Prevalence and correlates of hyperbilirubinemia in Atazanavir boosted with Ritonavir (ATV/r) recipients PLHIV: A cross-sectional study

Abstract

Background Following rapid advances in antiretroviral therapy (ART), long-term treatment with simple and tolerable regimens has been provided. Protease Inhibitors are important drugs in the ART regimen for the treatment of HIV, with one of the recommended treatments in this class being Atazanavir boosted with Ritonavir (ATV/r). However, hyperbilirubinemia has been reported as an adverse effect of this treatment. Considering the importance and necessity of ART treatment in people living with HIV (PLHIV), this study aimed to investigate the prevalence of hyperbilirubinemia in PLHIV who received ATV/r as an HIV treatment regimen. Methods This cross-sectional study retrospectively examined clinical records of PLHIV in Tehran, Iran, who were receiving Atazanavir/Ritonavir treatment at the Consulting Clinic of Behavioral Disorders of Imam Khomeini Hospital between 2014 and 2020. The records for 121 PLHIV patients were reviewed and relevant data were extracted. Relevant variables included bilirubin tests aligned with drug intake dates, liver enzymes, CD4 count, Hepatitis B, Hepatitis C serology, as well as demographic information and treatment history. Atazanavir/Ritonavir was administered as a second-line treatment in Iran during the study period. The normality of data distribution was assessed by the Kolmogorov-Smirnov test. For normal distributed variables, parametric tests were employed while for non-normal distributed variables, non-parametric tests such as Chi-square were used. Results The majority of study participants were male, with 39.7% testing positive for hepatitis C virus (HCV) antibodies. Hyperbilirubinemia was present in over 85% of the patients, with more than half exhibiting a grade III or higher of indirect hyperbilirubinemia. The prevalence and severity of hyperbilirubinemia were higher when ATV/r was combined with Co-biovir as compared to Truvada. There was no significant difference in hyperbilirubinemia risk between sexes or HCV-Ab positive and negative patients. However, a significant correlation was noted between levels of indirect bilirubin and CD4 cell counts. Conclusions The prevalence and severity of hyperbilirubinemia appear to be associated with CD4 count in PLHIV, while there was no apparent association with gender or age. The choice of drug combined with ATV/r may also influence the occurrence and intensity of hyperbilirubinemia in this clinical population.