Atazanavir intracellular concentrations remain stable during pregnancy in HIV-infected patients

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. Objectives: To evaluate plasma and intracellular atazanavir and ritonavir concentrations in HIV-infected women during pregnancy and after delivery. 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) weremeasured at each visit during the first, second and third trimesters and post-partumusing validated HPLCMS and HPLC-photodiode array methods (with direct evaluation of cellular volume). Data are described as median (IQR) and compared through non-parametric tests. 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). Conclusions: This is the first demonstration that intracellular atazanavir exposure remains unchanged during pregnancy supporting the standard 300/100mg atazanavir/ritonavir dosing throughout pregnancy.