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  10th International Congress on Drug Therapy in HIV Infection
November 7-11, 2010
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Switch to Twice-Daily Unboosted Atazanavir Outdoes Switch to Once-Daily Dose
  Tenth International Congress on Drug Therapy in HIV Infection, November 7-11, 2010, Glasgow
Mark Mascolini
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 [1].
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 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 randomized trial to validate their findings.
1. Baudry T, Boibieux A, Gagnieu MC, 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. Tenth International Congress on Drug Therapy in HIV Infection. November 7-11, 2010. Glasgow. Abstract P047.