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Atazanavir intracellular concentrations remain stable during pregnancy in HIV-infected patients.
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2017 Nov 01; Vol. 72 (11), pp. 3163-3166. - Publication Year :
- 2017
-
Abstract
- Background: Atazanavir (300 mg) boosted by ritonavir (100 mg) is the preferred third drug in pregnancy. However, there is still discordance on atazanavir dose increase during the third trimester.<br />Objectives: To evaluate plasma and intracellular atazanavir and ritonavir concentrations in HIV-infected women during pregnancy and after delivery.<br />Methods: This was an observational study. HIV-infected pregnant patients treated with atazanavir/ritonavir plus either tenofovir/emtricitabine or abacavir/lamivudine had been prospectively enrolled after having signed a written informed consent form. Plasma and intracellular atazanavir and ritonavir Ctrough (24 ± 3 h after drug intake) were measured at each visit during the first, second and third trimesters and post-partum using validated HPLC-MS and HPLC-photodiode array methods (with direct evaluation of cellular volume). Data are described as median (IQR) and compared through non-parametric tests.<br />Results: Twenty-five patients were enrolled; at baseline, the median age was 32 years (27-35). All patients had plasma HIV RNA <50 copies/mL; the median CD4+ count was 736 cells/mm3 (542-779). Atazanavir plasma concentrations were 441 ng/mL (261-1557), 710 ng/mL (338-1085), 556 ng/mL (334-1022) and 837 ng/mL (608-1757) during the first, second and third trimesters and post-partum, respectively; intracellular concentrations were 743 ng/mL (610-1928), 808 ng/mL (569-1620), 756 ng/mL (384-1074) and 706 ng/mL (467-2688), respectively. Atazanavir intracellular/plasma ratios were 1.32 (0.98-2.77), 1.34 (1.13-1.88), 1.38 (0.61-2.63) and 1.07 (0.56-2.69), respectively. Atazanavir intracellular concentrations and intracellular/plasma ratios showed non-significant changes over time (P > 0.05).<br />Conclusions: This is the first demonstration that intracellular atazanavir exposure remains unchanged during pregnancy supporting the standard 300/100 mg atazanavir/ritonavir dosing throughout pregnancy.<br /> (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adult
Atazanavir Sulfate adverse effects
Atazanavir Sulfate therapeutic use
CD4 Lymphocyte Count
Chromatography, High Pressure Liquid
Drug Therapy, Combination
Emtricitabine therapeutic use
Female
HIV Infections metabolism
HIV Infections virology
HIV Protease Inhibitors blood
HIV Protease Inhibitors therapeutic use
HIV-1 drug effects
Humans
Infant, Newborn
Leukocytes, Mononuclear chemistry
Pregnancy
Pregnancy Complications, Infectious metabolism
Pregnancy Complications, Infectious virology
Pregnancy Trimesters metabolism
Prospective Studies
RNA, Viral blood
Ritonavir administration & dosage
Ritonavir therapeutic use
Tenofovir therapeutic use
Viral Load
Atazanavir Sulfate administration & dosage
Atazanavir Sulfate pharmacokinetics
HIV Infections drug therapy
HIV Protease Inhibitors administration & dosage
HIV Protease Inhibitors pharmacokinetics
Pregnancy Complications, Infectious drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 72
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 28961777
- Full Text :
- https://doi.org/10.1093/jac/dkx274