Background:
Results from the TORO studies through 24 weeks described the safety and
efficacy of the HIV-1 Fusion Inhibitor enfuvirtide (ENF) + optimized
background ARVs (OB) to OB alone. The following are results through 48 weeks
of treatment.
Methods:
Patients with >3 months experience with 3 classes of ARVs, and
HIV-1 RNA >5,000 copies/mL selected an OB regimen of 3–5 ARVs based
on prior history and baseline (BL) resistance testing. Patients were
randomized 2:1 to ENF (90 mg SC BID) + OB or OB alone. Based on differential
exposure to ENF+OB and OB [557 vs 162 patient-years (PY), respectively],
safety data were adjusted by exposure (events per 100 PY of exposure).
Results:
The ITT population included 661 patients on ENF+OB and 334 on OB who
were randomized, treated, and had at least one post-BL viral load
assessment. Median BL HIV-1 RNA and CD4+ cell count were 5.1 log10 copies/mL
and 92 cells/mm3, respectively. On average patients had prior exposure to 12
ARVs. At 48 weeks the mean adjusted change from BL in HIV RNA and CD4+ cells
in the ENF+OB and OB groups (ITT, LOCF) was –1.48 vs –0.63 log10 and 91 vs
45 cells/mm3 respectively (both p<0.0001). 37.4% of patients on ENF+OB had
>1 log decrease from BL in viral load (vs 17.1% on OB) 30.4% had <400
copies/mL (vs 12.0% on OB), and 18.3% had <50 copies/mL (vs 7.8% on OB; all
comparisons ENF+OB vs OB, p<0.0001). Local injection site reactions resulted
in discontinuation in 4.4% of patients. The rate of bacterial pneumonia in
patients treated with ENF+OB and OB was 6.6 vs 0.6 events per 100 PY,
respectively. Exposure-adjusted rates of other AEs were generally comparable
between treatments.
Conclusion:
These data support the efficacy and safety of ENF+OB over OB through 48
weeks of treatment and substantiate the utility, tolerability and
feasibility of long-term ENF therapy.
