684   Virologic and Immunologic Responses in Children with Advanced HIV Disease on a New HAART Regimen (PACTG 366).

A. Kovacs*¹, S. Burchett², M. Khoury¹, V.Carey³, S. Pahwa⁴, K. McIntosh², R. Oyomopito³, E. Smith⁵, L. Mofenson⁵, and the PACTG 366 Team.
¹USC Sch. of Med., Los Angeles CA^;2Boston Children's Hosp., Boston, MA;³Harvard Sch. of Publ. Health, Boston MA;⁴North Shore Univ. Hosp., Manhasset, NY; and⁵NIH, Bethesda, MD.

Background:The objective of this study was to evaluate virologic and immunologic responses following ART change among protease inhibitor- (PI) and NNRTI-naïve and -experienced children and adolescents ages 6 mo to 20 yrs with advanced HIV disease.

Methods:Subjects (n = 201) with >50,000 RNA copies/ml, %CD4 <15, growth failure or CNS disease began 4 drug HAART regimens such that all prior agents were changed and >1were novel. Viral load response (VLR: reduction >0.75 log₁₀was assessed at 12/16 (primary VLR) and 48 wks (durable VLR) from baseline. Complete VLR was defined as <400 copies/ml. Immunologic response was defined as an 8% increase in %CD4. All analyses were intent-to-treat.

Results:Compared to PI-experienced pts, PI-naive pts were more likely to have primary VLR (66% vs. 43%, p < 0.01) and durable VLR (47% vs. 21.4%, p < 0.01). Complete VLR was also seen more often in PI-naive vs. PI- experienced pts at 12/16 (49% vs. 18%) and 48 wks (37% vs. 7%). Controlling for prior ART, subjects with higher baseline %CD4 had a greater probability of VLR (p < 0.01); while those with higher baseline %CD8, %activated -CD4 or -CD8 were less likely to have VLR (p = 0.03, 0.02, and 0.01, respectively). Controlling for 0.01).

Conclusions:In these highly ART-experienced children and adolescents, primary VLR could be achieved in the majority, yet durability of response was associated with lack of prior PI therapy. New initiation of PIs affords the best opportunity for both VLR and CD4 response.