Safety and antiretroviral activity of chronic subcutaneous administration of T-20 in human immunodeficiency virus 1-infected children

Background. Entry inhibitors, a new class of antiretroviral agents, interfere with the attachment, coreceptor interaction or fusion of HIV-1 with host target cells. The fusion inhibitor T-20 is the first in this new class, and the present study is the first to examine chronic sc administration of T-20 to HIV-1-infected children. Methods. Fourteen children, 4 to 12 years of age, with incompletely suppressed HIV-1 were studied. The median plasma viral load at baseline was 26 866 copies/ml (4.4 log 10 ), and the median CD4 count was 523 cells/mm 3 . T-20 was administered twice daily by sc injection at 30 or 60 mg per m 2 of body surface area per dose. For 7 days T-20 was added to the patients' background antiretroviral regimens; at Day 7 each subject's background therapy was changed to a regimen that was predicted to be virologically active, while T-20 was continued. Results are presented for the first 24 weeks of chronic T-20 dosing. Results. T-20 was generally well-tolerated. One child discontinued the drug because of aversion to injections, but no child discontinued because of adverse events. Eleven (79%) of 14 children had local injection site reactions at some time during the chronic T-20 dosing. Eleven of 14 subjects achieved the protocol-specified milestone of at least a 0.7-log 10 reduction in plasma HIV-1 RNA by Day 7. In 10 subjects (71%) virologic suppression of 1.0 log 10 or greater was achieved at 24 weeks; 6 subjects (43%) had viral loads