ABSTRACT
UNLABELLED: Etravirine (ETV) is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A) subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) switched due to adverse events and group B) subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to <50 copies/mL after 24 weeks on treatment, or a confirmed viral load >200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9-92.1%) and 77.4% (CI95, 65.0-89.7%), respectively; the rates reached 97.2% (CI95, 95.1-99.3%) and 90.5% (CI95, 81.7-99.3), by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1-2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily) plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT01437241.
Subject(s)
Gene Expression Regulation, Viral/drug effects , HIV Infections/drug therapy , Pyridazines/pharmacology , Reverse Transcriptase Inhibitors/pharmacology , Salvage Therapy/methods , Drug Therapy, Combination , Endpoint Determination , Humans , Kaplan-Meier Estimate , Nitriles , Pyridazines/adverse effects , Pyridazines/therapeutic use , Pyrimidines , RNA, Viral/metabolism , Reverse Transcriptase Inhibitors/adverse effects , Reverse Transcriptase Inhibitors/therapeutic use , Spain , Treatment OutcomeABSTRACT
Efficacy and tolerability of telaprevir, pegylated interferon and ribavirin combination was assessed in 32 cirrhotic genotype 1 hepatitis C (HCV)-HIV coinfected patients. Undetectability of HCV-RNA was observed in 23/32 (71.9%) patients after 24 weeks. Treatment failure was observed in 9/32 subjects: four of them (45.5%) failed triple therapy due to virological rebound, while 5 patients (55.5%) experienced drug-related side effects driving to treatment interruption. These data suggest that telaprevir-containing triple therapy should be considered for treatment of genotype 1 HCV in HIV coinfected patients with liver cirrhosis, although a close vigilance is required because of potential drug-related side effects.
