Atazanavir in treatment naive patients, with and without ritonavir boosting

Although there are limited data on using atazanavir (ATZ), with or without ritonavir (RTV), in first line therapy, it is already widely used by some clinicians where once-daily regimens are important but where there is a caution against or intolerance to efavirenz.

Malan and colleagues from Port Elizabeth, South Africa, reported 48-week results from a 96-week study of 199 treatment-naive patients randomised 1:1 to receive either 300mg ATZ/100mg RTV or 400mg ATZ, in combination with 3TC and d4T-ER (the extended release formulation of d4T that is no longer in development). Mean baseline CD4 count and viral load was 235 cells/mm³ and 4.95 log copies/mL respectively.

At 48 weeks, by intent-to-treat analysis, 75% and 70% of the patients in the RTV-boosted and unboosted arms respectively, had viral load reduced to <50 copies/mL, (difference, 5.0; 95% CI 7.0, 17.0). CD4 increases were +189 and +224 cells/mm³ (difference -21.1; 95% CI -48.9, 6.6).

12% and 10% of patients discontinued before week 48 in the RTV and unboosted arms, and although similar rates of drug-related adverse events of at least moderate intensity were comparable between arms, adverse events-related discontinuations occurred more commonly in the ATV/r arm (8%) than the ATV arm (1%).

Persistent hyperbilirubinemia. jaundice and scleral icterus (all grades) were more common in the ritonavir-boosted ATZ/r arm (22%; 23%) than the ATV arm (7%; 13%).

At baseline, mean total cholesterol was 161 mg/dL and mean triglycerides was 145 mg/dL. Total cholesterol increased by a mean 15% for the ATV/r arm vs 6% for the ATV arm (p <0.01); mean increase in triglycerides was 26% for ATV/r vs 3% for ATV (p <0.01); a shift of NCEP triglyceride category occurred in 16% for ATV/r vs 11% for ATV.

Comment

This study is underpowered to answer the question of non-inferiority of unboosted ATV compared to ATV/r. Boosted ATV/r looses a substantial part of its potentially beneficial lipid friendly properties. No data on the relevant issue of the development of resistance to ATV was shown.

Atazanavir, boosted by ritonavir, only received approval for second-line indication in Europe. In the US atazanavir, boosted by ritnonavir, is approved for use in treatment naive and treatment experienced patients.

NOTE (added 2007): a paper in JAIDS reported a high rate of virological failure in a Swedish study of atazanavir/r monotherapy that resulted in early termination of the study. [2]