Efficacy and safety of raltegravir plus etravirine and darunavir/ritonavir in treatment-experienced patients with multidrug-resistant virus: 48-week results from the ANRS 139 TRIO trial
Background: The week (wk) 24 primary analysis showed that the combination of raltegravir, etravirine and darunavir/r results in potent virologic efficacy in treatment-experienced patients. We present here efficacy and safety data at 48 weeks.
Methods: Phase II non-comparative multi-center trial that enrolled patients with viral load (VL)>1000 copies/ml, naïve to the investigational drugs, with a history of virologic failure while on NNRTI, with ≥3 primary PI and NRTI mutations and ≤3 darunavir and NNRTI mutations at screening. Backbone regimens included NRTI and/or enfuvirtide whenever possible. At wk48, failure was defined by: (i) VL < 50 copies/ml at wk24 or (ii) among those with VL < 50 copies/ml at wk24, VL < 50 copies/ml on two consecutive measures between wk24 and wk48.
Results: The trial included 103 patients. Baseline median VL was 4.2 log10 copies/ml, CD4 count 255 cells/mm3, median number of mutations was 4 for PIs, 2 for darunavir, 1 for NNRTIs and 6 for NRTIs.
The regimens included NRTIs in 86 (84%) and enfuvirtide in 12 patients (12%). At wk24, 93 patients (90%) had VL < 50 copies/ml among whom 4 patients experienced virological failure between wk24 and wk48. The proportion of patients with virologic success at wk48 was 86%, (89/103, 95%CI 80 to 93). Median CD4 increase at wk48 was 108 cells/mm3. Two patients presented a new AIDS-defining event (HIV encephalopathy, oesophageal candidiasis). One patient died due to a myocardial infarction syndrome after aortobifemoral bypass surgery.
Grade 3/4 clinical adverse events (AE) were reported in 15 patients (15%) (considered to be drug-related n=4, treatment discontinuation n=1). Grade 3/4 laboratory AE were reported in 20 patients (19%) (including CK n=11, GGT n=4, no treatment discontinuation).
Conclusion: Raltegravir, etravirine and darunavir/r combination was well tolerated and provided potent and durable virological suppression in patients with resistant viruses and limited treatment options.
C. Fagard1, D. Descamps2, V. Dubar3, C. Colin1, A.-M. Taburet4, B. Roquebert2, C. Katlama5, C. Jacomet6, C. Piketty7, J.-M. Molina8, G. Chene1, Y. Yazdanpanah3, ANRS 139 TRIO Trial Group
1INSERM U897, Bordeaux, France, 2Hosp Bichat-Claude Bernard, Paris, France, 3Hosp Tourcoing, Tourcoing, France, 4Hosp Bicetre, Le Kremlin Bicetre, France, 5Hosp Pitie-Salpetriere, Paris, France, 6Hosp Clermont-Ferrand, Clermont-Ferrand, France, 7Hosp Georges Pompidou, Paris, France, 8Hosp Saint Louis, Paris, France