Background: The ANRS 139 TRIO trial showed a very high rate of virologic suppression in the short term in treatment-experienced HIV patients receiving a raltegravir-etravirine-darunavir/ritonavir regimen. We evaluated the sustainability of this regimen efficacy and its safety through week 96.

Methods:  TRIO was a phase II non-comparative trial that included 103 patients with multi-drug resistant HIV viruses. At week 48, patients were proposed to go through extended follow up until week 96 in order to evaluate long-term efficacy and safety. Follow-up visits were performed at weeks 60, 72, 84, and 96. Change in HIV RNA, failure defined by 2 consecutive measurements above 50 copies/mL, and CD4 are described as well as metabolic parameters.

Results:  One hundred patients were included in the extended follow up. Eighty-nine percent were male, median age was 45 years, 41% had a history of AIDS; median CD4 and HIV RNA at week 0 were 258 cells/mm³ and 4.2 log₁₀ copies/mL, respectively. None of the patients discontinued the study regimen between weeks 48 and 96 but 2 patients discontinued the trial follow up. Among the 82 patients treated with at least 1 nucleoside reverse transcriptase inhibitor (NRTI), only 2 discontinued NRTI. Despite low genotypic sensitivity score at baseline (median 0.5), fear of lost of efficacy was the main reason (74%) for pursuing NRTI. Five patients (5%) experienced virologic failure after week 48, all HIV RNA measurements were below 400 copies/mL, and in 4 of these HIV RNA decreased to less then 50 copies thereafter. In the 2 patients who discontinued trial follow up HIV RNA was <50 copies/mL at the last visit. At week 96, median CD4 was 384 cells/mm³ (IQR: 259 to 541) vs 360 cells/mm³ (IQR: 240 to 484) at week 48. Myocardial ischemia occurred in 3 patients (1 death). Five cases of cancer were reported (non Hodgkin lymphoma, Hodgkin lymphoma, anal carcinoma, myeloma, and recurrence of a Castelman disease). No severe renal or hepatic events were diagnosed. Median triglycerides were 2.5 mmol/L at week 0 and 2.2 at week 96. Median total cholesterol and HDL were respectively 5.3 and 1 mmol/L at weeks 0, 5.5 and 1.1 mmol/L at week 96. Glucose level remained stable at 5 and 5.1 mmol/L.

Conclusions:  Raltegravir, etravirine, and darunavir/r combination is highly efficacious and safe over at least 2 years of continuous treatment. None of the patients interrupted the study treatment after week 48. Virologic failure was rare and occurred at low-level viremia. Whether background therapy with NRTI can be safely discontinued in these patients would need a specific evaluation.