Effectiveness and tolerability of a once-daily amprenavir/ritonavir-containing highly active antiretroviral therapy regimen in antiretroviral-naïve patients at risk for nonadherence: 48-week results after 24 weeks of directly observed therapy.
OBJECTIVES: To determine the safety and effectiveness of a once-daily highly active antiretroviral therapy (HAART) regimen in patients at risk for poor adherence using directly observed therapy (DOT) for 24 weeks followed by weekly phone contact for another 24 weeks. METHODS: A prospective, open-label pilot study was carried out. Antiretroviral-naïve patients with advanced HIV disease were treated with once-daily amprenavir 1200 mg, ritonavir 200 mg, didanosine 400 mg and lamivudine 300 mg. After 24 weeks, DOT was substituted by weekly phone contact. Measurements of viral load and CD4 cell count, and safety laboratory measurements, were taken regularly for 48 weeks. RESULTS: Twenty-two patients were enrolled in the study, of whom 19 completed at least 4 weeks of treatment. Seventeen patients completed 24 weeks and 13 completed 48 weeks. None discontinued treatment as a result of adverse events. The median baseline HIV viral load was 5.29 log(10) HIV-1 RNA copies/mL and the median CD4 cell count was 20 cells/microL. At weeks 24 and 48, 74% of the patients had viral loads <400 copies/mL. At 48 weeks, the median decrease in viral load from baseline was 3.06 log(10) copies/mL, and the median increase in CD4 cell count was 118 cells/microL. The median trough plasma amprenavir concentrations at weeks 1 and 24 were 1.87 and 1.42 microg/mL, respectively. CONCLUSIONS: This study suggests that DOT followed by weekly patient contact results in good treatment outcome in this challenging population. The median trough plasma amprenavir concentrations were above the effective concentration of drug that resulted in 90% inhibition of viral load in vivo (EC(90)) for wild-type HIV.