February 28, 2008
An independent Data and Safety Monitoring Board (DSMB) met recently to review data from a clinical trial examining the safety, tolerability and effectiveness of four different antiretroviral treatment regimens in HIV-infected adults who had never taken anti-HIV drugs before. The trial, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, involves a randomized comparison of the HIV drug efavirenz (EFV) with atazanavir boosted with ritonavir (ATV/r), and a double-blind, randomized comparison of co-formulations of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) with abacavir/lamivudine (ABC/3TC). The DSMB has recommended changes to the study on the basis of new findings in a subset of participants who have been receiving ABC/3TC.
This study is being conducted by the NIAID-funded AIDS Clinical Trials Group (ACTG) and is known as ACTG 5202. The trial is important for examining initial HIV treatment regimens because existing regimens may vary both in their ability to suppress the level of HIV in the blood (viral load) and in the side effects with which they may be associated.
Investigators enrolled 1,858 eligible men and women into the Phase III efficacy study between September 2005 and November 2007 at 64 sites in the United States. Participants were divided into two groups based on HIV levels at the time of screening: those with high viral loads (100,000 or more copies of HIV RNA per milliliter of blood) and those with lower viral loads (fewer than 100,000 copies/mL). Each volunteer was assigned at random to one of the four treatment groups:
All regimens effectively reduced the amount of virus in most participants. However, the DSMB found that among participants with high viral loads at the time of screening, treatment combinations that included ABC/3TC were not as effective in controlling the virus as those on regimens containing FTC/TDF. This was the DSMB's primary concern. Secondarily, the DSMB found that among participants with a high viral load at screening, those receiving ABC/3TC experienced a shorter time to developing non-specific side effects, such as body aches, and laboratory test abnormalities, such as elevated cholesterol and triglyceride levels, than those receiving FTC/TDF. In general, these side effects were obvious to participants or the study physicians and would have been readily managed or treated.
The DSMB had no safety concerns regarding EFV or ATV/r and recommended that study participants in the lower viral load group who were taking ABC/3TC should continue with their assigned treatment regimen.
Based on its findings, the DSMB recommended that all participants who had high viral loads at screening be told which treatment regimen they are receiving and stop taking their placebo pill. The DSMB also recommended that those participants receiving ABC/3TC who had high viral loads at screening be counseled on what the DSMB findings might mean for them and possibly be shifted to another regimen, if appropriate. Finally, the DSMB recommended that the remainder of the study continue as originally designed. NIAID concurred with the DSMB's recommendations.
ACTG has notified the site investigators and the affected study participants of the DSMB's recommendations. In consultation with the site study teams and their physicians, these participants may continue taking ABC/3TC, switch to FTC/TDF or switch to alternative antiretroviral combinations.