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/mm(3), 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.

Spertilli Raffaelli, C., Rossetti, B., Paglicci, L., Colafigli, M., Punzi, G., Borghi, V., et al. (2018). Impact of transmitted HIV-1 drug resistance on the efficacy of first-line antiretroviral therapy with two nucleos(t)ide reverse transcriptase inhibitors plus an integrase inhibitor or a protease inhibitor. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 73(9), 2480-2484 [10.1093/jac/dky211].

Impact of transmitted HIV-1 drug resistance on the efficacy of first-line antiretroviral therapy with two nucleos(t)ide reverse transcriptase inhibitors plus an integrase inhibitor or a protease inhibitor

Spertilli Raffaelli C
;
Rossetti B;Paglicci L;Zazzi M;De Luca A;Zanelli G
2018-01-01

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/mm(3), 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.
2018
Spertilli Raffaelli, C., Rossetti, B., Paglicci, L., Colafigli, M., Punzi, G., Borghi, V., et al. (2018). Impact of transmitted HIV-1 drug resistance on the efficacy of first-line antiretroviral therapy with two nucleos(t)ide reverse transcriptase inhibitors plus an integrase inhibitor or a protease inhibitor. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 73(9), 2480-2484 [10.1093/jac/dky211].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1060031