Source: Epilepsy Curr  |  Posted 5 years ago

By Ted Bosworth

BRIGHTON, UK -- April 4, 2006 -- Pooled data from 2 randomized studies and an open-label rollover study demonstrate that the investigational protease inhibitor (PI) TMC114 is highly effective for control of HIV infection in treatment-experienced patients.

When TMC114 is boosted with ritonavir (TMC114/r), the data show significant activity in patients with up to 4 PI mutations, the researchers reported.

"Virologic responses in the TMC114/r treatment group were consistently higher than for patients receiving comparator PIs at week 24, even when control patients were fully susceptible to their investigator-selected PIs," reported senior author Anton L. Pozniak, MD, consultant physician, Department of HIV and Genitourinary Medicine, Chelsea and Westminster Hospital, London, UK.

Providing these data at the 12[^]th[] Annual Conference of the British HIV Association (BHIVA), held here March 29 to April 1, 2006, Dr. Pozniak emphasized that "these data indicate TMC114/r provides a substantial reduction in viral load and an increase in CD4 counts in treatment-experienced HIV patients."

In this analysis, data were combined from 2 phase 2b studies, called the POWER 1 and 2 trials, as well as from the open-label rollover POWER 3 study. The combined data included 458 patients who received TMC114/r in a 600/100 twice-daily dose and 124 patients who received a comparator PI.

All patients were highly treatment experienced and had advanced HIV infection. At baseline, mean viral load was 4.6 log10 copies/mL and median CD4 count was 128 cells/mm[^]3[] The proportion of patients with 3 or more primary PI mutations was 73%.

At 24 weeks, the mean change in viral load on a regimen that included TMC 114/r was 1.74 log10 copies/mL versus 0.58 log10 copies/mL in patients who had at least 1 susceptible comparator PI (CPI) in their regimen. In those with no CPI in the regimen, the mean reduction in viral load was 0.43 log10 copies/mL. The proportions achieving a viral load of < 50 copies/mL in these 3 groups were 42%, 24%, and 7%, respectively.

In the analysis of predictors of response, the researchers found that for patients with baseline phenotypic TMC114 resistance levels less than 10-fold, the response was greatest for those with susceptible nucleoside reverse transcriptase inhibitors (NRTIs) or enfuvirtide (T-20) in the background treatment regimen. For those with phenotypic resistance levels greater than 10-fold, the additional efficacy benefits for using NRTIs and enfuvirtide in the background regimen was only marginal, Dr. Pozniak said. However, when enfuvirtide was assessed separately, the greatest benefit from the addition of this entry inhibitor was in those patients who were not receiving other antiretroviral agents for which HIV was predicted susceptible.

The results of the POWER analyses were said to be consistent with previously completed studies in highly treatment-experienced patients, such as RESIST I and II, which evaluated tipranavir, and TORO I and II, which evaluated T-20.

The benefit of TMC114/r increased when it could be paired with at least 1 other active agent, the researchers said. Although 26% of patients without any other susceptible antiretroviral agents in the background regimen did achieve a viral load of < 50 copies/mL at 24 weeks on TMC114/r, this rose to 46% in those with 1 additional agent to which infection was susceptible and to 49% when there were at least 2 agents to which HIV was predicted to be susceptible, Dr. Pozniak noted.

[Presentation title: Efficacy of TMC114/r in Treatment-Experienced HIV Patients: Factors Influencing Outcome in the Pooled 24-week Analysis of POWER 1, 2, and 3. Abstract P3]