Ripamonti and Pierre-Marie Girard and Hill, {Andrew M} and Christiane Moecklinghoff",

year = "2015",

month = sep,

day = "10",

doi = "10.1097/QAD.0000000000000778",

language = "English",

volume = "29",

pages = "1811--20",

journal = "AIDS, Supplement",

issn = "1350-2840",

publisher = "Lippincott Williams & Wilkins, Ltd.",

number = "14",

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TY - JOUR

T1 - Week 48 efficacy and central nervous system analysis of darunavir/ritonavir monotherapy versus darunavir/ritonavir with two nucleoside analogues

AU - Antinori, Andrea

AU - Clarke, Amanda

AU - Svedhem-Johansson, Veronika

AU - Arribas, José R

AU - Arenas-Pinto, Alejandro

AU - Fehr, Jan

AU - Gerstoft, Jan

AU - Horban, Andrzej

AU - Clotet, Bonaventura

AU - Ripamonti, Diego

AU - Girard, Pierre-Marie

AU - Hill, Andrew M

AU - Moecklinghoff, Christiane

PY - 2015/9/10

Y1 - 2015/9/10

N2 - Background: In previous studies in virologically suppressed patients, protease inhibitor monotherapy has shown trends for more low-level elevations in HIV-1 RNA compared with triple therapy, but no increase in the risk of drug resistance. Methods: A total of 273 patients with HIV-1 RNA less than 50 copies/ml on first-line antiretrovirals switched to darunavir/ritonavir (DRV/r) 800/100mg once daily, either as monotherapy (n=37) or as triple therapy with two nucleoside analogues (n=136). Treatment failure was defined as HIV-1 RNA levels 50 copies/ml or above, or discontinuation of study treatment by week 48 (FDA Snapshot algorithm). Results: Patients were 83% male and 88% white, with mean age 42 years. In the primary efficacy analysis, HIV-1 RNA less than 50 copies/ml by week 48 [intention-Totreat (ITT)] was 118 of 137 (86%) in the DRV/r monotherapy arm versus 129 of 136 (95%) in the triple therapy arm (difference=-8.7%, 95% confidence interval -15.50, -1.80). In a post-hoc analysis, for patients with nadir CD4 cell count 200 cells/ml or above, rates of HIV-1 RNA suppression were 91 of 96 (95%) in the DRV/r monotherapy arm and 100 of 106 (94%) in the triple therapy arm. There was no difference in neurocognitive function or the risk of neuropsychiatric adverse events between DRV/r monotherapy and triple therapy. Two patients in the monotherapy arm with CD4 nadir less than 200 cells/ml developed viraemia in both cerebrospinal fluid (CSF) and plasma, with one symptomatic case. Conclusions: In this study for patients with HIV-1 RNA less than 50 copies/ml at baseline, switching to DRV/r monotherapy showed lower efficacy versus triple therapy at week 48 in the primary ITT switch equals failure analysis, with two cases of viraemia in the CSF in the protease inhibitor monotherapy arm.

AB - Background: In previous studies in virologically suppressed patients, protease inhibitor monotherapy has shown trends for more low-level elevations in HIV-1 RNA compared with triple therapy, but no increase in the risk of drug resistance. Methods: A total of 273 patients with HIV-1 RNA less than 50 copies/ml on first-line antiretrovirals switched to darunavir/ritonavir (DRV/r) 800/100mg once daily, either as monotherapy (n=37) or as triple therapy with two nucleoside analogues (n=136). Treatment failure was defined as HIV-1 RNA levels 50 copies/ml or above, or discontinuation of study treatment by week 48 (FDA Snapshot algorithm). Results: Patients were 83% male and 88% white, with mean age 42 years. In the primary efficacy analysis, HIV-1 RNA less than 50 copies/ml by week 48 [intention-Totreat (ITT)] was 118 of 137 (86%) in the DRV/r monotherapy arm versus 129 of 136 (95%) in the triple therapy arm (difference=-8.7%, 95% confidence interval -15.50, -1.80). In a post-hoc analysis, for patients with nadir CD4 cell count 200 cells/ml or above, rates of HIV-1 RNA suppression were 91 of 96 (95%) in the DRV/r monotherapy arm and 100 of 106 (94%) in the triple therapy arm. There was no difference in neurocognitive function or the risk of neuropsychiatric adverse events between DRV/r monotherapy and triple therapy. Two patients in the monotherapy arm with CD4 nadir less than 200 cells/ml developed viraemia in both cerebrospinal fluid (CSF) and plasma, with one symptomatic case. Conclusions: In this study for patients with HIV-1 RNA less than 50 copies/ml at baseline, switching to DRV/r monotherapy showed lower efficacy versus triple therapy at week 48 in the primary ITT switch equals failure analysis, with two cases of viraemia in the CSF in the protease inhibitor monotherapy arm.

U2 - 10.1097/QAD.0000000000000778

DO - 10.1097/QAD.0000000000000778

M3 - Journal article

C2 - 26372387

SN - 1350-2840

VL - 29

SP - 1811

EP - 1820

JO - AIDS, Supplement

JF - AIDS, Supplement

IS - 14

ER -

Week 48 efficacy and central nervous system analysis of darunavir/ritonavir monotherapy versus darunavir/ritonavir with two nucleoside analogues

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