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Background:  T20-310 is an ongoing phase I/II pharmacokinetic, safety and efficacy study of enfuvirtide (ENF) in combination with an optimized background in HIV-infected children and adolescents.

Methods:  ENF was administered subcutaneously at a dose of 2 mg/kg twice daily (maximum 90 mg/dose) in addition to an optimized background ART regimen to heavily pretreated HIV-1-infected children (5 to 11 years) with HIV-1 RNA ≥ 5000 copies/mL. Assessments for efficacy (HIV-1 RNA, CD4 counts) and safety parameters, including evaluations of injection site reactions, were performed monthly through week 24 and bimonthly thereafter. Primary 24-week safety and efficacy results in children are presented. Data from adolescents (12 to 16 years) were presented previously.

Results:  We enrolled 24 children (63% female; median age 9 years) with a median baseline HIV-1 RNA of 4.9 log₁₀ copies/mL and CD4 count of 371 cells/µL. Median number of previous ART was 10 and mean number of ART in the optimized background was 3.4. Based on genotype testing, viral isolates from 23 (96%) patients were sensitive to ≤ 3 ART in the patient’s optimized background at baseline, from 2 (8%) to only 1 ART, and to no ART in 8 (33%); 21 (88%) patients remained on therapy at week 24. One patient who discontinued due to multi-organ failure and metabolic disorder subsequently died, but the death was considered unrelated to ENF; 2 patients refused treatment. At week 24, median changes from baseline HIV-1 RNA and CD4 cell count were –1.53 log₁₀ copies/mL and +182 cells/µL, respectively (on treatment); 33% had a viral load of < 400 copies/mL; 5 patients reported severe adverse effects (1 for pneumonia), none of which were considered by the investigator to be related to ENF. Injection site reactions were reported by most patients (88%) and, of these, the worst grade reported was mild or moderate in 57%. The most frequent injection site reaction signs and symptoms were induration (75%), nodules and cysts (58%) and erythema (50%). Other events commonly reported were upper respiratory infection (n = 10, 42%), nasopharyngitis (n = 5, 21%), pyrexia (n = 5, 21%), vomiting (n = 5, 21%), otitis media, and loose stools (each in 4 patients, 17%). All of these events except 1 case each of upper respiratory infection and pyrexia were considered unrelated to ENF.

Conclusions:  ENF is well tolerated and generally safe in heavily pretreated HIV-1-infected children. ENF also provided potent antiviral activity and associated immunological reconstitution in this patient population.

Keywords: enfuvirtide; fusion inhibitor; pediatric