Once-daily regimen of saquinavir, ritonavir, didanosine, and lamivudine in HIV-infected patients with standard tuberculosis therapy (TBQD Study)

Abstract

Objectives: To assess the efficacy and safety of a once-daily regimen with didanosine, lamivudine, saquinavir, and low-dose ritonavir in antiretroviral (ARV)-naive patients with tuberculosis treated with rifampin and the influence of rifampin on plasma trough concentration (Ctrough) of saquinavir.

Methods: Single-arm, prospective, multicenter, open-label pilot study, including 32 adult ARV-naive subjects with HIV infection and tuberculosis under standard treatment that included rifampin (600 mg q.d.) and isoniazid (300 mg q.d.). After 2 months of tuberculosis treatment, patients were started on once-daily ARV therapy, consisting of didanosine, lamivudine, ritonavir (200 mg), and saquinavir soft gel capsules (1600 mg). HIV RNA level, CD4 cell count, clinical and laboratory toxicity, and saquinavir Ctrough during and after antituberculosis therapy were analyzed.

Results: After 48 weeks of follow-up, 20 of 32 patients (62.5%; 95% CI: 45.8% to 79.2%) in the intent-to-treat population and 20 of 28 (71.4%; 95% CI: 54.4% to 88.4%) in the on-treatment population had an HIV RNA level <50 copies/mL. Treatment tolerance was acceptable in all patients except for 2 with biologic hepatic toxicity leading to discontinuation. Seven patients had virologic failure. In 10 patients (36%), saquinavir Ctrough was <0.05 microg/mL during tuberculosis therapy and 5 of them had virologic failure. The median saquinavir Ctrough was 44% lower (interquartile range: 19% to 71%) with coadministration of rifampin than without.

Conclusion: The combination of didanosine, lamivudine, saquinavir, and ritonavir may be a useful treatment regimen for patients with tuberculosis in whom a once-daily protease inhibitor-containing regimen is considered indicated. Nevertheless, on the basis of pharmacokinetic profile the dose of 1600/200 mg of saquinavir/ritonavir cannot be recommended. Further studies with higher doses of saquinavir (2000 mg) boosted with ritonavir are warranted.