Top Ten Research Reports of 2003
9. Enfuvirtide, an HIV-1 Fusion Inhibitor, for Drug-Resistant HIV Infection in North and South America
Lalezari J.P., Henry K., O'Hearn M. et al. Enfuvirtide, an HIV-1 Fusion Inhibitor, for Drug-Resistant HIV Infection in North and South America.
New England Journal of Medicine. 2003 May 29; 348(22):2175-85.
Lazzarin A., Clotet B., Cooper D. et al. Efficacy of Enfuvirtide in Patients Infected With Drug-Resistant HIV-1 in Europe and Australia. New England Journal of Medicine. 2003 May 29; 348(22):2186-95.
Any clinician who has received a genotype with more red ink on it than any other color is well aware that there is a need for the HIV drug pipeline to keep pumping. One of the best hopes to come along for patients with highly resistant HIV is enfuvirtide (T-20, Fuzeon). Certainly, there are problems with this first approved drug of the fusion inhibitor class -- including limited access, twice-a-day injections, injection site reactions, cost -- but enfuvirtide is a powerful agent that has given many patients a second (well, for many people, its more like a third, fourth or fifth) chance. The efficacy and safety of this agent in treatment-experienced patients was examined in two similar studies known as TORO1 and TORO2, which were published in the New England Journal of Medicine.
What Is New Here?
These are the first controlled studies of enfuvirtide. Together, they enrolled more than 1,000 subjects with triple-antiretroviral-class experience and/or resistance to agents in each of these classes and a viral load above 5,000 copies/mL. Two thirds of the subjects were randomized to optimize their therapy and add enfuvirtide; the remaining third optimized therapy without the addition of enfuvirtide.
After six months, the average decrease in the HIV-1 RNA level was 1.7 and 1.4 copies/mL in the TORO1 and TORO2 enfuvirtide groups, respectively, versus a drop of 0.8 and 0.6 log10 copies/mL in the control groups. The percentage of patients with an HIV-1 RNA level below 50 copies/mL and the percentage with a decrease of more than 1.0 log10 copies/mL were both significantly greater in the enfuvirtide arms than in the control groups. Not surprisingly, CD4 cell counts increased more among those on enfuvirtide.
Enfuvirtide is not without toxicity. Injection site reactions are inevitable and are characterized by painful nodules that can persist. Tellingly, however, few subjects discontinued therapy because of injection site reactions (<3%). Massaging the site after the injection and applying ice when reactions develop can help. For unknown reasons, pneumonia was experienced in the subjects receiving enfuvirtide at a rate eight times that seen in the controls. In addition, two patients had a serious, systemic hypersensitivity reaction to enfuvirtide, which on re-challenge, reoccurred.
The Bottom Line
Enfuvirtide is a potent new agent that can benefit some of the patients who need the most help in controlling their virus. This potential is hindered by the requirement for twice-daily injections. Looming even larger is the cost of the drug, currently around $20,000 annually. This is an incredible sum that, when coupled with the other medications candidate patients are taking, exceeds $30,000 a year. (The recent increase in the price of ritonavir pushes this figure even higher.) Also, the supply of the drug has been limited due to manufacturing issues.
For patients with access to it, enfuvirtide is an excellent rescue option for a motivated patient. Its role will likely expand if access improves, familiarity with the drug grows and its price enters the realm of reason.
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