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Session 105 Poster Session Pediatric HIV Infection: Disease Progression and Responses to Therapy Session Time: 4:30-6:30 pm Room 4E-F

812-W. HIV-1 Evolution during Effective HAART L. M. Frenkel, Y. Wang*, J. McKernan, A. J. Melvin, S. DeVange, G. M. Ellis, K. M. Mohan, G. L. Sylva, L. Heath, M. Mahalanabis, W. E. Naugler, I. A. Beck, P. Lewis, G. H. Learn, and J. Mullins Univ. of Washington, Seattle and Oregon Health Sci. Univ., Portland Background: Genetic studies were conducted to gain insight into selection of drug-resistant HIV-1 during apparently effective HAART. Methods: HIV-1 was sampled from PBMC at intervals before and during HAART that suppressed plasma HIV-1 RNA to below the limit of detection. 10 or more pol and env amplicons were sequenced directly from dilutions of PBMC with a high probability of having only one HIV-1 template. Analyses included phylogenetic relationships, distances from the inferred Most Common Recent Ancestor sequence and changes in the frequency of drug-resistance mutations. Results: 10 children were studied before and during effective HAART that included protease inhibitors, over a median of 4.3 years. 7 of 10 were initially prescribed a 3-drug regimen. 2 of these had detectable evolution in their phylograms, 5 had selection of drug-resistance mutations, and 4 had rebound of plasma HIV-1 RNA to >500 copies/mL. 4- or 5-drug HAART was studied in 8 children. No evolution was detected in 7 of the 8 by phylogenetic analysis. One continued to show selection of drug-resistance mutations following intensification from 3 drugs, however, his plasma viral load was maintained at a median of <50 (range <50-101) copies/mL throughout 4 years on a 5-drug regimen. Among the others, viral replication was implied by selection of drug-resistance mutants in 1, and persistence of pre-existing drug-resistance mutations in an additional 3. Viral rebound (>500 copies/mL) was not observed during 4- or 5-drug HAART. HIV-1 PBMC DNA levels decreased by >1 log in 3 of the 10 children, and these had little or no evidence of viral replication. Conclusions: Evidence of continuing HIV-1 replication can be found in most children during successful HAART, even when HIV-1 plasma RNA is <50 copies/mL. Increases in the frequency of specific drug-resistance mutations over time was a more sensitive indicator of ongoing viral replication than phylogenetic analysis. Evidence for viral replication was less during treatment with combinations of 4 or 5 drugs compared to 3-drug HAART. Importantly, minimal evidence of viral replication was associated with a significant drop in PBMC viral load after starting HAART.

©2002 9th Conference on Retroviruses and Opportunistic Infections