1st International AIDS Society (IAS) Conference on HIV Pathogenesis and Treatment
July 7-11, 2001
Buenos Aires, Argentina
3 Year Durability of Efavirenz in the 006 Study
At the IAS Conference in Buenos Aires, Karen Tashima (Miriam Hospital, Providence, RI) reported data at 96 and 144 weeks on efavirenz (EFV) from the first big study of efavirenz (study 006) conducted by DuPont. This was a large multicenter, open-label, randomized trial comparing EFV+AZT/3TC to indinavir (IDV 800mg every 8 hrs)+AZT/3TC and also to EFV/IDV (IDV 1000mg every 8 hrs). The original cohort enrolled 450 patients but at week 96 patients were asked to re-enroll in the study and a number of them discontinued, so week 96 data on the original cohort may better reflect response to therapy while week 144 may reflect better the discontinuations. In order to collect better data on duration of treatment effect DuPont started an extended cohort several months after the initial cohort enrolled. The total of both cohorts is 1266 patients.
The purpose of this analysis is to report on the durability of response to EFV+AZT/3TC.
There are two noteworthy summary points from this study worth mentioning upfront: (1) some patients can still be experiencing nervous system symptoms after 2 years on EFV therapy. (2) Patients with >100,000 copies/ml of viral load appear to respond as well to therapy (with 3 years follow-up so far) as patients with <100,000 copies/ml of viral load before starting therapy.
Baseline viral load was 4.7 log (50,000 copies/ml) cd4 was 340
Time To Treatment Failure (TTF) is defined as 0 days for patients who were never dosed or who never had viral load <50 copies (complete failures). TTF is the time from start of treatment until a viral load rebound above 50 copies/ml, an AIDS-defining event, or discontinuing from the study for any reason for patients who had achieved viral load <50 copies/ml.
Duration of Response is the time from start of viral suppression <50 copies/ml to the time of TTF. This was reported in one of two ways: all reasons for failure (discontinued from the study for any reason or virologic failure >50 copies on 2 consecutive occasions; and virologic failure only
We all know the difficulties of remaining on an IDV three times per day regimen over the long term considering the adherence difficulties and the side effects, toxicities, and dietary & hydration requirements. IDV is often chosen as a comparison regimen in studies because it is difficult to stay on although it is potent.
Treatment related, new adverse events that were reported between weeks 72-144
Selected adverse events on interest:
Number of patients with nervous system symptoms: after 1-2 years on EFV a small percent of patients (5% in this study) may still be experiencing nervous system symptoms
In the first month after starting treatment about 45% of patients reported nervous system symptoms in the EFV/AZT/3TC arm. This compares to about 10% in the IDV arm and about 38% in the EFV/IDV arm. 4 patients in the EFV arm discontinued due to these symptoms within the first 28 days, which is a rate just under 10% (4/45) for those who experienced such symptoms, or 1% for the total number of patients received the regimen (4/412). After about 1 year of treatment in study, 5-10% on EFV arm were experiencing nervous system symptoms and the total number of patients reported to have 6 discontinued from the EFV arm due to these symptoms was 6. In clinical practice you might expect these numbers to be higher. Interestingly, after almost two years (645 days) still about 5% of patients receiving EFV/AZT/3TC were reported to be experiencing nervous system symptoms. Again, this percent would be expected to be higher in clinical practice.
Discontinuations between weeks 72-144 for EFV/AZT/3TC:
These types of numbers are much lower under study conditions. In real clinical practice these numbers will be much greater for various reasons including adherence and willingness to tolerate regimentation and side effects tends to be more of a problem outside of closely monitored study conditions.