Long-term efficacy and safety of ritonavir/indinavir at 400/400 mg twice a day in combination with two nucleoside reverse transcriptase inhibitors as first line antiretroviral therapy.

OBJECTIVE: To determine the long-term antiretroviral efficacy and tolerability of dual protease inhibitor (PI) therapy with indinavir (IDV)/ritonavir (RTV) at 400/400 mg twice a day (BID) in combination with two nucleoside reverse trancriptase inhibitors (NRTIs). DESIGN AND METHODS: In an open-label, uncontrolled multicentre clinical trial, antiretroviral therapy naive patients (n = 93) with a high median baseline HIV-1 RNA level of 210 000 copies/mL (range 17 000-2 943 000) and a median CD4 cell count of 195 copies/microL (range 4-656 copies/microL) were started on a regimen of either zidovudine (ZDV)/lamivudine (3TC) (49%), stavudine (d4T)/3TC (38%) or d4T/didanosine (ddI) (14%) plus RTV and IDV, each at 400 mg BID. CD4 cell counts and HIV RNA were determined at 4-week intervals for a duration of 72 weeks. Statistical analysis was performed on treatment as well as by intent to treat, where missing values were counted as failures.
RESULTS: HIV RNA levels below the limit of detection were achieved in 59.5% (< 80 copies/mL) and 63% (< 500 copies/mL) of patients according to the intent to treat analysis at week 72. In the on treatment analysis, the proportion of patients reaching an undetectable viral load was 94.5% (< 80 copies/mL) and 100% (< 500 copies/mL), respectively. Apart from diarrhoea and nausea, serum lipid abnormalities were identified as the most prominent adverse reaction. No cases of nephrotoxicity occurred during the entire observation period of 72 weeks.
CONCLUSIONS: Our results demonstrate that quadruple therapy with RTV/IDV and two NRTIs induces potent, durable and safe HIV suppression and might be particularly beneficial as a first line therapy for patients with a high baseline viral load.