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)
88%
men.
Mean
Age 33
CDC
disease stage A 92%
Median
CD4 (IDR) 373 (272-484)
Median
RNA (IQR) 4.77 log, 59,000 copies/ml (4.52-4.90)
20%
of patients had baseline viral load >100,000 copies/ml
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
At
week 48 median CD4 increased 200, and 95% had <400 copies/ml (38/40)
ITT< NC=F).
Serious
adverse events (grade 3-4) were reported in 10 patients:
Elevation
in CPK and LFTs N=2 (Molina said due to exercise before visit)
Hypertrygliceridemia
2
Pregnancy
1
Hospitalization for hernia, nerniated disc, hysterectomy, abscess, and abdominal pain (1 each)
| ADVERSE EVENTS (Grade 1 & 2) |
n=40 |
| Molina
said these events were essentially seen in first 24 weeks. |
|
| Neurosensoral | 32 (80%) |
| D |
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).