Potential association between rosuvastatin use and high atazanavir trough concentrations in ritonavir-treated HIV-infected patients

BACKGROUND: Emerging evidence shows that standard atazanavir (ATV) dosages are associated with considerable interindividual variability in plasma drug concentrations. Given the potential impact of ATV exposure on clinical outcome, in this retrospective study we sought to assess demographic and clinical factors influencing ATV plasma concentrations in a large cohort of HIV-infected patients. METHODS: HIV-infected patients treated with ATV for at least 3 months and with at least one assessment of ATV trough concentrations were enrolled. Blood trough samples were collected from all patients immediately before the next drug intake. Plasma ATV and ritonavir concentrations were quantified by a validated chromatographic method coupled with tandem mass spectrometric detection. Univariate and multivariate regression analyses were performed using ATV plasma concentrations as the dependent variable, with demographic and clinical characteristics as the independent ones. RESULTS: A total of 273 HIV-infected adult patients were included in the present study. Factors significantly associated with increased ATV concentrations by univariate analysis were ATV dosage, number of concomitant drugs, ritonavir or statin use. However, with multivariate regression analysis, the only factors independently and significantly associated with ATV concentrations were ritonavir use (r=0.291, P<0.0001) and concomitant rosuvastatin therapy (r=0.315, P<0.0001). CONCLUSIONS: We found that patients on ATV/ritonavir given rosuvastatin concomitantly have ATV concentrations that exceed the upper therapeutic threshold of 800 ng/ml known to be associated with a high risk of experiencing ATV-related side effects. In agreement with previous findings we confirmed the lack of association between other demographic and clinical characteristics such as age, gender, body weight and ATV exposure.