Different effects of the companion antiretroviral drugs on dolutegravir trough concentrations.

Autor: Cattaneo D; Department of Infectious Diseases.; Gestione Ambulatoriale Politerapie (GAP) Outpatient Clinic, ASST Fatebenefratelli Sacco University Hospital, Milan, Italy., Pagano S; Department of Infectious Diseases., Colombo ML; Department of Infectious Diseases., Giacomelli A; Department of Infectious Diseases., Gori A; Department of Infectious Diseases., Gervasoni C; Department of Infectious Diseases.; Gestione Ambulatoriale Politerapie (GAP) Outpatient Clinic, ASST Fatebenefratelli Sacco University Hospital, Milan, Italy.
Jazyk: angličtina
Zdroj: AIDS (London, England) [AIDS] 2024 May 01; Vol. 38 (6), pp. 847-851. Date of Electronic Publication: 2024 Jan 15.
DOI: 10.1097/QAD.0000000000003843
Abstrakt: Background: Dolutegravir is widely used in different dual and triple antiretroviral regimens. Here, we sought to investigate the effect of the companion antiretroviral drug(s) on dolutegravir plasma trough concentrations in persons with HIV, with a focus on dual regimens.
Methods: Dolutegravir concentrations collected from October 2015 to March 2023 ( n  = 900) were stratified according to the main antiretroviral classes (NRTIs, NNRTIs, protease inhibitors) and according to single drugs. Dolutegravir concentrations measured in persons with HIV concomitantly treated with lamivudine were considered as the reference group.
Results: Dolutegravir trough concentrations were significantly higher in persons with HIV given protease inhibitors compared with the reference [1886 (1036-2940) versus 1575 (1026-2226) ng/ml; P  = 0.004]. The highest dolutegravir concentrations were measured in persons with HIV concomitantly treated with unboosted atazanavir [2908 (2130-4135) ng/ml]. Conversely, co-administration of darunavir/ritonavir resulted in significantly lower dolutegravir exposure [909 (496-1397) ng/ml; P  = 0.002 versus reference]. Among NNRTIs, the higher dolutegravir concentrations were measured in presence of rilpivirine [2252 (1489-2686); P  < 0.001 versus reference].
Conclusion: Dolutegravir trough concentrations are differently affected by individual antiretroviral drugs, with some drug combinations (i.e. dolutegravir/darunavir/cobicistat, or dolutegravir/rilpivirine) providing significantly higher than expected dolutegravir exposure. Such combinations might be advantageous when there are concerns about dolutegravir plasma exposure or resistance.
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Databáze: MEDLINE
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