J R Arribas1, P-M Girard2, N Paton3, A Winston4, A-G Marcelin5, D Elbirt6, A Hill7, M B Hadacek8. 1. IdiPAZ, La Paz Hospital, Madrid, Spain. 2. Department of Infectious and Tropical Diseases, Saint Antoine Hospital, AP-HP, and INSERM UMR S 1136, Paris, France. 3. Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore. 4. Department of Medicine, Imperial College, London, UK. 5. Virology, AP-HP, Pitié-Salpêtrière Hospital, INSERM-Sorbonne University, UPMC University of Paris 06, UMR S 1136, Paris, France. 6. AIDS Centre, Kaplan Medical Centre, Rehovot, Israel. 7. Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK. 8. EMEA, Janssen, Issy-les-Moulineux, France.
Abstract
OBJECTIVES: The aim of this analysis was to review the evidence and update a meta-analysis evaluating the efficacy and safety results from randomized controlled trials of ritonavir-boosted protease inhibitor (PI/r) monotherapy. METHODS: A PubMed/EMBASE search was conducted to find randomized trials of PI/r monotherapy vs. triple therapy in patients with HIV-1 RNA suppression at baseline (<50 HIV-1 RNA copies/mL). Rates of virological suppression were analysed using switch-equals-failure and intensification-included endpoints [intent-to-treat (ITT)]. The rate of treatment-emergent resistance mutations, neurocognitive function endpoints, and cerebrospinal fluid (CSF) HIV-1 RNA were also analysed by treatment arm. RESULTS: There were 2303 patients from 13 different randomized clinical trials of darunavir/r monotherapy (n = 784: MONET, MONOI, Monarch and PROTEA), lopinavir/r monotherapy (n = 829: OK pilot, OK-04, KalMo, KALESOLO, KRETA, MOST and DREAM), atazanavir/r monotherapy (n = 103: MODAT), or all three (n = 587: PIVOT). HIV-1 RNA plasma suppression was lower in the PI/r monotherapy arm compared with the triple therapy arm in the switch-equals-failure analysis [difference -8.3%; 95% confidence interval (CI) -11.9 to -4.8%], but not when intensification was included (difference 0.5%; 95% CI -2.5 to 3.6%). Rates of resistance mutations were similar between arms, as was overall neurocognitive function. CONCLUSIONS: PI/r monotherapy showed a higher risk of plasma HIV-1 RNA elevations. However, there was no increased risk of treatment-emergent drug resistance, neurocognitive endpoints did not differ, and HIV-1 RNA suppression rates after intensification were similar between PI/r monotherapy and triple therapy.
OBJECTIVES: The aim of this analysis was to review the evidence and update a meta-analysis evaluating the efficacy and safety results from randomized controlled trials of ritonavir-boosted protease inhibitor (PI/r) monotherapy. METHODS: A PubMed/EMBASE search was conducted to find randomized trials of PI/r monotherapy vs. triple therapy in patients with HIV-1 RNA suppression at baseline (<50 HIV-1 RNA copies/mL). Rates of virological suppression were analysed using switch-equals-failure and intensification-included endpoints [intent-to-treat (ITT)]. The rate of treatment-emergent resistance mutations, neurocognitive function endpoints, and cerebrospinal fluid (CSF) HIV-1 RNA were also analysed by treatment arm. RESULTS: There were 2303 patients from 13 different randomized clinical trials of darunavir/r monotherapy (n = 784: MONET, MONOI, Monarch and PROTEA), lopinavir/r monotherapy (n = 829: OK pilot, OK-04, KalMo, KALESOLO, KRETA, MOST and DREAM), atazanavir/r monotherapy (n = 103: MODAT), or all three (n = 587: PIVOT). HIV-1 RNA plasma suppression was lower in the PI/r monotherapy arm compared with the triple therapy arm in the switch-equals-failure analysis [difference -8.3%; 95% confidence interval (CI) -11.9 to -4.8%], but not when intensification was included (difference 0.5%; 95% CI -2.5 to 3.6%). Rates of resistance mutations were similar between arms, as was overall neurocognitive function. CONCLUSIONS:PI/r monotherapy showed a higher risk of plasma HIV-1 RNA elevations. However, there was no increased risk of treatment-emergent drug resistance, neurocognitive endpoints did not differ, and HIV-1 RNA suppression rates after intensification were similar between PI/r monotherapy and triple therapy.
Authors: Jordan M Meyers; Muthukumar Ramanathan; Ronald L Shanderson; Laura Donohue; Ian Ferguson; Margaret G Guo; Deepti S Rao; Weili Miao; David Reynolds; Xue Yang; Yang Zhao; Yen-Yu Yang; Yinsheng Wang; Paul A Khavari Journal: bioRxiv Date: 2021-02-23
Authors: Alicia Gutierrez-Valencia; Maria Trujillo-Rodriguez; Tamara Fernandez-Magdaleno; Nuria Espinosa; Pompeyo Viciana; Luis F López-Cortés Journal: J Int AIDS Soc Date: 2018-02 Impact factor: 5.396