Cerebrospinal fluid drug concentrations and viral suppression in HIV-1-infected patients receiving ritonavir-boosted atazanavir plus lamivudine dual antiretroviral therapy (Spanish HIV/AIDS Research Network, PreEC/RIS 39)



Imaz, Arkaitz, Niubo, Jordi, Amara, Alieu ORCID: 0000-0002-1137-2948, Khoo, Saye ORCID: 0000-0002-2769-0967, Ferrer, Elena, Tiraboschi, Juan M, Acerete, Laura, Garcia, Benito, Vila, Antonia and Podzamczer, Daniel
(2018) Cerebrospinal fluid drug concentrations and viral suppression in HIV-1-infected patients receiving ritonavir-boosted atazanavir plus lamivudine dual antiretroviral therapy (Spanish HIV/AIDS Research Network, PreEC/RIS 39). JOURNAL OF NEUROVIROLOGY, 24 (4). pp. 391-397.

[img] Text
NIJV-D-18-00001_Accepted version_AA.docx - Author Accepted Manuscript

Download (237kB)

Abstract

This study aimed to assess cerebrospinal fluid (CSF) drug concentrations and viral suppression in HIV-1-infected patients on ritonavir-boosted atazanavir (ATV/r) plus lamivudine (3TC) dual therapy. HIV-1-infected adults with suppressed plasma HIV-1 RNA who switched to ATV/r plus 3TC were studied. Total ATV and 3TC concentrations at the end of the dosing interval (C<sub>24h</sub>), using a validated LC-MS/MS method, and HIV-1 RNA were measured in paired CSF and plasma samples 12 weeks after switching. Ten individuals were included. Median (range) age was 42.5 (33-70) years, time on ART was 39.5 (11-197) months, and time with plasma HIV-1 RNA < 40 copies/mL was 15.5 (6-46) months. At baseline, CSF HIV-1 RNA was < 40 copies/mL in all patients. Twelve weeks after switching to ATV/r plus 3TC, HIV-1 RNA remained at < 40 copies/mL in both plasma and CSF in 9/10 patients. One patient with suboptimal adherence to ART had HIV-1 RNA rebound in both plasma and CSF. The median CSF-to-plasma concentration ratios of ATV and 3TC were 0.013 and 0.417, respectively. Median ATV C<sub>24h</sub> in CSF was 10.4 (3.7-33.4) ng/mL (in vitro ATV IC<sub>50</sub> range, 1-11 ng/mL). Median 3TC C<sub>24h</sub> in CSF was 43.4 (16.2-99.3) ng/mL (in vitro 3TC IC<sub>50</sub> range, 0.68-20.6 ng/mL). Most patients maintained HIV-1 RNA in CSF < 40 copies/mL despite CSF ATV C<sub>24h</sub> close to or within the IC<sub>50</sub> range in the majority. ATV PK data in CSF should be considered and rigorous patient selection is advisable to assure effective CSF viral suppression with this two-drug simplification regimen.

Item Type: Article
Uncontrolled Keywords: HIV-1, Antiretroviral therapy, Cerebrospinal fluid, Atazanavir
Depositing User: Symplectic Admin
Date Deposited: 06 Jun 2018 10:36
Last Modified: 01 Feb 2024 18:48
DOI: 10.1007/s13365-018-0626-4
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3022236