Kuan-Yin Lin, Sih-Han Liao, Wen-Chun Liu, Aristine Cheng, Shu-Wen Lin, Sui-Yuan Chang, Mao-Song Tsai, Ching-Hua Kuo, Mon-Ro Wu, Hsiu-Po Wang, Chien-Ching Hung, Shan-Chwen Chang
OBJECTIVES: This study aimed to describe the epidemiology and risk factors of Cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy.
METHODS: We retrospectively reviewed the medical records of HIV-positive patients who underwent routine abdominal sonography for chronic viral hepatitis, fatty liver, or elevated aminotransferases between January 2004 and January 2015. Therapeutic drug monitoring of plasma concentrations of atazanavir was performed and genetic polymorphisms, including UDP-glucuronosyltransferase (UGT) 1A1*28 and multidrug resistance gene 1 (MDR1) G2677T/A, were determined in a subgroup of patients who received ritonavir-boosted or unboosted atazanavir-containing combination antiretroviral therapy. Information on demographics, clinical characteristics, and laboratory testing were collected and analyzed.
RESULTS: During the 11-year study period, 910 patients who underwent routine abdominal sonography were included for analysis. The patients were mostly male (96.9%) with a mean age of 42.2 years and mean body-mass index of 22.9 kg/m2 and 85.8% being on antiretroviral therapy. The anchor antiretroviral agents included non-nucleoside reverse-transcriptase inhibitors (49.3%), unboosted atazanavir (34.4%), ritonavir-boosted lopinavir (20.4%), and ritonavir-boosted atazanavir (5.5%). The overall prevalence of Cholelithiasis and nephrolithiasis was 12.5% and 8.2%, respectively. Among 680 antiretroviral-experienced patients with both baseline and follow-up sonography, the crude incidence of Cholelithiasis and nephrolithiasis was 4.3% and 3.7%, respectively. In multivariate analysis, the independent factors associated with incident Cholelithiasis were exposure to ritonavir-boosted atazanavir for >2 years (adjusted odds ratio [AOR], 6.29; 95% confidence interval [CI], 1.12-35.16) and older age (AOR, 1.04; 95% CI, 1.00-1.09). The positive association between duration of exposure to ritonavir-boosted atazanavir and incident Cholelithiasis was also found (AOR, per 1-year exposure, 1.49; 95% CI, 1.05-2.10). The associated factors with incident nephrolithiasis were hyperlipidemia (AOR, 3.97; 95% CI, 1.32-11.93), hepatitis B or C coinfection (AOR, 3.41; 95% CI, 1.09-10.62), and exposure to abacavir (AOR, 12.01; 95% CI, 1.54-93.54). Of 180 patients who underwent therapeutic drug monitoring of plasma atazanavir concentrations and pharmacogenetic investigations, we found that the atazanavir concentrations and UGT 1A1*28 and MDR1 G2677T/A polymorphisms were not statistically significantly associated with incident Cholelithiasis and nephrolithiasis.
CONCLUSIONS: In HIV-positive patients in the era of combination antiretroviral therapy, a high prevalence of Cholelithiasis and nephrolithiasis was observed, and exposure to ritonavir-boosted atazanavir for >2 years was associated with incident Cholelithiasis.
Adult
Alleles
Anti-HIV Agents
Antiretroviral Therapy, Highly Active
CD4 Lymphocyte Count
Cholelithiasis
Female
Gene Frequency
Genetic Predisposition to Disease
Genotype
HIV Infections
HIV Seropositivity
Humans
Incidence
Male
Middle Aged
Nephrolithiasis
Polymorphism, Genetic
Prevalence
Retrospective Studies
Risk Factors
Taiwan
Ultrasonography
Viral Load
