Enfuvirtide antiretroviral therapy in HIV-1 infection

Christina MR Kitchen¹, Miriam Nuño¹, Scott G Kitchen², Paul Krogstad³

¹Department of Biostatistics, UCLA School of Public Health, Los Angeles, CA USA; ²Department of Hematology and Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA USA; ³Departments of Pediatrics and Medical Molecular Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

Abstract: It has been over 25 years since the first diagnosis of what would be known as AIDS. Although great strides in anti-HIV therapeutics have been made, there is still a great need for antiretrovirals that are effective against drug-resistant HIV. Enfuvirtide (ENF) is the first of a new class of fusion inhibitors to be approved by the US Food and Drug Administration for use in combination with other antiretroviral agents among HIV-1 infected patients with previous treatment experience. The inclusion of enfuvirtide in an optimized antiretroviral background regimen for the treatment of HIV-1 infected (treatment-experienced) patients followed the success of two critical clinical trials (TORO: T20 vs Optimized Regimen Only I and II). Even though injection-site reactions persisted in these trials, improved virological and immunological responses were observed among patients. Challenges associated with ENF treatment include the high cost of the drug, injection-site reactions, determining the optimal time to initiate treatment, and the potential for the selection of drug resistant mutants and viral evolution. ENF is a promising novel treatment for HIV infected individuals whose choices for effective treatment are limited by previous treatment and resistance. Understanding the implications of viral fitness and evolution in the presence of ENF treatment is crucial in determining effective and safe treatment regimens, particularly among treatment-experienced patients.

Keywords: enfuvirtide, HIV, salvage therapy, drug resistance, gp41, evolution