Atazanavir and Acid-Lowering Therapy: RESULTS part 3
Case reports have also yielded conflicting results. In one such report, an HIV-infected patient underwent a 12-h pharmacokinetic study, which supported an interaction between the PPI (esomeprazole) and atazanavir. The 65-year-old patient was receiving an antiretroviral regimen consisting of atazanavir 300 mg with ritonavir 100 mg daily, tenofovir 300 mg daily, and stavudine 30 mg twice daily. The 12-h pharmacokinetic sampling revealed a 90% reduction in Cmin and a 78% reduction in AUC relative to established therapeutic ranges of concentrations reported in clinical trials of atazanavir. On the basis of these results, the clinicians caring for the patient increased the dosing regimen to atazanavir 300 mg bid with ritonavir 100 mg bid, but there was no significant improvement in Cmin. The patient’s antiretroviral regimen was subsequently changed; no information on clinical outcome was reported.
An earlier case that minimized the atazanavir-PPI interaction was reported by Kosel and others. A 40-year-old HIV-infected man was receiving lansoprazole 30 mg bid for gastroesophageal reflux disease and Barrett’s esophagitis before initiation of antiretroviral therapy. At the time of initiation of the antiretroviral regimen (which consisted of atazanavir 300 mg with ritonavir 100 mg daily, tenofovir 300 mg daily, and lamivudine 300 mg daily), ranitidine was substituted for lansoprazole to avoid the potential interaction between the PPI and atazanavir. Because of therapeutic failure with ranitidine, lansoprazole was restarted 1 month later. The patient’s serum atazanavir concentrations were within the target ranges suggested for use of ritonavir- boosted atazanavir with concomitant tenofovir. Cmax was 4120 ng/mL (target value when atazanavir is used with PPIs and tenofovir = 3443 ±1412 ng/mL), and Cmm was 790 ng/mL (target value when used with PPIs and tenofovir = 577 ± 367 ng/mL). No clinical outcomes were reported.
The clinical outcomes associated with atazanavir and concomitant PPI therapy were described in a case report by Chan-Tack and Edozien. Virological suppression was maintained in a 50-year-old HIV-infected African- American man with an atazanavir-based regimen, despite concomitant PPI use. Before starting the atazanavir, the patient had received an antiretroviral regimen containing stavudine, lamivudine, and ritonavir-boosted indinavir for 4 years, followed by 2 years of therapy with a regimen containing stavudine, lamivudine, and nelfinavir; during that time, his viral load remained below 400 copies/mL. Eventually, atazanavir was substituted for nelfinavir because of worsening hyperlipidemia. At the time of the change, the patient’s CD4 count was 1095 cells/mm3 (CD4 percentage = 23%), and the viral load was 88 copies/mL. After 12 weeks, the patient reported 100% adherence but revealed that he was taking omeprazole 20 mg daily for gastroesophageal reflux disease and also that he was taking his atazanavir divided in 2 doses rather than 300 mg once daily as prescribed. At this 12-week follow-up, his CD4 count remained at 830 cells/mm3 (CD4 percentage = 21%), and viral load was less than 75 copies/mL. Despite the lack of adverse clinical outcome, the patient was switched back to a nelfinavir-containing regimen, along with initiation of statin therapy.
In the final case report identified, the effects on both pharmacokinetic and clinical outcomes were described for a patient receiving atazanavir and PPI therapy. A 56-year-old HIV-infected man with a CD4 count of 494 cells/mm3 and an HIV RNA load of 64 800 copies/mL initiated a regimen containing atazanavir boosted with ritonavir and tenofovir, along with abacavir and lamivudine. Two months after initiation of this regimen, gastritis developed, which was unresponsive to H2 antagonists; thus, omeprazole 40 mg daily was required. Over the next 10 months, despite concomitant PPI therapy, the patient’s viral load remained at or less than 50 copies/mL. An atazanavir trough level, measured in a sample drawn during PPI coadministration about 22 h after an unwitnessed dose of atazanavir, was 0.3 mg/L; this value was below the population-predicted 25th percentile for ritonavir-boosted atazanavir but above the 75th percentile for unboosted atazanavir. As unboosted atazanavir has been shown to achieve rates of viral control similar to those obtained with ritonavir-boosted atazanavir in treatment-naive patients, the authors considered the measured level adequate. levitra plus