Efficacy and safety of twice daily first-line ritonavir/indinavir plus double nucleoside combination therapy in HIV-infected individuals.

Objective: To evaluate the virological efficacy and safety of quadruple therapy with two nucleoside analogues and ritonavir (400 mg twice daily) plus indinavir (400 mg twice daily) combination in antiretroviral therapy-naive patients. Design and methods: An open-label, uncontrolled multicentre trial. Antiretroviral therapy-naive patients (n = 90) with high median baseline HIV RNA levels of 220 000 copies/ml (range, 36 000-2 943 000 copies/ml) and median CD4 cell count of 189 × 10 6 /l (range, 4-656 × 10 6 /l) were started on a twice daily regimen of either zidovudine/lamivudine (49%), stavudine/lamivudine (38%) or stavudine/didanosine (13%) plus ritonavir 400 mg twice daily and indinavir 400 mg twice daily combination therapy. CD4 cell counts and HIV RNA were determined at weeks 0, 4, 8, 12, 16, 20, and 24. Statistical analysis was performed on treatment as well as intent-to-treat, where missing values were accounted for as failure. Results: In the intent-to-treat analysis at week 24, the proportion of patients with HIV RNA of < 500 copies/ml, and < 80 copies/ml was 86.7% and 71.1%, respectively. In the on-treatment analysis at week 24, 80.0% of patients had undetectable viral load in the ultrasensitive assay (< 80 copies/ml; n = 80). The quadruple therapy was well tolerated except for mild diarrhoea, initial nausea and increased triglyceride levels. Treatment was stopped in seven (7.7%) patients because of adverse events and three (3.3%) were lost to follow-up. Conclusions: Our preliminary data suggest that the protease inhibitor combination ritonavir/indinavir plus double nucleoside therapy appears to be effective and safe in short-term treatment (up to 24 weeks).