Church JA, Cunningham C, Hughes M, et al. Pediatr Infect Dis J. 2002;21:653–659
Purpose of the Study.
The use of combination antiretroviral therapy has been associated with a substantial decline in morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. In heavily pretreated subjects, however, the virus often possesses multiple mutations of the reverse transcriptase and protease genes that result in multidrug resistance. Pharmacologic agents effective at alternative stages in the replication cycle of the virus might be useful. The purpose of this study is to evaluate the use of T-20, an inhibitor of virus entry into the target cell, in HIV-infected children.
Fourteen children, 4 to 12 years of age, with incompletely suppressed HIV were studied. T-20 was administered twice daily by subcutaneous injection. For the first 7 days of the study T-20 was added to the patients’ background antiretroviral therapy, and at day 7 each subject’s failing background therapy was changed to a regimen that was predicted to be virologically active while the T-20 was continued.
T-20 was generally well-tolerated. One child discontinued the drug because of aversion to injections, but no child discontinued because of adverse events. Seventy-nine percent of the children had local injection site reactions at some time during chronic T-20 dosing. Eleven of 14 subjects achieved the protocol-specified milestone of at least 0.7 log reduction in plasma HIV RNA by day seven. Seventy-one percent of subjects had virologic suppression of 1 log or greater by 26 weeks.
A 24-week regimen of twice daily subcutaneous dosing of T-20 in HIV-infected children is safe and tolerable and it is associated with suppression of HIV replication during 24 weeks of administration.
Because HIV-infected children often develop resistance to 1 or more classes of antiretroviral therapy, a new class of agents might improve treatment options. Although T-20 administration required twice-daily injections, this should not prevent children from having access to this agent. Treatments requiring daily injections are routinely used in the management of other serious pediatric conditions, and in this study, 13 of 14 subjects enrolled in chronic dosing continued participation throughout the study. In carefully selected and vigorously supported families, T-20 was a tolerable component of an infective antiretroviral combination for HIV-infected children.