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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

806-W. Rapid Progression of HIV-1 Infection in Infants Associated with CCR5 and not CXCR4 Co-Receptor Usage A. Ashraf1, S. Beddows1, H. Lyall2, M. McClure1, G. Taylor*1, and 2 1Imperial Coll. and 2St. Mary's Hosp. NHS Trust, London, UK Background: The mean time from infection to first AIDS-defining illness in adults is 10 years but 20% of children infected through materno-fetal transmission present with AIDS or die within the first year of life. CXCR4 co-receptor using viruses are associated with later stages of infection and more advanced disease in adults and children. Selection for CXCR4 viruses by passage across trophoblasts has been reported in vitro. We investigated co-receptor usage in children presenting with symptomatic HIV infection in the first year of life. Methods: HIV-1 was isolated from cryopreserved peripheral blood mononuclear cells from 14 infants by co-cultivation with negatively selected, phytohaemagglutinin-activated CD4+ lymphocytes. HIV-1 co-receptor usage was determined by 4-5 days culture of U87-CD4 cells stably expressing the chemokine receptors CCR1, CCR3, CCR5 or CXCR4 with 128-1089 tissue culture infectious doses of each primary isolate. Infection was detected by focal immunoassay. A 1.2-kb fragment of env was amplified from DNA extracted from PBMCs prior to and following amplification and sequenced. Assignment of the speculative biological phenotype was made according to the charge of amino acid residues at positions 11 and 25 in V3. Results: Co-receptor usage was identified for 11 of the 14 viral isolates. 4 of the children have died, the remainder are on combination antiretroviral therapy. The children were all infected with non-B clade viruses which utilised the CCR5 co-receptor. Conclusions These data are consistant with the view that the placenta is an efficient barrier to HIV-1 transmission. Transmission of maternal viruses, which are likely to use CCR5, may occur when the barrier is breached or by-passed. The rapid advance of HIV infection in these infants was not due to CXCR4 co-receptor usage. Should compounds which block CCR5 co-receptors become clinically useful and not select for virus which uses CXCR4 these data suggest that they might also be useful to prevent mother-infant transmission and for the treatment of infected infants.

©2002 9th Conference on Retroviruses and Opportunistic Infections