Report 1 from Glasgow, Scotland
The 5th International Congress on Drug Therapy in HIV Infection
Day One at Glasgow

Once A Day Regimen: Efavirenz + DDI and 3TC or FTC

As usually happens every year at the Glagow Conference, the first day consists of pharmaceutical satellite symposiums. Today we heard from Glaxo Wellcome, DuPont, and Roche. At the DuPont symposium, Jean-Michel Molina and a French research group reported 48 week follow-up results from the Montana Trial (ANRS 091). This was an open-label, single-arm, multi-center trial. The regimen was once daily combination therapy with FTC(200 mg) + ddI (400 mg if 60 kg, 250 mg if <60 kg) + Efavirenz (600 mg). All drugs were taken at bedtime. Patients were treatment-naÔve, CD4s >100, and viral Load >5,000. Virologic success was defined as plasma HIV-RNA <400 copies/ml at week 24. The sample size (n=40) was calculated to abandon this treatment strategy if more than 6 patients had a virologic failure (lower bound of the CI of the proportion of virologic success at week 24 was <70%). Analysis performed was Intent-To-Treat.

BASELINE CHARACTERISTICS (n=40)

All patients received medications, and none were lost to follow-up. Four patients discontinued study by week 48 (2 patients due to intolerance, 1 due to ddI and 1 due to EFV; 1 patient for virologic failure and Molina reported patient was non-compliant; 1 patient chose to withdraw).

RESULTS

ADVERSE EVENTS (Grade 1 & 2) 

n=40  

Molina said these events were essentially seen in first 24 weeks.  
Neurosensoral 32 (80%) 
Dizziness 18  
Sleep disturbances 12  
Depression/mood changes 11
Asthenia 8
Headaches 8
Diarrhea 13 (33%) self-limited  
Maculpopular rash  4 (10%)  
 
GRADE 2 LAB TOXICITIES   n=40  
Hypertriglyceridemia 4 (10%)  
CPK elevations 3 (7.5%)  
Hyperamylasemia  2 (5%
Hypercholesterolemia 1 (2.5%)
Neutropenia 1 (2.5%)  
Gamma GT elevation 1 (2.5%) 

Once Daily DDI+ 3TC + Efavirenz

Franco Maggiolo and an Itlaian research group updated on this study from a Durban report. This study used dosing of ddI 300 mg. Once daily 3TC was used based on intracellular half-life of 15-16 hours (Moore KH et al. AIDS 1999, 13; 2239-2250). Study enrolled 77 treatment naÔve patients with median HIV-RNA of 135,000 copies/ml and mean CD4 of 264, and 51.9% were HCV+. 38 were IVDUs, 6 homosexual, and 33 heterosexual.

After 48 weeks, 75% (ITT) had <50 copies/ml and 93% As-Treated. Median viral load reduction was 3.44 log. Mean CD4 increased from 250 to 449. At week 48, 70% with <100,000 viral load at baseline had <50 copies/ml and 80% with >100,000 copies/ml had <50 copies/ml. But it took longer for people with baseline viral load >100,000 to reach <50 copies/ml (ITT): at week 4 10% with >100,000 at baseline had <50 and 50% with <100,000 at baseline had <50.

There were 3 virologic failures (3 patients had the 184 3TC mutation and 2/3 had the 103 EFV mutation). 12/77 (15.6%) dropped out of study: rash (n=2), GI symptoms (1), gastric intolerance to ddI (1), CNS symptoms (1), non-adherence to therapy (3), death unrelated to HIV or therapy (1).