Is Ritonavir-Boosted Atazanavir a Risk for Cholelithiasis Compared to Other Protease Inhibitors?

Abstract

ObjectiveTo compare the incidence of complicated cholelithiasis in patients receiving ritonavir-boosted atazanavir (ATV/r)- containing antiretroviral therapy with those on other protease inhibitors (PIs).DesignWe conducted a single-center retrospective cohort study of patients who started either ritonavir-boosted ATV/r- or other PIs (ritonavir-boosted fosamprenavir, unboosted fosamprenavir, lopinavir/ritonavir, and ritonavir-boosted darunavir) -containing antiretroviral therapy.MethodsThe incidence of complicated cholelithiasis was determined in each group. Complicated cholelithiasis was defined as follows: 1) cholelithiasis complicated by cholecystitis, cholangitis, or pancreatitis or 2) symptomatic cholelithiasis or choledocholithiasis which required invasive procedures such as cholecystomy and endoscopic retrograde cholangiopancreatography. The effects of ATV/r were estimated by univariate and multivariate Cox hazards models as the primary exposure.ResultsComplicated cholelithiasis was diagnosed in 3 patients (2.23 per 1000 person-years) in the ATV/r group (n = 466), and 3 (1.64 per 1000 person-years) in the other PIs group (n = 776), respectively. The incidence was not statistically different in the two groups by log-rank test (P = 0.702). By univariate and multivariate analysis adjusted for age and body weight, ATV/r use was not associated with cholelithiasis. (HR = 1.365; 95% CI, 0.275–6.775; p = 0.704) (adjusted HR = 1.390; 95% CI, 0.276–7.017; p = 0.690). For the 3 patients who developed cholelithiasis in the ATV/r group, the time to the diagnosis of cholelithiasis was 18, 34, and 39 months, respectively.ConclusionIn this study, the incidence of complicated cholelithiasis was low and was not different between patients on ATV/r and those on other PIs. On the contrary to ATV/r-associated nephrolithiasis, the possible risk of cholelithiasis should not preclude the use of ATV/r.

Metabolic and Kidney Disorders Correlate with High Atazanavir Concentrations in HIV-Infected Patients: Is It Time to Revise Atazanavir Dosages?

“…The potential association between exposure to ATV and increased risk to cholelithiasis is still a matter of debate. Indeed, Hamada and co-workers reported a low incidence of complicated cholelitiasis in patients on ATV comparable to other PIs [ 30 ]. These results have been partially challenged by recent findings from the same authors [ 31 ] reporting an increased risk of cholelithiasis in patients treated with ATV for more than two years.…”

PharmGKB summary

“…In line with these findings, a retrospective observational study of fourteen patients treated with ATV who had developed complicated cholelithiasis reported that in four patients, 100% of the biliary calculi was made up of ATV [65]. Incidence of cholelithiasis has not been found to differ between patients treated with ATV/r and those treated with other protease inhibitors boosted with ritonavir [66]. One retrospective pharmacogenetic study of 910 HIV-positive individuals who had undergone therapeutic drug monitoring and abdominal sonography reported no association between either UGT1A1 *28 or rs2032582 (c. c.2677 A>C/T) in ABCB1 (also known as MDR1 2677A>C/T) with risk of cholelithiasis [7].…”

Antiretroviral treatment for HIV infection: Swedish recommendations 2019

“…Atazanavir has an increased risk of developing galland kidney stones over time [38,39] and icterus due to inhibition of the enzyme UGT1A is a common adverse effect. Another disadvantage of atazanavir is the decreased absorption seen in increasing pH, which means atazanavir should not be combined with proton pump inhibitors.…”