Abstract
ObjectivesThis study aimed to describe the epidemiology and risk factors of cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy.MethodsWe 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.ResultsDuring 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.ConclusionsIn 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.
Highlights
Both cholelithiasis and nephrolithiasis are widespread conditions constituting a major health burden, affecting an estimated 10–15% and 2–20% of the adult population, respectively [1]
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 multidrug resistance gene 1 (MDR1) G2677T/A polymorphisms were not statistically significantly associated with incident cholelithiasis and nephrolithiasis
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
Summary
Both cholelithiasis and nephrolithiasis are widespread conditions constituting a major health burden, affecting an estimated 10–15% and 2–20% of the adult population, respectively [1]. The prevalence and incidence of cholelithiasis and nephrolithiasis vary with geographic locations and have increased over the past decades [2,3]. The increasing rates of cholelithiasis and nephrolithiasis are multifactorial, and several demographic and metabolic factors have been identified as risk factors [1]. Few studies have investigated the epidemiology of cholelithiasis and nephrolithiasis in people infected with HIV [4,5]. Ritonavirboosted atazanavir (atazanavir/ritonavir) has been associated with cholelithiasis and nephrolithiasis [4,7,8]. The impact of atazanavir/ritonavir exposure on cholelithiasis and nephrolithiasis remains difficult to estimate since screening methods using sonography were not routinely performed [9]
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