icon_folder.gif   Conference Reports for NATAP  
  8th European Conference on Clinical Aspects and treatment of HIV-Infection (ECCATHI)
Athens, Greece - October 2001
Back grey_arrow_rt.gif
One A Day Regimen for HIV: pilot study of FTC,ddI, efavirenz
reported by Jules Levin
  Jean-Michel Molina from Paris reported at ECCATHI in Athens (October 2001) on an open-label pilot study of a completely one-a-day regimen. ANRS 091 is an ongoing study of 40 treatment-naive patients in which all patients receive FTC (200 mg), Sustiva (600 mg), and ddI (400 mg if >60 kg; 250 mg if <60 kg), all drugs taken once per day. Molina reported results after 96 weeks of the study. Median baseline viral load was 59,000 copies/ml (4.77 log) and CD4 was 373. Patients were asked to take the medications at bedtime (7 pills/day) on an empty stomach.
At week 96, 85% (34/40) of patients had viral load <400 copies/ml and 80% had <50 copies/ml (ITT, non-completer=failure). The median CD4 increase was 272 cells at week 96. Molina reported that the most common treatment related adverse events occurred during the first 24 weeks of the study, and were mild to moderate central nervous system symptoms (73% of patients), diarrhea (37% of patients), rashes (10%), and biochemical abnormalities. Also, there were 22 serious adverse events reported in 16 patients, but reportedly only 4 were possibly treatment related (grade 3 hypertriglyceridemia in 2 and grade 3 transaminases in 2 [liver enzymes]). It was also reported that 8/9 patients with a baseline viral load >100,000 copies/ml had <400 copies/ml at week 96.
A pharmacokinetic sub-study was conducted to investigate the PK of FTC, ddI, and Sustiva when administered once per day. The purpose was to see if drug levels for each drug in the blood are negatively affected. After 4 weeks of taking study drugs 9 patients in this study skipped their treatment at bedtime and took their next dose in the morning. The pharmacokinetics of each drug were compared with historical controls (what they've seen from past studies) where each drug was administered alone. The investigators reported the results showed no significant alterations in the PK of any of the drugs, and plasma viral load remained <50 copies/ml in all 9 patients from week 24-64.
Median PK parameters for FTC, ddI, and Sustiva respectively, were: AUC0-24: 7.3, 7.4, and 72 h* mcg/ml; Cmax: 1.7, 2.6, 2.5 mcg/ml; Cmin: 0.04, <0.01, and 1 mcg/ml; Tmax: 1.5, 1.1, 2.5 h; t1/2: 7.6, 2.3, 2.0 h. Molina also reported that the PK data obtained in this study may have been slightly underestimated due to the 36-hour dosing interval immediately prior to the PK evaluation. The authors concluded that this PK data supports the use of FTC, ddI, and Sustiva administration in a once per day regimen.