By Liz Highleyman

Raltegravir, the first and so far only approved integrase inhibitor, has demonstrated good anti-HIV activity in both treatment-experienced and treatment-naive adults, and to date has been associated with remarkably minimal side effects.

Investigators with the IMPAACT P1066 study team analyzed the safety and antiretroviral efficacy of raltegravir in pediatric HIV patients aged 12-18 years. The ICAAC presentation included data from Stage 1 (dose-finding, pharmacokinetics, and safety) and Stage 2 (extended follow-up).

The study enrolled 69 participants; 24-week efficacy data was available for 55 patients. Participants were roughly evenly divided between boys and girls. The median age was 15 years, about 60% were black, the median baseline CD4 cell count was about 400 cells/mm3, and the CD4 percentage was 20%. None had taken integrase inhibitors before. Patients with hepatitis B or C coinfection were excluded.

Based on Stage 1 dose-finding data, a dose of 400 mg twice-daily was selected; patients who did not initially receive this dose switched to it for ongoing follow-up.

Results

	In an intent-to-treat analysis at 24 weeks, 53% of participants achieved HIV RNA < 50 copies/mL (Stage 1 and 2 combined; 55 patients).
	71% achieved virological "success," defined as HIV RNA < 400 copies/mL or at a least a 1 log drop from baseline.
	The median CD4 cell gain was 111 cells/mm3.
	Among the 69 total participants, raltegravir was described as "very well tolerated."
	No patients discontinued the study drug due to toxicities.
	4 patients experienced grade 3 or higher toxicities considered possibly related to raltegravir (2 with neutropenia, 1 with elevated GGT liver enzymes, 1 with behavioral changes).

Based on these findings, the researchers concluded that, "In HIV-infected youth ages 12-18, raltegravir appears generally safe and well tolerated through week 24, and achieved efficacy rates comparable to those in treatment-experienced adults."

Univ. of Washington and Seattle Children's Hospital, Seattle, WA; SUNY, Stony Brook, NY; Harvard School of Public Health, Boston, MA; Univ. of Alabama, Birmingham, AL; Merck, North Wales, PA; NIAID, Bethesda, MD; NICHD, Bethesda, MD; Frontier Science, Inc., Buffalo, NY; Jacobi Medical Ctr., Bronx, NY.

9/29/09

Reference
S Nachman, P Samson, L Frenkel, and others. 24 Week Safety and Efficacy from IMPAACT P1066: A Phase I/II, Multicenter, Open-Label, Noncomparative Study to Evaluate Raltegravir (RAL) in HIV-1 Infected Youth. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009). San Francisco. September 12-15, 2009. Abstract H-924a.