A data and safety monitoring board (DSMB) for the AIDS Clinical Trial Group (ACTG) has recommended changes to a large clinical trial comparing Epzicom (abacavir plus lamivudine) to Truvada (tenofovir plus emtricitabine) in combination with either Sustiva (efavirenz) or Norvir (ritonavir)-boosted Reyataz (atazanavir).
According to memos from organizers of ACTG study A5202 to researchers and patients participating in the clinical trial, patients receiving Epzicom who entered the study with high viral loads were somewhat less likely to achieve specific viral load milestones—and somewhat more likely to experience certain side effects—than those taking Truvada. Based on these interim DSMB findings, the memos dated February 22, 2008 recommend that patients who began the trial with viral loads in excess of 100,000 copies be told which nucleoside reverse transcriptase inhibitor combination they are receiving and be provided with the option of switching to Truvada or an alternative option.
A5202 is a 96-week study that, since its 2005 start date, has enrolled more than 1,600 people living with HIV who had never before taken antiretroviral drugs. The study participants were split into four groups to compare the safety and efficacy of four popular antiretroviral options among those starting therapy for the first time. One group started a regimen containing Epzicom and Sustiva, another started a regimen containing Epzicom and Reyataz/Norvir, a third started a regimen containing Truvada and Sustiva, and the last started a regimen containing Truvada and Reyataz/Norvir. Each of the four groups was further split into two groups depending on whether participants had viral loads under or over 100,000 copies.
The participants, as well as the study investigators, knew whether they were taking Sustiva or Reyataz/Norvir. The rest of their treatment regimen, however, was “blinded,” meaning that neither the investigators nor the participants knew whether Epzicom or Truvada were being used. This was accomplished by having those on Epzicom also take a placebo that looked like Truvada, and those on Truvada also taking a placebo that looked like Epzicom.
The DSMB notes that all regimens are effectively reducing viral loads in most participants. However, it also notes that the rates of virologic success differed among those who entered the study with viral loads over 100,000 copies, depending on whether they were receiving Epzicom or Truvada.
The overall number of people who failed to achieve virologic end points—in this case a viral load of less than 1,000 by week 16 and/or a viral load of less than 200 by week 24—was quite low. However, those with high pretreatment viral loads and taking Epzicom in the study were less likely to meet these end points than those taking Truvada. This difference was statistically significant, meaning that it was too great to have occurred by chance.
The DSMB also notes that rates of side effects have been low. However, people taking Epzicom were more likely to complain of body aches and to experience increases in cholesterol or triglycerides.
In their memos, the A5202 study team wrote, “As a result of the efficacy findings, the DSMB recommended that blinded follow-up of [Epzicom] in the subjects within the high viral load stratum be stopped. The DSMB stressed that their decision was based on the virologic efficacy findings in this stratum and that the safety differences were not the primary consideration for their recommendations.”
Participants who entered A502 with high viral loads will now learn whether they taking Epzicom or Truvada. They will also be given an option of continuing Epzicom, switching to Truvada or switching to alternative antiretroviral combinations.
The DSMB did not indicate any concerns regarding Sustiva or Reyataz/Norvir and, furthermore, is recommending that participants who entered the study with viral loads lower than 100,000 copies taking Epzicom continue their blinded treatment regimen.
It should be noted that several studies, including results presented at the 15th Conference on Retroviruses and Opportunistic Infections earlier this month, have not found a difference in effectiveness between Epzicom and Truvada.
The study investigators are encouraging A5202 participants who have questions or concerns to talk with their site study team. Other users of Epzicom who have questions about their treatment should contact their health care provider.