August 15, 2006 (AIDSmeds)—Researchers at the XVI International AIDS Conference in Toronto have reported 48-week results from a phase II clinical trial of etravirine (TMC-125), Tibotec's experimental non-nucleoside reverse transcriptase inhibitor (NNRTI).The new data, reviewed by Cal Cohen, MD, of the Community ResearchInitiative of New England in Boston at a poster session on Tuesday,indicate that etravirine may offer long-term effectiveness to patientswho have tried and failed other HIV treatments, including currentlyapproved NNRTIs.

The study (TMC125-C223) enrolled 199 HIV-positive patients who had failed regimens containing NNRTIs and protease inhibitorsin the past. The study volunteers were randomized to one of twoetravirine doses (400mg or 800mg twice-daily) plus an "optimizedbackground regimen" (OBR) consisting of available HIV medications.These patients were compared to an "active control" group, in whichpatients cobbled together the best possible regimen using approved HIVmedications.

By week 48, approximately 39 of the 40(98%) patients in the active control group had discontinued theirselected treatment, mostly due to rebounding viral loads.In both etravirine groups, rebounds in viral load were only seen in 9%of the patients. Patients in the active control group remained on theirselected treatment regimen for an average of 18 weeks, compared to anaverage of time on therapy of 48 weeks in the etravirine groups.

Dr.Cohen's group also reported that 23% of patients in the 400mgetravirine group and 22% of patients in the 800mg etravirine group hadviral loads below 50 after 48 weeks of treatment, compared to nopatients in the active control group. Approximately 31% of patients inthe 400mg etravirine group and 34% of patients in the 800mg etravirinegroup had viral loads that were at least 1 log below their baselineresults, compared to only 8% in the active control group.

Patients with the fewest HIV mutations conferring resistanceto current NNRTIs – such as K103N and Y181C - had the most pronouncedreductions in viral load. For example, in the 800mg etravirine group,patients with only one NNRTI mutation saw their viral loads reduced by1.67 log by the end of the study, compared to a 0.54 log reduction inpatients with HIV containing three or more NNRTI mutations.

As for CD4 counts(T cell counts), there was a 61 cell increase in the 800mg etravirinegroup and a 58 cell increase in the 400mg group. In the active controlgroup, there was only a 13 cell increase.

Because mostpatients in the active control group discontinued their selectedtreatment relatively early in the trial, a true comparison of the sideeffects isn't really possible. Looking only at patients in theetravirine groups, approximately 22% experienced diarrhea, 20%experienced some type of rash, 20% experienced injection-site reactions(caused by administration of Fuzeon®),and 20% experienced fever. Other reported side effects, occurring ingreater that 10% of patients on an etravrine-containing combination,included fatigue, headache, and insomnia.

These data,Dr. Cohen reported, are encouraging. The results of etravirine's largerphase III clinical trials, which are being conducted to support theanticipated 2007 approval of the drug, are eagerly anticipated.