Atazanavir (Reyataz) boosted by ritonavir (Norvir) has a potent anti-HIV effect and is generally well tolerated when used to treat individuals who have never taken anti-HIV therapy before, according to study presented to the Thirteenth Conference on Retroviruses and Opportunistic Infections in Denver on February 7th.
Boosted atazanavir is now widely prescribed in combination with other antiretrovirals to individuals who have been previously treated with one or more anti-HIV treatment regimen. At the moment, atazanavir/ritonavir is not recommended for first-line treatment because of a lack of safety and efficacy data.
In the open-label study AI424-089, researchers randomly assigned 200 HIV-positive, treatment-naive participants (199 of whom started treated) to receive either 300mg atazanavir boosted with 100mg ritonavir once daily, or else 400mg unboosted atazanavir once daily. All patients also received once-daily 3TC (lamivudine, Epivir) and extended-release d4T (stavudine, Zerit PRC). The study is scheduled to continue through 96 weeks.
Baseline characteristics were similar in both arms. The mean baseline CD4 cell count was 235 cells/mm3 and the mean HIV viral load was 4.95 log copies/ml. Mean total cholesterol and triglyceride levels were 161 mg/dL and 145 mg/dL, respectively.
After 48 weeks of therapy, using an intent-to-treat analysis, similar proportions of patients achieved undetectable viral load. In the boosted atazanavir arm, 86% of participants had viral loads below 400 copies/ml and 75% had HIV RNA below 50 copies/ml. In the unboosted atazanavir arm, the corresponding percentages were 85% and 70%. Using an as-treated analysis, 93% and 87% achieved viral loads below 400 copies/ml and below 50 copies/ml, respectively, in the boosted atazanavir arm, compared with 93% and 76%, respectively, in the unboosted arm.
The researchers calculated a comparative “difference estimate” of 1.5 (95% confidence interval [CI] 8.2-11.1) for viral load below 400 copies/ml and 5.0 (95% CI 7.0-17.0) for viral load below 50 copies/lL based on the intent-to-treat analysis. The corresponding estimates using the as-treated analysis were 0.2 (95% CI 7.4-7.8) and 11.2 (95% CI 0.2-22.6).
Increase in CD4 cell count was comparable between the two arms of the study, with patients taking atazanavir/ritonavir experiencing a mean increase of 189 cells/mm3 from baseline compared to 224 cells/mm3 amongst patients in the atazanavir arm.
When the investigators looked at safety data for the two arms of the study, they noted that a similar proportion of atazanavir/ritonavir (12%) and atazanavir (10%) recipients stopped treatment. However, more patients in the atazanavir/ritonavir arm stopped treatment because of side-effects (8%) than in the atazanavir arm (1%).
Hyperbilirubinaemia involving jaundice (22%) and yellowing of the eyes (23%) were more common in the ritonavir-boosted arm than the atazanavir arm (7% and 13%).
The investigators also noted that the mean increase in total cholesterol was significantly higher amongst patients taking atazanavir/ritonavir than those taking atazanavir (15% vs. 6%, p
Atazanavir, with or without ritonavir boosting has a high rate of virologic response in treatment-naïve patients, the investigators concluded. They stress the higher rate of hyperbilirubinaemia amongst patients taking the ritonavir- boosted version of the drug and call for further studies looking at the use of atazanavir/ritonavir in treatment-naïve individuals.
Malan N et al. Efficacy and safety of atazanavir-based therapy in antiretroviral naïve HIV-1 infected subjects, both with and without ritonavir: 48 week results from AI424-089. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 107LB, 2006.