Isentress Tablet

Intelence Tablet

Prezista Tablet

In the TRIO trial, French researchers assessed the safety and efficacy of an antiretroviral regimen containing the integrase inhibitor raltegravir (Isentress), the NNRTI etravirine (Intelence) and the ritonavir-boosted protease inhibitor darunavir (Prezista) in treatment-experienced HIV patients with multidrug-resistant virus. Yazdan Yazdanpanah reported their findings at the XVII International AIDS Conference last week in Mexico City.

This Phase II multicenter trial enrolled 103 treatment-experienced patients between April and August 2007. Most (88%) were men. Participants had plasma viral load > 1000 copies/mL, had not previously used the drugs under investigation, had a history of virological failure while on non-nucleoside reverse transcriptase inhibitors (NNRTIs), and had multiple HIV mutations conferring resistance to multiple drug classes.

At baseline, the median viral load was 4 log10 copies/mL and the median CD4 count was 255 cells/mm3 (nadir 79 cells/mm3). The median time since starting HIV treatment was 13 years, and 44% had a history of AIDS-defining events. Participants had a median of 4 primary protease inhibitor (PI) resistance mutations, 6 NRTI resistance mutations, and 1 NNRTI resistance mutation. Almost all (96%) had 1-3 darunavir resistance mutations and 65% had 1-3 etravirine resistance mutations.

Backbone regimens included NRTIs and the injectible entry inhibitor enfuvirtide (T-20; Fuzeon) whenever possible. The regimens of 83% of patients included NRTIs (with a median genotypic sensitivity score=0.5); 14 included enfuvirtide as part of their regimen, of whom 12 were enfuvirtide-naive).

The primary endpoint was the proportion of patients with undetectable viral load (< 50 copies/mL) at week 24.

Results

• 57 patients (55%) had undetectable viral load at week 4.

• 91 patients (88%) had undetectable viral load at week 12.

• At week 24, 93 patients (90%) had viral load < 50 copies/mL and 98 (95%) had viral load < 400 copies/mL.

• The mean reduction in HIV RNA was 2.4 log10.

• The median CD4 cell increase was 99 cells/mm3.

• Regimens containing the 3 study drugs were generally well tolerated.

• 5 patients experienced significantly elevated creatinine levels.

• Only 1 patient discontinued the investigational regimen (after a skin rash).

These findings show the potentially significant advantages of using 3 fully active oral drugs in treatment-experienced patients with multidrug-resistant HIV. The study is continuing through 48 weeks.

Based on the results of their study, the investigators concluded, "In patients with resistant viruses and few remaining treatment options, the combination of raltegravir, etravirine and darunavir/ritonavir is safe and has a rate of virological suppression similar to that reported for treatment-naive patients."

Tourcoing Hospital, Tourcoing, France; Bichat-Claude Bernard Hosp, Paris, France; Kremlin Bicetre Hosp, Paris, France; Pitie-Salpetriere Hosp, Paris, France; Tenon Hosp, Paris, France; Clermont-Ferrand Hosp, Clermont-Ferrand, France; Georges Pompidou Hosp, Paris, France; Saint-Antoine Hosp, Paris, France; Saint-Louis Hosp, Paris, France.

8/15/08

Reference
Y Yazdanpanah, C Fagard, D Descamps, and others. 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. XVII International AIDS Conference (AIDS 2008). August 3-8, 2008. Mexico City. Abstract THAB0406.