Paper # 549|
Long-term Follow-up of Patients Receiving RAL, ETV, and DRV/r in the ANRS 139 TRIO Trial
Catherine Fagard*1, D Descamps2, C Colin1, A-M Taburet3, J-M Molina4, C Katlama5, F Raffi6, F Jeanblanc7, G ChÍne1, Y Yazdanpanah8, and ANRS 139 TRIO Trial Group
1INSERM U897, Bordeaux, France; 2Hosp Bichat Claude Bernard, Paris, France; 3Hosp BicÍtre, Paris, France; 4Hosp St Louis, Paris, France; 5Hosp Pitie-Salpetriere, Paris, France; 6Hosp HŰtel Dieu, Nantes, France; 7Hosp Edouard Herriot, Lyon, France; and 8Hosp Tourcoing, France
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
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