The experimental anti-HIV drug enfuvirtide is an effective salvage therapy for treatment-experienced people, according to data presented today at the Fourteenth International AIDS Society in Barcelona.
Two similar studies, presented during the late breaker session, indicate that adding enfuvirtide to a new salvage regimen can provide significant virological benefit.
Formerly known as T-20, enfuvirtide is the newest anti-HIV drug to emerge from the treatment pipeline. It belongs to a novel class of drugs called fusion inhibitors. This class targets the bonding between immune cells and HIV which facilitates HIV entry into uninfected cells.
Dr Keith Henry presented TORO 2 (T-20 versus Optimised Regimen Only) which compared an optimised salvage regimen of currently available drugs with an optimised salvage regimen plus enfuvirtide. Participants were highly treatment experienced, having taken multiple drugs from each of the three drug classes. Baseline median CD4 cell count was 80 and median viral load was 5.2 log. Optimised background regimens were selected using resistance testing data and previous drug history.
After 24 weeks of treatment, intention-to-treat analysis showed that 51% of 326 enfuvirtide recipients achieved at least a 1 log reduction in viral load compared to 29% of the control arm. Furthermore, 37% and 20% of people in the enfuvirtide arm had a viral load below 400 and 50 copies/ml, respectively, compared to 16% and 7% in the control arm. Overall the average reduction in viral load was -1.70 log versus -0.76 log (p
TORO 1 compared enfuvirtide plus optimised background therapy versus optimised background therapy alone in 504 highly treatment experienced people. In this study, median baseline viral load was 5.1 log and median CD4 cell count was 98. Dr B. Clotet reported that the average reduction in viral load at week 24 was -1.43 log in the enfuvirtide arm and -0.65 log in the control arm. Forty-three percent of participants achieved a 1 log reduction in the enfuvirtide arm versus 21% in the control arm. Viral load below 400 and 50 copies/ml, respectively, was achieved by 28.4% and 12.2% of the enfuvirtide arm compared to 12.2% and 5.3% of the control arm.
Enfuvirtide is self-administered by subcutaneous injection. Dr J. Green reported at the conference that about 85-90% of enfuvirtide recipients do not find the process of self-administration difficult.
Most people injecting enfuvirtide report some pain or discomfort at the injection site. In a majority of cases, this pain is deemed to be mild or moderate. Less than 10% of recipients in the two TORO studies had to take painkillers to ease injection site pain. About 3% ceased treatment with enfuvirtide due to injection site reaction. No other side-effects were reported as being significantly associated with enfuvirtide.
Enfuvirtide appears to be a particularly appealing salvage option as it is not affected by resistance to the existing antiretroviral agents. Available evidence suggests that 97% of viral envelopes will be sensitive to enfuvirtide (Greenberg).
Developed by Trimeris and Roche, enfuvirtide is currently an experimental treatment with limited availability.
Clotet B et al. Enfuvirtide (T-20) in combination with an optimized background (OB) regimen vs. OB alone in patients with prior experience or resistance to each of the three classes of approved antiretrovirals in Europe and Australia (TORO 2). XIV International AIDS Conference, Barcelona, abstract LbOr19A, 2002.
Green J et al. Patient survey on injection of enfuvirtide (T-20): ease of use and impact on activities. XIV International AIDS Conference, Barcelona, abstract TuPeB4480, 2002.
Greenberg M et al. Fusion inhibitors. XIV International AIDS Conference, Barcelona, MoOrA139, 2002.
Henry K et al. Enfuvirtide (T-20) in combination with an optimized background (OB) regimen vs. OB alone in patients with prior experience or resistance to each of the three classes of approved antiretrovirals in North America and Brazil (TORO 1). XIV International AIDS Conference, Barcelona, abstract LbOr19B, 2002.