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High rate of virologic success with raltegravir plus etravirine and darunavir/ritonavir in treatment-experienced patients with multidrug-resistant virus: results of the ANRS 139 TRIO trial
Presented by Yazdan Yazdanpanah, France.
Y. Yazdanpanah1, C. Fagard2, D. Descamps3, A.M. Taburet4, B. Roquebert3, I. Tschope2, C. Katlama5, G. Pialoux6, C. Jacomet7, C. Piketty8, D. Bollens9, J.-M. Molina10, G. Chene2
1Tourcoing Hospital, Tourcoing, France, 2INSERM U897, Bordeaux, France, 3Bichat-Claude Bernard Hosp, Paris, France, 4Kremlin Bicetre Hosp, Paris, France, 5Pitie-Salpetriere Hosp, Paris, France, 6Tenon Hosp, Paris, France, 7Clermont-Ferrand Hosp, Clermont-Ferrand, France, 8Georges Pompidou Hosp, Paris, France, 9Saint-Antoine Hosp, Paris, France, 10Saint-Louis Hosp, Paris, France
Objective: To assess the safety and efficacy of an antiretroviral regimen containing raltegravir, etravirine and darunavir/ritonavir in treatment-experienced HIV-1 infected patients with multidrug-resistant virus.
Methods: This phase II non-comparative multi-centered trial enrolled treatment-experienced HIV-1 infected patients with plasma viral load (VL) >1000 copies/ml who were naïve to the investigational drugs, had a history of virologic failure while on non-nucleoside reverse transcriptase inhibitors (NNRTI) and had ³3 primary protease inhibitor (PI) mutations, ³3 NRTI mutations and £3 darunavir and NNRTI mutations, documented by a genotypic resistance test at initial screening. Backbone regimens included NRTI and/or enfuvirtide whenever possible. The primary endpoint was the proportion of patients with undetectable VL (defined as VL <50 copies/ml) at week 24.
Results: The trial included 103 patients from 04/2007 to 08/2007. Among these patients, the median time since starting HIV treatment was 13 years, and 44% had a history of AIDS-defining events. Baseline median VL was 4 log10 copies/ml and baseline CD4 count was 255 cells/mm3 (nadir: 79 cells/mm3). Median number of mutations was 4 for PIs (primary mutations), 2 for darunavir, 1 for NNRTIs and 6 for NRTIs. The regimens of 83% of patients included NRTIs (with a median genotypic sensitivity score=0.5). Fourteen patients had enfuvirtide as part of their regimen (12 were enfuvirtide-naïve). Fifty-seven patients (55%) had undetectable VL at week 4 and 91 patients (88%) had undetectable VL at week 12. At week 24, 93 patients (90%; 95%CI: 85 to 96) had VL <50 copies/ml and 98 patients (95%) had VL <400 copies/ml. Median CD4 increase was +99 cells/mm3. Only one patient discontinued the investigational ARV regimen (after a skin rash).
Conclusions: In patients with resistant viruses and few remaining treatment options, the combination of raltegravir, etravirine and darunavir/r is safe and has a rate of virological suppression similar to that reported for treatment-naive patients.
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