Today at the 17th International AIDS Conference in Mexico City, Haubrich, et al, Di Perri, et al, and P. Cahn, et al presented posters with additional data from the DUET trials (which compare the NNRTI etravirine (TMC125) with placebo in people starting a salvage regimen containing ritonavir-boosted darunavir).
Because the number of new/active agents needed to optimally suppress HIV in treatment-experienced patients is not known, a subgroup analysis presented by Haubrich, et al (poster TUPE0048) sought to determine the response rates to darunavir/etravirine based on baseline genotypic and phenotypic scores in order to guide decisions about the number of new agents to use in a regimen.
DUET 1 and DUET 2 included approximately 600 triple-class experienced patients on stable (yet failing) therapy with viral load greater than 5000 copies/mL. Using darunavir plus optimized background therapy, patients were randomised to receive either etravirine (200mg twice daily) or placebo.
This subgroup analysis excluded those that used enfuvirtide (ENF) as a new drug, and excluded discontinuations for non-virologic failure. Previously described resistance-associated mutations (RAMs) to etravirine (ETR) or darunavir (DRV) and phenotype (Antivirogram) were analyzed for their ability to predict a confirmed HIV-1 RNA less than 50 copies at 24 weeks.
The results showed a decline in response rates with increasing numbers of combined DRV and ETR mutations. High response rates (78% less than 50) were seen in patients with zero combined total RAMs, and there was 0% response when there were a total of three ETR and three DRV RAMs present.
Virologic response rates within the range of those seen in naïve studies (greater than 65%) were seen when the total number of ETR and DRV RAMS was less than or equal to three, and are also seen when the FC DRV was less than or equal to 40, and the FC to ETR was less than or equal to three.
The authors conclude that while high responses are also seen in patients with more resistance, these patients might benefit from additional active agents.
A poster by Di Perri, et al (poster TUPE0061) looked at the impact of the background regimen on virologic response to etravirine, as determined by the phenotypic sensitivity score (PSS). They determined that while the proportion of responders in both the ETR and placebo arm increased with increasing numbers of sensitive ARVs in the background regimen, superior virologic responses were seen with ETR versus placebo irrespective of PSS, ENF use, DRV FC and NRTI sensitivity, and baseline DRV RAMs.
An additional poster by P. Cahn et al assessed the impact of baseline characteristics on virologic response to etravirine. They found that patients in the ETR group consistently achieved higher response rates than those in the placebo group irrespective of ENF use, race, disease characteristics, or previous NNRTI use. They also found that while baseline viral load, CD4+ cell count, ENF use, and number of sensitive background agents were predictors of response in both groups, ETR provided added benefit in each subgroup.
08/06/08
DUET Study Updates
Source: Reporting from Mexico City for PRN News: Anita Radix MD, MPH and Rona Vail MD