Safety and efficacy of ritonavir and saquinavir in combination with zidovudine and lamivudine

Background: Ritonavir is a potent inhibitor of cytochrome P4503A4 that stro ngly increases saquinavir bioavailability, In this study we assessed the sa fety and antiretroviral efficacy of the combination of these two compounds in patients pretreated and receiving continued treatment with zidovudine an d lamivudine who were protease inhibitor naive and who had a CD4 cell count s below 200/mm(3). Methods: In this 48-week pilot study, all patients received 600 mg ritonavi r and 400 mg saquinavir twice daily. Administration of zidovudine and lamiv udine was continued without a change in previous doses. Viral load, CD4 cel l count, and the emergence of resistance to the two protease inhibitors wer e evaluated repeatedly up to week 48. Results: Sixteen patients were included in the study. Previous nucleoside a nalog treatment duration was 48 +/- 22 months (mean +/- SD), Two patients q uit taking both protease inhibitors within 2 weeks. The ritonavir dose had to be reduced in 10 other patients because of side effects. Between inclusi on and week 48, plasma viremia varied from 4.87 +/- 0.43 to 3.00 +/- 1.29 l og(10) copies/mL and CD4 cell counts ranged from 98 +/- 61 to 250 +/- 139/m m(3). Ten patients (63%) had viral loads below 200 copies/mL and 7 (44%) ha d viral loads below 50 copies/mL. A single key mutation that conferred rito navir resistance I84V and V82A/V developed in two patients. A mutation at c odon 54 developed in another patient. These mutations were associated with repeated cessations of antiretroviral treatment. No lipodystrophy was obser ved. Conclusion: Ritonavir and saquinavir in combination are quite well tolerate d and induce a high and sustained antiretroviral efficacy. A four-drug comb ination that includes these two protease inhibitors should be considered as a first line of treatment in patients with low CD4 cell counts.