title: Cholelithiasis and Nephrolithiasis in HIV-Positive Patients in the Era of Combination Antiretroviral Therapy.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Taipei City Hospital, Kun-Ming Branch, Taipei, Taiwan.
authors.forename: Kuan-Yin
authors.initials: KY
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
authors.forename: Sih-Han
authors.initials: SH
authors.lastname: Liao
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
authors.forename: Aristine
authors.initials: A
authors.lastname: Cheng
authors.affiliation: Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Lin
authors.affiliation: Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Sui-Yuan
authors.initials: SY
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors.forename: Mao-Song
authors.initials: MS
authors.lastname: Tsai
authors.affiliation: Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; School of Pharmacy, National Taiwan University, Taipei, Taiwan.
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Kuo
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Mon-Ro
authors.initials: MR
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Hsiu-Po
authors.initials: HP
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; China Medical University, Taichung, Taiwan.
authors.forename: Chien-Ching
authors.initials: CC
authors.lastname: Hung
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Shan-Chwen
authors.initials: SC
authors.lastname: Chang
mesh_terms: D000328:Adult; D000483:Alleles; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D002769:Cholelithiasis / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D006679:HIV Seropositivity; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D053040:Nephrolithiasis / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000209:etiology*; D011110:Polymorphism, Genetic; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D014463:Ultrasonography; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents