NEW YORK (Reuters Health) – For initial treatment of HIV-1 infection, once daily atazanavir plus ritonavir and once-daily efavirenz provide comparable antiviral efficacy when used with either abacavir/lamivudine or tenofovir disoproxil fumarate (DF)/emtricitabine, according to research published today.

In the February 14 issue of Annals of Internal Medicine, Dr. Eric S. Daar of the Los Angeles Biomedical Research Institute at Harbor-ULCA Medical Center and colleagues point out that data comparing once-daily options for initial therapy of HIV-1 infection are “limited.”

They conducted a randomized equivalence trial in more than 1,800 antiretroviral therapy naïve HIV-1-infected patients. Eligible patients were randomly assigned in fairly equal numbers to open label atazanavir 300 mg plus ritonavir 100 mg or efavirenz 600 mg with placebo-controlled abacavir 600 mg/lamivudine 300 mg or tenofovir DF 300 mg/emtricitabine 200 mg. About 70% of patients in each arm completed follow-up.

“Primary efficacy was similar between atazanavir plus ritonavir and efavirenz with abacavir/lamivudine or tenofovir DF/emtricitabine,” they report, although they were unable to declare equivalence based upon pre-specified hazard ratio boundaries. This is likely the result of the low rate of virologic failure at 96 weeks (11% to 17%), rather than that projected (32%), the researchers say.

“Nevertheless, in a post-hoc assessment the difference in probability of remaining free of virologic failure at 96 weeks did not exceed the 10% to 12% threshold typically used for defining equivalence or non-inferiority,” the note.

They also note that in the high viral load stratum (HIV-1 RNA, 100,000 copies/mL or greater), those taking atazanavir/ritonavir with abacavir/lamivudine had a higher rate of failure compared to those taking efavirenz (hazard ratio, 1.68), a difference not seen in low viral load stratum (hazard ratio, 0.99).

There was a longer time to safety events (first grade 3/4 sign, symptoms or laboratory abnormality; P = 0.048) and tolerability events (change/discontinuation of regimen; P < 0.001) in those given atazanavir plus ritonavir than efavirenz with abacavir/lamivudine, but not with tenofovir DF/emtricitabine. Change in CD4 cells did not differ between those given atazanavir plus ritonavir or efavirenz with abacavir/lamivudine (P = 0.94 and 0.89, respectively). Change in CD4 cells was greater in those given atazanavir plus ritonavir compared to efavirenz with tenofovir DF/emtricitabine at weeks 48 and 96 (P = 0.40 and P = 0.002, respectively). There was no significant difference in time to AIDS or death in those assigned to atazanavir plus ritonavir versus efavirenz with abacavir/lamivudine (hazard ratio 0.93) or tenofovir DF/emtricitabine (hazard ratio 1.23). “Our analyses showed for the first time in a large randomized study that a ritonavir-boosted protease inhibitor had similar virologic efficacy to an efavirenz-based regimen with either abacavir/lamivudine or tenofovir DF/emtricitabine,” the investigators note. “There were, however, differences between regimens in CD4 cell increases, frequency of emergent resistance, rates of safety and tolerability events and changes in fasting lipid and renal parameters. These factors should be considered when selecting initial treatment for patients with HIV-1 infection,” they conclude. They point out that rates of safety and tolerability endpoints were lower among those assigned to atazanavir plus ritonavir than efavirenz with abacavir/lamivudine, with no differences when combined with tenofovir DF/emtricitabine. The fact that resistance testing prior to the start of treatment was not uniformly performed and routine HLA-B*5701 testing prior to use of abacavir was not routine at the time of enrollment are two limitations of the study, the researchers say. Overall, however, they say the results of this study “provide useful information for clinicians and patients making decisions regarding the initial treatment of HIV-1 infection.” The study was funded by the National Institutes of Health. Abbott Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline provided the study medications. A complete of author disclosures can be found with the original article. Ann Intern Med 2011.