Switch to twice-daily unboosted atazanavir outdoes switch to once-daily dose

Retrospective analysis of French patients who switched from a suppressive regimen to once- or twice-daily unboosted atazanavir found higher atazanavir concentrations and better virologic responses in the twice-daily group.

The analysis involved 69 people with an undetectable viral load who switched to once- or twice-daily unboosted atazanavir from 2004 through 2009. Everyone had atazanavir concentrations measured at least 2 weeks after the switch and relevant clinical and virologic data. The investigators considered a trough concentration below 0.150 mg/L inadequate. Twenty-seven people took the protease inhibitor (PI) at a dose of 400 mg once daily and 42 took a twice-daily dose of 200 mg.

The once-daily and twice-daily groups did not differ significantly in age (average 48 and 50), proportion of men (63% and 79%), proportion with European origin (78% and 81%), time since HIV diagnosis (average 11 years in both groups), time on antiretroviral therapy (average 8 and 9 years), proportion starting a new two-nucleoside backbone (93% and 100%), number of previous PIs (average 2 in both groups), proportion switching from boosted atazanavir (44% and 31%), proportion taking tenofovir (52% and 31%, p=0.083), or baseline CD4 count (average 527 and 589).

Treatment duration averaged 18 months in the once-daily group and 14 months in the twice-daily group. Time to atazanavir level measurement was statistically equivalent in the two groups (average 7.8 weeks and 3.1 weeks, p=0.226). People who switched to a once-a-day dose gained more CD4 cells on average than the twice-a-day group, but this difference lacked statistical significance (41 versus 8, p=0.627).

Six out of 27 people (22%) who switched to once-daily atazanavir had a virologic failure during follow-up, compared with 1 of 42 (2%) in the twice-daily group, a significant difference (p=0.012). Seventeen people (63%) in the once-daily group versus 4 (9%) in the twice-daily group had an atazanavir trough below 0.150 mg/L (p<0.001). Average trough concentration was significantly lower with once-daily dosing (0.19 versus 0.36 mg/L, p=0.012). And significantly more people stopped once-daily atazanavir because of virologic failure or a low trough (10 [37%] versus 4 [9%], p=0.006). Three people in
both groups (11% and 7%) changed drugs because of intolerance (p=0.437). The only person with virologic failure while taking twice-daily atazanavir had a trough above 0.15 mg/L.

The investigators concluded that switching to twice-daily unboosted atazanavir may be more appropriate than switching to once-daily unboosted atazanavir in people with an undetectable viral load. They called for a randomised trial to validate their findings.

Baudry T et al. Switch to once or twice daily unboosted atazanavir in a cohort of stable HIV patients: strong differences in drug exposure and virological outcomes. 10th International Congress on Drug Therapy in HIV Infection. 711 November 2010. Glasgow. Abstract P047. Published in Journal of the International AIDS Society 2010, 13(Suppl 4):P47. doi:10.1186/1758-2652-13-S4-P47. http://www.jiasociety.org/content/13/S4/P47