C Spertilli Raffaelli1,2, B Rossetti2,3, L Paglicci1,2, M Colafigli3, G Punzi4, V Borghi5, M Pecorari6, M M Santoro7, G Penco8, A Antinori9, M Zazzi1, A De Luca1,2, G Zanelli1,2. 1. Department of Medical Biotechnologies, University of Siena, Siena, Italy. 2. University Division of Infectious Diseases, Hospital Department of Specialized and Internal Medicine, Siena University Hospital, Siena, Italy. 3. Clinic of Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy. 4. Virology, Bari Hospital, Bari, Italy. 5. Infectious Diseases Unit, Modena Hospital, Modena, Italy. 6. Microbiology and Virology Unit, University Hospital, Modena, Italy. 7. Department of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Rome, Italy. 8. Infectious Diseases Department, Ente Ospedaliero Ospedali Galliera, Genoa, Italy. 9. Infectious Diseases Department, INMI 'Lazzaro Spallanzani', Rome, Italy.
Abstract
Objectives: To examine the impact of transmitted drug resistance (TDR) on response to first-line regimens with integrase strand transfer inhibitors (INSTIs) or boosted protease inhibitors (bPIs). Methods: From an Italian observational database (ARCA) we selected HIV-1-infected drug-naive patients starting two NRTIs and either an INSTI or a bPI, with an available pre-ART resistance genotype. The endpoint was virological failure (VF; plasma HIV-1 RNA >200 copies/mL after week 24). WHO surveillance drug resistance mutations and the Stanford algorithm were used to classify patients into three resistance categories: no TDR (A), TDR but fully-active ART prescribed (B), TDR and at least low-level resistance to one or more prescribed drug (C). Results: We included 1365 patients with a median follow-up of 96 weeks (IQR 54-110): 1205 (88.3%) starting bPI and 160 (11.7%) INSTI. Prevalence of TDR was 6.1%, 12.5%, 2.6% and 0% for NRTI, NNRTI, bPI and INSTI, respectively. Cumulative Kaplan-Meier estimates for VF at 48 weeks were 11% (95% CI 10.1%-11.9%) for the bPI group and 7.7% (95% CI 5.4%-10%) for the INSTI group. In the INSTI group, cumulative estimates for VF at 48 weeks were 6% (95% CI 4%-8%) in resistance category A, 5% (95% CI 1%-10%) in B and 50% (95% CI 30%-70%) in C (P < 0.001). Resistance category C [versus A, adjusted hazard ratio (aHR) 12.6, 95% CI 3.2-49.8, P < 0.001] and nadir CD4 (+100 cells/mm3, aHR 0.6, 95% CI 0.4-0.9, P = 0.03) predicted VF. In the bPI group, VF rates were not influenced by baseline resistance. Conclusions: Our data support the need for NRTI resistance genotyping in patients starting an INSTI-based first-line ART.
Objectives: To examine the impact of transmitted drug resistance (TDR) on response to first-line regimens with integrase strand transfer inhibitors (INSTIs) or boosted protease inhibitors (bPIs). Methods: From an Italian observational database (ARCA) we selected HIV-1-infected drug-naivepatients starting two NRTIs and either an INSTI or a bPI, with an available pre-ART resistance genotype. The endpoint was virological failure (VF; plasma HIV-1 RNA >200 copies/mL after week 24). WHO surveillance drug resistance mutations and the Stanford algorithm were used to classify patients into three resistance categories: no TDR (A), TDR but fully-active ART prescribed (B), TDR and at least low-level resistance to one or more prescribed drug (C). Results: We included 1365 patients with a median follow-up of 96 weeks (IQR 54-110): 1205 (88.3%) starting bPI and 160 (11.7%) INSTI. Prevalence of TDR was 6.1%, 12.5%, 2.6% and 0% for NRTI, NNRTI, bPI and INSTI, respectively. Cumulative Kaplan-Meier estimates for VF at 48 weeks were 11% (95% CI 10.1%-11.9%) for the bPI group and 7.7% (95% CI 5.4%-10%) for the INSTI group. In the INSTI group, cumulative estimates for VF at 48 weeks were 6% (95% CI 4%-8%) in resistance category A, 5% (95% CI 1%-10%) in B and 50% (95% CI 30%-70%) in C (P < 0.001). Resistance category C [versus A, adjusted hazard ratio (aHR) 12.6, 95% CI 3.2-49.8, P < 0.001] and nadir CD4 (+100 cells/mm3, aHR 0.6, 95% CI 0.4-0.9, P = 0.03) predicted VF. In the bPI group, VF rates were not influenced by baseline resistance. Conclusions: Our data support the need for NRTI resistance genotyping in patients starting an INSTI-based first-line ART.
Authors: Emily P Hyle; Justine A Scott; Paul E Sax; Lucia R I Millham; Caitlin M Dugdale; Milton C Weinstein; Kenneth A Freedberg; Rochelle P Walensky Journal: Clin Infect Dis Date: 2020-03-17 Impact factor: 9.079
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