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

C. Spertilli Raffaelli, B. Rossetti, L. Paglicci, M. Colafigli, G. Punzi, V. Borghi, M. Pecorari, M. M. Santoro, G. Penco, A. Antinori, M. Zazzi, A. De Luca, G. Zanelli

Research output: Contribution to journalArticle

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 firstline ART.

Original languageEnglish
Pages (from-to)2480-2484
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume73
Issue number9
DOIs
Publication statusPublished - Jan 1 2018

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

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