At the 17th International AIDS Conference in Mexico City Thursday, Paul Sax presented long-awaited data from the Phase-IIIB study concerning ACTG 5202 (abstract THAB0303). This double-blind study evaluates abacavir/lamivudine (ABC/3TC) vs tenofovir/emtricitabine (TFV/FTC) with open label efavirenz (EFV) or ritonavir-boosted atazanavir (ATZ/r), stratified by HIV RNA less or greater than 100,000 copies/mL (c/mL).
Primary study endpoints are time to first report of grade 3/4 adverse events (AE), and time to virologic failure (VF), defined as confirmed HIV RNA ≥1000 c/mL at 16-24 weeks or ≥200 c/mL at ≥24 weeks.
A planned Data Safety Monitoring Board (DSMB) review showed differences between the nucleoside arms in the strata ≥100,000 c/mL, which led to the unblinding of this arm; Sax presented results from this arm on Thursday.The results showed time to VF was significantly shorter in the ABC/3TC arm (HR 2.33, 95% CI 1.46-3.72, P=0.0003) occurring in 57 subjects vs 26 subjects in the TFV/FTC arm. While there were more virologic failures in the ABC/3TC group as compared to the TFV/FTC group, both arms did remarkably well with 86% and 94%, respectively, achieving a viral load of <50 c/mL in patients with a high baseline viral load.
There was also shorter time to Grade 3/4 AEs in the ABC/3TC arm, which was significant (HR 1.87, 95% CI 1.43-2.43, P<0.0001). Interestingly these were not due to abacavir hypersensitivity (HLA B5701 testing was not part of the protocol and the majority of patients had not been screened), as the number of suspected drug hypersensitivity reactions were the same in each arm (7%). Instead, the shorter time to Grade 3/4 AEs in the ABC/3TC arm were predominantly due to body aches and lipid increases, though Sax stated that he did not feel the lipid differences were clinically meaningful. It is not clear what role differences in adherence may have played in explaining the difference in efficacy given there were more AEs in the ABC/3TC arm.
Resistance data has not yet been analyzed, and the third agent in the regimen has not been unblinded. The rest of the study is ongoing with results not expected until 2010, so further data regarding resistance in virologic failures as well as comparing the efficacy of the 3rd agents in each arm are not expected until the rest of the study results are released.
In response to the DSMB unblinding of ACTG 5202, GlaxoSmithKline (GSK) conducted an analysis of other trials of ABC/3TC-containing regimens, and reviewed them using the efficacy endpoints defined in ACTG 5202 in order to assess the impact of baseline viral load on virologic response in other trials. Keith Pappa of GSK presented these results Thursday at the 17th International AIDS Conference in Mexico City (abstract THAB0304).
Six trials were analyzed in which 2940 subjects received ABC/3TC with a variety of third agents. They found no difference in time to VF and no differences in safety endpoints when stratifying by baseline viral load less than versus greater than or equal to 100,000 in their studies.
References:
Sax P, et al. ACTG 5202: Shorter time to virologic failure (VF) with abacavir/lamivudine (ABC/3TC) than tenofovir/emtracitabine (TDF/FTC) as part of combination therapy in treatment-naïve subjects with screening HIV RNA greater than or equal to 100,000 c/ml. Presented at: 17th International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract THAB0303.
Pappa K, et al. Abacavir/lamivudine (ABC/3TC) shows robust virologic responses in ART naïve patients for baseline (BL) viral loads (VL) of greater than or equal to 100,000 c/ml and less than or equal to 100,000 c/ml by endpoint used in ACTG 5202. Presented at: 17th International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract THAB0304.
08/07/08
Late Breaker Abstracts on Abacavir Differ on Efficacy at Greater Than 100,000 Copies/mL
Source: Reporting from Mexico City for PRN News: Anita Radix MD, MPH and Rona Vail MD