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 s.c. 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 log10), and the median CD4 count was 523 cells/mm3. T-20 was administered twice daily by s.c. injection at 30 or 60 mg per m2 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-log10 reduction in plasma HIV-1 RNA by Day 7. In 10 subjects (71%) virologic suppression of 1.0 log10 or greater was achieved at 24 weeks; 6 subjects (43%) had viral loads <400 copies/ml and 3 (21%) had fewer than 50 copies/ml at 24 weeks.


CONCLUSIONS
These results indicate that a 24-week regimen of twice daily s.c. dosing of T-20 in HIV-1-infected children is safe and tolerable and that it is associated with suppression of HIV-1 replication during 24 weeks of administration.
Church
Joseph A
JA
Department of Pediatrics, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, 90027, USA. jchurch@chla.usc.edu
Cunningham
Coleen
C
Hughes
Michael
M
Palumbo
Paul
P
Mofenson
Lynne M
LM
Delora
Patricia
P
Smith
Elizabeth
E
Wiznia
Andrew
A
Purdue
Lynette
L
Hawkins
Elizabeth
E
Sista
Prakash
P
D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006801:Humans; D007279:Injections, Subcutaneous; D008134:Long-Term Care; D008297:Male; D020714:Maximum Tolerated Dose; D011336:Probability; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016037:Single-Blind Method; D015996:Survival Rate; D016896:Treatment Outcome; D019562:Viral Load
D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase