Ritonavir-boosted atazanavir may be efficacious in HIV-infected patients concurrently receiving omeprazole.

To the Editor—Optimal absorption of atazanavir is highly dependent upon an acidic gastric pH. In a small study of healthy volunteers, coadministration of omeprazole (40 mg per day) and a combination of atazanavir (300 mg per day) and ritonavir (100 mg per day) reduced the minimum concentration (Cmin) and area under the plasma concentration-time curve (AUC) for atazanavir by 78% and 76%, respectively [1]. Because antiretroviral efficacy of protease inhibitors generally correlates with Cmin and AUC [2], Bristol-Myers Squibb recommended that omeprazole and atazanavir should not be coadministered [3]. However, there are no established pharmacokinetic parameters for atazanavir that predict virologic suppression. In addition, recent data suggest that this adverse omeprazole-atazanavir interaction does not occur in some HIVinfected patients [4, 5]. We describe a 50year-old HIV-infected African American man who maintained virologic suppression with an atazanavir-ritonavir–based regimen despite omeprazole use. The patient’s virologic history included an HIV load of ! 400 copies/mL for the previous 6 years (4 years of stavudinelamivudine-ritonavir–boosted indinavir therapy, followed by 2 years of stavudinelamivudine-nelfinavir therapy). The patient had no genotypic evidence of protease-resistance mutations. Atazanavirritonavir was substituted for nelfinavir because of worsening hyperlipidemia. At that time, the patient’s CD4 cell count was 1095 cells/mL (CD4 cell percentage, 23%) and HIV load was 88 copies/mL. At a follow-up visit 12 weeks later, the patient reported 100% adherence to all antiretroviral drugs but also reported that he had taken atazanavir at a dosage of 150 mg twice per day instead of 300 mg once per day. Furthermore, he had taken omeprazole at a dosage of 20 mg every day (for gastroesophageal reflux disease) concurrently with his morning antiretroviral doses. At the 12-week follow-up visit, the patient had a CD4 cell count of 830 cells/ mL (CD4 cell percentage, 21.2%) and an HIV load of ! 75 copies/mL. After literature review and discussion with the patient, he resumed stavudine-lamivudinenelfinavir therapy, continued omeprazole therapy, and initiated statin therapy. Data regarding the concurrent use of proton pump inhibitors and atazanavir are limited and conflicting. Although no therapeutic drug monitoring was performed for our patient, an HIV load of ! 75 copies/ mL suggests that he did not experience any adverse interaction between omeprazole and atazanavir, despite 12 weeks of coadministration. Several possibilities exist for this observation. First, atazanavir pharmacokinetics and omeprazole-atazanavir pharmacokinetics can vary significantly from person to person, such that adequate atazanavir Cmin and AUC may be achieved for some HIV-infected patients and not for others [4]. Second, our patient had no genotypic evidence of proteaseresistance mutations, and his virus likely retained susceptibility to atazanavir, even at lower drug concentrations. Third, the omeprazole-atazanavir interaction may not compromise virologic outcomes in patients who are already immunosuppressed [5]. Fourth, lower dosages of omeprazole, such as 20 mg per day, may not significantly affect atazanavir absorption [4, 5]. Fifth, the short period of concurrent omeprazole and atazanavir administration may have been insufficient to develop clinical resistance and viral rebound, especially in this patient, who had a high CD4 cell count and longstanding viral suppression. To date, the earliest reported virologic failure occurred after 16 weeks of concurrent therapy [5]. Sixth, it is also conceivable, but less likely, that taking atazanavir twice per day may have blunted the effect of the patient’s morning omeprazole-atazanavir coadministration. These issues were discussed with our patient; he chose to resume nelfinavir treatment, because the available data suggest that there is no adverse pharmacokinetic interaction with omeprazole. His case underscores the need for additional data to conclusively determine the effect of omeprazole and atazanavir coadministration on virologic outcomes in HIV-infected patients.