Background:  Atazanavir (ATV) exposure may be significantly reduced when co-administered with tenofovir (TDF), or in patients taking proton-pump inhibitors. For this reason, it is advised to prescribe ATV boosted with ritonavir (r or RTV) in these situations. However, the risk of hyperbilirubinemia and jaundice, as well as gastrointestinal disturbances with RTV are increased using ATV/r. Herein, we examined the outcome in patients with plasma HIV RNA <50 copies/mL complaining of side effects under ATV/r 300/100 who were invited to switch to ATV 400 after checking ATV plasma concentrations.

Methods:  All HIV patients under ATV/r complaining of side effects of the medication were offered to enter into a concentration-monitoring protocol. The following inclusion criteria were requested: ATV/r for longer than 6 months, no other protease inhibitor (PI) nor NNRTI combined with ATV/r, plasma HIV RNA <50 copies/mL under ATV/r for >3 months, and calculated C_min for ATV/r >150 ng/mL. Once these criteria were secured, the antiretroviral (ARV) regimen was switch to unboosted ATV (400 mg/day). Laboratory parameters, including ATV-concentration monitoring, were recorded before simplification and every 3 months thereafter until completion of 12 months of follow-up. Mid-dose plasma levels of ATV were determined by high-performance liquid chromatography with ultraviolet detector (HPLC-UV) and reported as calculated C_min.

Results:  A total of 56 patients were switched to unboosted ATV. Median ATV C_min was significantly lower after stopping r compared to baseline (drop from 880 to 283 ng/mL, p = 0.03). While all patients under ATV/r had plasma ATV levels >150 ng/mL, 4 (7%) patients fell below C_min after r removal and in 3 patients RTV was re-introduced. TDF was part of the regimen in these 3 cases. Virologic failure only was recognised in one (2%) patients after switching to unboosted ATV. Median follow-up after simplification to unboosted ATV was 10 months. A total of 29 (52%) patients had grade-3 to -4 hyperbilirubinemia (bilirubin >3.2 mg/dL) while under ATV/r; and declined to 7 (12%) after switching to unboosted ATV (p <0.001).

Conclusions:  Monitoring ATV concentrations is clinically useful to minimize adverse events associated with ATV/r, and permits a switch to unboosted ATV. However, a close follow-up is warranted in patients taking ATV and TDF concomitantly.