T-20, the first of a new antiretroviral class called fusion inhibitors, may prove a useful new weapon for people who have tried existing therapeutic options. Data from a phase II salvage study, T-20-205, were presented at the 13th International Conference on AIDS in Durban today.
The North American study involved 71 people, 97% of whom had experience of protease inhibitors, and 79% of whom were experienced with all three currently used HIV drug classes. The median number of prior antiretrovirals taken was nine.
At study entry, the median CD4 count was 90 cells, and the median viral load was 5 log (100,000 copies), reflecting the advanced nature of this study population. This was an uncontrolled study where all participants received T-20. In addition, participants began a ‘background’ regimen that was selected according to the results of a genotypic drug resistance test. On average, participants took five additional antiretrovirals alongside T-20.
Over the 48 weeks of study, 30 people discontinued treatment: 14 for virological failure, 7 for voluntary withdrawal, 4 were lost to follow-up, 3 for adverse events (none of which were related to T-20), and 2 for non-compliance.
Overall, T-20 was described as well-tolerated though 71% experienced mild to moderate injection site reactions (T-20 is administered via a sub-cutaneous injection). 21% of participants suffered grade 3 events that may have been related to T-20, and 10% of serious adverse events were possibly related to T-20.
After 48 weeks, considering data only from those 41 people who remained on T-20, 22% had viral load below 50 copies, 39% were below 400 copies, and 61% had maintained a viral load that was at least one log below their baseline level.
In an intent to treat analysis, which includes data on all participants regardless of whether they dropped out before the 48 week period, 13% had viral load below 50 copies, 23% below 400 copies, and 33% maintained at a least a one log drop in viral load from baseline.
Given the study design, it is impossible to tease out the precise effect that T-20 brought to the overall efficacy of participants’ antiretroviral regimens. Authors assumed that physicians selected additional drugs with regard to genotypic resistance test results, and that no drug that would not be expected to be contribute antiviral activity would be chosen. When the viral load responses were analysed according to the number of additional drugs taken, there was no evidence of a greater effect in those taking larger numbers of drugs. Nevertheless, it makes intuitive sense to presume that those with less drug experience, and particularly those able to add another new drug class, may have gained most benefit from the use of T-20.
Based on these promising data, T-20 is expected to enter phase III study in the US and Europe within the next few months.
Lalezari J et al. Forty-eight week analysis of patients receiving T-20 as a component of multi-drug salvage therapy. 13th International Conference on AIDS, abstract LbPp116, Durban, 9-14 July 2000.