|Title:||Cholelithiasis and nephrolithiasis in HIV-positive patients in the era of combination antiretroviral therapy||Authors:||KUAN-YIN LIN
|Issue Date:||2015||Journal Volume:||10||Journal Issue:||9||Start page/Pages:||e0137660||Source:||PLoS ONE||Abstract:||
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 UDPglucuronosyltransferase (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. ? 2015 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
|URI:||https://scholars.lib.ntu.edu.tw/handle/123456789/503501||ISSN:||1932-6203||DOI:||10.1371/journal.pone.0137660||SDG/Keyword:||abacavir; alanine aminotransferase; aspartate aminotransferase; atazanavir; atazanavir plus ritonavir; bilirubin; cholesterol; darunavir; didanosine; glucuronosyltransferase 1A1; indinavir; indinavir plus ritonavir; lopinavir plus ritonavir; multidrug resistance protein 1; nelfinavir; nonnucleoside reverse transcriptase inhibitor; ritonavir; saquinavir; stavudine; tenofovir; triacylglycerol; zalcitabine; zidovudine; anti human immunodeficiency virus agent; adult; Article; bilirubin blood level; body mass; CD4 lymphocyte count; cholelithiasis; cholesterol blood level; cohort analysis; controlled study; drug blood level; drug monitoring; echography; fatty liver; female; gene frequency; genetic polymorphism; genotyping technique; glomerulus filtration rate; hepatitis B; hepatitis C; high performance liquid chromatography; highly active antiretroviral therapy; homosexual male; human; Human immunodeficiency virus infected patient; Human immunodeficiency virus infection; hyperlipidemia; hypertension; incidence; liver cirrhosis; major clinical study; male; medical record review; nephrolithiasis; polymerase chain reaction; prevalence; restriction fragment length polymorphism; retrospective study; risk factor; Taiwanese; urine pH; virus hepatitis; virus load; adverse effects; allele; cholelithiasis; complication; diagnostic imaging; genetic predisposition; genotype; highly active antiretroviral therapy; HIV Infections; Human immunodeficiency virus infection; immunology; middle aged; nephrolithiasis; Taiwan; virology; 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
|Appears in Collections:||醫學檢驗暨生物技術學系|
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