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Switch to once or twice daily unboosted atazanavir in a cohort of stable HIV patients: strong differences in drug exposure and virological outcome

Purpose of the study

Switch to once daily unboosted (u) atazanavir (ATV) is an attractive option for HIV-infected patients with undetectable viral load, due to its convenience and favorable metabolic profile. However, due to a large interindividual variability, increased risk of inadequate ATV plasma concentrations (ATVc) and virological failure (VF) may be observed. Dividing the daily dose in a twice a day (BID) regimen could increase ATVc and improve virological success.

Methods

In a prospective observational cohort of HIV-infected patients, all individuals with undetectable viral load who were switched to uATV during at least one month were retrospectively selected. ATVc were measured by a validated HPLC in all patients at least two weeks after the initiation of ATV. ATVc was considered inadequate when trough concentration was below 0,150 mg/L. Patients with once (400 mg QD) versus twice daily (200 mg BID) uATV were compared.

Summary of results

From 2002 to 2009, 58 patients who received a total of 69 uATV based-regimens (27 QD and 42 BID regimens) were included. At the start of uATV, patients received a median duration of 9 years (IQR 4-11) of antiretroviral therapy. The mean exposure time of uATV was 16 months. Clinical characteristics and comedications (including tenofovir) were similar in the two groups. ATVc was inadequate in 17 (63%) patients in the QD group versus 4 (9%) patients in the BID group (p<0.001). During the follow up, VF happened significantly more frequently in the QD group than in the BID group (6 [22%] versus 1 [2%]; p=0.012). VF or low ATVc lead to treatment discontinuation in10 (37%) QD regimens versus 4 (9%) BID regimens (p=0,06). No other significant differences were detected in the two groups.

Conclusions

Despite possible bias due to the observational study design, strong differences were detected in plasma drug exposure and virological outcome in our study. When a switch to uATV is proposed in HIV-controlled patients, BID would be preferred to QD.

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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Baudry, T., Boibieux, A., Gagnieu, M. et al. Switch to once or twice daily unboosted atazanavir in a cohort of stable HIV patients: strong differences in drug exposure and virological outcome. JIAS 13, P47 (2010). https://doi.org/10.1186/1758-2652-13-S4-P47

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  • DOI: https://doi.org/10.1186/1758-2652-13-S4-P47

Keywords

  • Drug Exposure
  • Tenofovir
  • Trough Concentration
  • Atazanavir
  • Virological Failure