Jules Levin, NATAP

T-20

Jay Laleazri reported preliminary information on safety and antiviral activity when T-20 was used in combination therapy for a small group of individuals with extensive treatment experience. T-20 is a fusion inhibitor that is administered twice daily by subcutaneous injection. It is a new class of drugs and it’s not expected to have cross-resistance with currently available classes. So it is expected to be of help to individuals with resistance to currently available drugs. Studies are proceeding but their may be a shortage of drug if and when it is approved by FDA for commercial distribution. There may not be enough drug available to meet demand because this type of drug has never been manufactured before and gearing up will be difficult and limited by manufacturing. In this study people with extensive experience with prior treatment received a regimen including T-20. Participants had received T-20 during previous short-term monotherapy studies and patients were off T-20 for a median of 4 months (range 2-8). One-third of patients were on drug holiday when screened for study.

71 participants were enrolled to receive 50 mg T-20 BID by self-administered subcutaneous injections in combination with drugs selected on the basis of genotypic resistance testing. Nine patients had not yet reached 16 weeks; there were 7 discontinuations: 2 deaths due to progression to AIDS, none discontinued due to T-20 related complications. This is primarily a safety study to look secondarily at antiviral activity. Prior to receiving T-20 in this study (n=55) patients had used a median of 11 prior drugs and 93% has used drugs from all 3 classes. In this study patients received on average 4 drugs in addition to T-20.

Median baseline VL was 80,000 copies/ml and CD4s of 70. The study participants had been heavily pre-treated. Percentage of patients with genotypic mutations associated with NRTIs was 82%, 60% for NNRTIs, and 93% for protease inhibitors. 100% had PI experience. 93% had experience with NNRTIs,, NRTIs, and protease inhibitors. In this latter group, 55% had mutations at baseline with an average of 13 mutations.

Viral Load Results-- At 16 weeks, 60% (33/55) had VL reductions >1 log and/or <400 copies/ml, 36% (20/55) had <400 copies/ml, and 20% had < 50 copies/ml using on-treatment analysis. The ITT analysis was about the same. Individuals with triple class exposure and documented triple class resistance also had similar results. Although the data was not shown Lelazari said there was no difference in outcome between those who took drug holidays and those who did not.

At week 16, a -1.2 log reduction in viral load was seen in the as-treated, triple class exposure and triple resistance arms. Lalezari suggests this reveals the effect of T-20. Additionally, he showed a slide suggested the viral load reductions of T-20 were independent of baseline viral load and the number of drugs in a person’s regimen in the study. Lalezari concluded T-20 can be an effective antiviral drug in HIV treatment.

Commentary-- Because T-20 was used in this study as part of a multi-drug combination it may be difficult to characterize its effect but in previous short-term studies the antiviral activity of T-20 has been seen.

Safety Results-- 7 patients had stopped therapy. No withdrawals to date have been due to adverse events considered related to T-20. 15% had grade 3 events possibly related to T-20 but no one person experienced more than 1 event so Lalezari said he didn’t feel there was a trend showing association. There were 5 serious adverse events (7%) possibly related to T-20 but Lalezari did not feel there was reason to believe they were associated with T-20: elevated SGPT, elevated amylase, nausea & vomiting, neutropenia, anemia. 67% of patients reported mild transient injection site reactions. Lalezari concluded T-20 is safe and well tolerated as a twice-a-day injection for 16 weeks in combination therapy.