No Efficacy Differences in ACTG Study Comparing Sustiva or Reyataz with either Epzicom or Truvada

February 19, 2010

Among HIV-positive patients with viral loads below 100,000 copies per milliliter (mL), there are no significant differences in long-terms effectiveness between those using Norvir (ritonavir)-boosted Reyataz (atazanavir) or Sustiva (efavirenz) in combination with either Epzicom (abacavir plus lamivudine) or Truvada (tenofovir plus emtricitabine), according to final results from a federally funded AIDS Clinical Trials Group (ACTG) study reported on Wednesday, February 17, at the 17th Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco. 

The results are encouraging in light of a preliminary analysis reported at the XVII International AIDS Conference (IAC) in 2008, indicating that people taking Epzicom experience virologic failure and moderate-to-severe side effects faster than those using Truvada. (An analysis of six clinical trials reported at the conference by ViiV Healthcare [then GlaxoSmithKline], Epzicom’s manufacturer, indicated similar safety and efficacy among patients with viral loads both above 100,000 copies.)

Background

ACTG study 5202 was a 96-week study that enrolled more than 1,800 people living with HIV who had never before taken antiretroviral (ARV) drugs. The study participants were split into four groups comparing the safety and efficacy of four popular ARV 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 Norvir-boosted Reyataz, a third started a regimen containing Truvada and Sustiva (now often used together as Atripla), and the last started a regimen containing Truvada and Norvir-boosted Reyataz. 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—both fixed-dose combinations of two nucleoside reverse transcriptase inhibitors (NRTIs)—were being used.

In February, a data and safety monitoring board (DSMB) overseeing the ACTG study recommended participants who began treatment with viral loads in excess of 100,000 copies be told which NRTI combination they were allotted to and provided with the option of switching to Truvada or an alternative NRTI regimen. Among those with viral loads below 100,000 copies/mL, however, the study continued as planned.

Approximately 83 percent of the study participants were male, 33 percent were black, and 23 percent were Hispanic. Pre-treatment viral loads averaged 50,000 copies and CD4 counts averaged 230 cells. 

Final Results

Taking the podium at CROI, ACTG 5202 study investigator Eric Daar, MD, of the Los Angeles Biomedical Research Institute at Harbor-UCLA explained that in the overall analysis of the study—involving all patients, regardless of their pre-treatment viral load—treatment was highly successful in all study groups, with no significant differences between them. 

Among those receiving Epzicom, 83 percent in the Reyataz group and 85 percent in the Sustiva group had viral laods below 50 copies/mL after 96 weeks. Among those receiving Truvada, 89 percent in the Reyataz group and 90 percent in the Sustiva group were still responding well to therapy after 96 weeks.

A little more than half of the entire study population had viral loads below 100,000 copies/mL before beginning treatment.

Among those receiving Norvir-boosted Reyataz with had pre-treatment viral loads below 100,000 copies/mL, there was no statistically significant difference between those also taking Epzicom and those taking Truvada. Eight-eight percent and 90 percent in these groups, respectively, had viral loads below 50 copies/mL after 96 weeks.

Among those receiving Sustiva with pre-treatment viral loads below 100,000 copies/mL, there was also no statistically significant difference between those taking Epzicom compared with those taking Truvada: 87 percent versus 89 percent, respectively, had viral loads below 50 copies/mL. 

When comparing Epzicom with Truvada, no significant differences were noted after 96 weeks among those with pre-treatment viral loads below 100,000 copies/mL. Among those receiving Epzicom, viral loads remained below 50 copies/mL for 96 weeks in 83 percent of those receiving Norvir-boosted Reyataz compared with 85 percent of those receiving Sustiva. Among those receiving Truvada, viral loads remained below 50 copies/mL in 89 percent of those taking Norvir-boosted Reyataz and 90 percent of those taking Sustiva.

CD4 count gains after 96 weeks were similar among those in the Reyataz groups and Sustiva groups. Among those taking Reyataz, CD4 counts increased by an average  of 221 cells when combined with Truvada and 251 cells when combined with Epzicom. Among those taking Sustiva, CD4 counts increased by an average of 252 cells when combined with Truvada and 250 cells when combined with Epzicom.

Major drug-resistance mutations associated with virologic failure were more likely to be found in those taking Sustiva compared Reyataz, regardless of whether Epzicom or Truvada were used. 

Moderate-to-severe adverse events occurred more quickly among those taking Sustiva combined with Epzicom compared with those taking Sustiva plus Truvada or Norvir-boosted Reyataz plus either Epzicom or Truvada. Similarly, the time to modify treatment, notably because of adverse events, was faster among those taking Epzicom compared with Truvada, regardless of which third drug was used. 

Most of the regimen changes were related to the hypersensitivity reaction (HSR), typically seen in about 5 percent of people using abacavir, though it is important to note that an assay to screen patients for possible HSR to abacavir has been made commercially available since ACTG 5202 first began enrolling patients in 2005.

Daar reported some differences in lipid levels observed during the study. Simply put, Sustiva was more likely to be associated with increases in total, “bad” LDL and “good” LDL cholesterol compared with Norvir-boosted Reyataz. Epzicom was more likely to be associated with increases in these lipids than Truvada.

In summarizing these data, Daar pointed out that because of the way the study was designed and the high degree of success in all treatment groups, it was not possible for the ACTG 5202 team to conclude that all regimens are, in fact, “equivalent.” However, Daar was able to say that, at least for those with pre-treatment viral loads below 100,000 copies/mL, the regimens “were not demonstrably different”—a positive outcome. 

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