Boosted atazanavir approved in Europe as first-line therapy

On 24th June 2008, the European Commission granted marketing authorisation for atazanavir boosted by ritonavir (300mg/100mg once daily), in combination with other antiretrovirals, as a first-line treatment HIV-1 infected adults. [1]

Previously, atazanavir/r was only recommended in treatment-experienced patients.

This decision was based on results from the non-inferiority CASTLE study which randomised almost 900 naive patients to either once-daily atazanavir/r or twice-daily lopinavir/r with background tenofovir+FTC. Results were first presented at the Retrovirus conference in February and were reported in the March April issue of HTB. [2]

Efficacy was similar in both study arms; 78% vs 76% patients in the atazanavir/r and lopinavir/r arms respectively achieving viral load <50 copies/mL at week 48.

Safety events in the study were consistent with prior experience, and patients taking atazanavir/r experienced lower rates of Grade 2-4 adverse events such as diarrhoea (2%) and nausea (4%) than those taking lopinavir/r (11% and 8% respectively). Additionally, the atazanaivr/r arm was associated with significantly lower increases from baseline compared to the lopinavir/r arm in total cholesterol, triglycerides and non-HDL cholesterol at 48 weeks (all p<0.0001).

As with previous observation, 34% of the patients in the atazanaivr/r arm and less than 1% of patients in the twice-daily lopinavir/r arm experienced elevations in total bilirubin (hyperbilirubinaemia) greater than 2.5 times the upper limit of normal. This elevation was not associated with liver dysfunction as the rates of Grade 3-4 liver enzyme elevations were similar between treatment groups (2% in once-daily atazanaivr/r arm vs 1% in the twice-daily lopinavir/r arm).

Atazanavir 300mg boosted with 100mg ritonavir is now available in the UK for use in naive patients.

Comment

Many UK clinics were already using atazanavir/r as first line therapy as a once-daily PI option to efavirenz, and improved tolerability due to only requring 100mg dose of boosting ritonavir.

Atazanavir/r is now recommended as an alternative to efavirenz in the new BHIVA treatment guidelines (July 2008).