Patients will have options regarding T-20 (enfuvirtide) injection sites

T-20 (Enfuvirtide) is likely to be the first of the “entry inhibitors” to be approved. This new class of antiretroviral drugs suppresses HIV replication by blocking one of a series of steps required for it to gain entry into the human cell. While other entry inhibitors block certain surface receptors, T-20 blocks gp41-mediated viral fusion to host cells.

The good news regarding enfuvirtide is that it has been shown in several studies, including two important studies presented at the XIV International AIDS Conference (TORO-1 and TORO-2), to significantly increase viral suppression and improve CD4+ T cell counts in HIV-infected patients on salvage antiretroviral therapy, i.e., patients that have failed multiple regimens and have limited further therapeutic choices.

The bad news regarding T-20 is that it must be injected subcutaneously (SC) twice daily. Further, while studies have shown that it is preferentially injected in the abdominal area, where there is very good absorption, T-20 absorption is complex and there has been concern that the location of the injection site may significantly impact its bioavailability. This could cause problems for patients since T-20 frequently causes a local site reaction, which may persist for days, and the ability to rotate sites may be extremely important.

In a study presented at the Barcelona AIDS conference, T-20 absorption was studied in a multiple dose, three-way randomised, crossover study. The study involved 12 HIV-1infected patients who received 90 mg doses of T-20 twice daily at three different injection sites located either in the abdomen, thigh or arm, in three consecutive periods of seven days each. Serial blood samples were collected and levels of plasma T-20 and its metabolite concentrations were measured.

The investigators found that compared to the abdomen, absorption of T-20 in the thigh is comparable and in the arm is slightly better. Compared to the abdomen, the relative bioavailability of T-20 in the thigh is virtually the same (AUC12h 101%) and in the arm it is somewhat, but not significantly, higher (AUC12h 117%). Further, plasma concentrations of the T-20 metabolite were approximately 15% of the parent drug regardless of the site of injections, and the metabolite represents only “a minor constituent in plasma”.

Based upon these data, the authors conclude, “Because of comparability in absorption of T-20 from the three different SC injection sites, T-20 offers HIV-1 infected patients the freedom to rotate the site of injection.”

IH Patel , J Lalezari2, A Dorr et al. T-20 is optimally absorbed from 3 different subcutaneous injection sites. XIV International AIDS Conference. July 7-12, 2002. Barcelona, Spain. Abstract TuPeB4542.