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One A Day Regimen for HIV: pilot study of FTC,ddI, efavirenz
reported by Jules Levin
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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.
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