Tenofovir and efavirenz show promise as a two drug maintenance regimen

Michael Carter
Published: 26 July 2004

A maintenance regimen involving only two antiretroviral drugs appears to be just as good as a traditional three drug HAART regimen at controlling viral load and boosting CD4 cell count, according to interim data from a French study presented to the Fifteenth International AIDS Conference in Bangkok earlier this month.

Hopes that it might be possible to switch to a two drug maintenance regimen after suppression of viral load using early HAART regimens were dashed as viral load rapidly rebounded in individuals switching from three drug therapy to dual nucleoside analogue (NRTI) or single protease inhibitor maintenance regimens.

However, there is still a need for simpler, more tolerable anti-HIV treatment regimens, and French investigators wished to see if a two drug maintenance regimen using newer, more potent antiretrovirals was safe and effective.

Investigators designed a 48 week randomised, multicentre (the COOL Study) with plans to enroll 140 patients. Interim data for the first 45 individuals completing 24 weeks of follow-up were presented to the Bangkok conference.

The regimens assessed were maintenance therapy involving tenofovir and efavirenz versus a conventional three drug regimen of tenofovir, 3TC, and efavirenz.

To enter the trial patients had to have been taking a stable HAART regimen for at least three months, with a viral load below 50 copies/ml, and no history of treatment failure. There was no CD4 cell count entry criteria, but as tenofovir can cause abnormalities in kidney function, individuals were required to have creatinine clearance above 60ml/min.

Baseline characteristics were comparable across the two arms of the study. Patients had a mean age of 42 years, 23% were women and 80% were infected with HIV through sex. Just over a third of patients (36%) had an AIDS diagnosis, the median CD4 cell count was 496 and median viral load was 50 copies/ml. Before entering the study, 49.5% of patients had been taking a HAART regimen involving two NRTIs and a protease inhibitor, and 41% had been taking a non-nucleoside analogue (NNRTI) and two NRTIs.

By week 24, the median CD4 cell count had increased to 549 cells/mm3 across both arms of the study. A total of nine viral load “blips” above 50 copies/ml were observed. In all but one case viral load returned to below 50 copies/ml on retesting.

Only one treatment-related side-effect, dizziness associated with efavirenz, caused a patient to withdraw from the study.

The investigators conclude, “these preliminary results are very encouraging and allow continuing the COOL trial evaluation of tenofovir and efavirenz as dual therapy in HIV controlled patients.”

Reference

Girard PM et al. EFV/TDF vs EFV/3TC/TDF as maintenance regimen in virologically controlled patients under HAART: a 6-month analysis of the COOL trial. XV International AIDS Conference, Bangkok, abstract TuPeB4493, 2004.