Atazanavir (Reyataz) with or without ritonavir boosting is safe and effective in treatment-naïve patients, according to latest long term data presented at the Fourth International AIDS Society Conference on HIV Treatment, Pathogenesis and Prevention in Sydney.
However, atazanavir boosted with ritonavir showed a trend towards a higher rate of viral suppression after 96 weeks, fewer virological rebounds and less protease inhibitor or nucleoside analogue resistance.
The results will give further support to the use of boosted atazanavir as part of a first potent antiretroviral regimen. Atazanavir is currently only recommended for use by treatment-experienced patients in the HIV treatment guidelines of the British HIV Association.
The AI424-089 trial was designed to compare atazanavir/ritonavir 300/100mg once daily with atazanavir 400mg once daily. Both groups also took once-daily lamivudine, (Epivir) plus extended release stavudine.
The average CD4 cell count in participants was around 200 cells/mm3 at baseline, and around half had viral load above 100,000 copies/ml at baseline.
Boosted atazanavir was not widely prescribed as part of combinations in treatment-naïve patients, due to lack of safety and efficacy data, until 48 week data from this trial were presented at CROI last year. In the United States atazanavir is already licensed for first-line prescription, with or without ritonavir boosting, but in Europe it is only licensed for use in treatment-experienced patients, boosted with ritonavir.
The 96 week data presented in Sydney show that patients taking either the boosted or unboosted regimen had rapid and potent suppression of HIV that was sustained throughout the 96 weeks of treatment.
However, response rates were slightly higher in those taking boosted atazanavir, with 65% of those achieving viral loads of less than 50 copies/ml compared to 55% of those taking the atazanavir alone by intent to treat analysis at week 96, although the authors say this difference was not statistically significant.
But there were fewer virologic failures among people taking atazanavir boosted by ritonavir (5 vs 16). Ten virological failures occurred between week 48 and week 96 in the unboosted group, compared with 2 in the boosted group. Protease inhibitor (5 cases vs 1) or NRTI substitutions were also more common in those taking unboosted atazanavir.
Five patients taking boosted atazanavir stopped treatment due to hyperbilirubinemia, compared to none of the unboosted group, and there was a much higher rate of grade 3/4 bilirubin elevations in the boosted atazanavir group (66% vs 24%).
Although more patients taking boosted atazanavir experienced lipid elevations during the study (20% vs 7% experienced total cholesterol increases), none reached cholesterol levels requiring intervention.
The investigators conclude that atazanavir - with our without ritonavir - taken once daily as part of an antiretroviral regimen is safe and effective in treatment-naïve HIV infected people, including those with advanced HIV disease.
Malan N et al. Efficacy and safety of atazanavir-based therapy in antiretroviral naïve HIV-1 infected subjects both with and without ritonavir: 96-week results from AI424-089. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, abstract WEPEB024, Sydney, 2007.