496-M. Autologous Neutralizing Antibody (ANAB) to Concurrent and CD4 T-Cell-Recovered Virus in HIV Infected Children on HAART

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Session 69 Poster Session
Immunopathogenesis Issues Addressed by Therapeutic Interventions
Session Time: 4:30-6:30 pm
Room 4E-F

496-M.

Autologous Neutralizing Antibody (ANAB) to Concurrent and CD4 T-Cell-Recovered Virus in HIV Infected Children on HAART
N. Ching*¹, L. Wei¹, J. Deville¹, K. Nielsen¹, S. Wolinsky², and Y. Bryson¹
¹Univ. of California, Los Angeles and ²Northwestern Univ., Chicago, IL

Background: A patient’s ability to produce NAB to current and past HIV isolates may be correlated with reduced disease progression and protection against maternal fetal transmission. Little is known about the effect of prolonged viral suppression by HAART on the NAB response in HIV infected infants and children. We assessed ANAB to pre-HAART isolates and post-HAART virus recovered from latent CD4 T-cell reservoirs.
Methods: ANAB assays were performed pre and post HAART in perinatally infected children using a PBMC-based assay. Pre-treatment virus was isolated from PBMCs. Post HAART viral isolates were recovered from CD4 T-cell reservoirs by previously described methods. NAB titers are expressed as the reciprocal dilution producing 90% neutralization compared to virus controls.
Results: We studied 3 HIV-infected children ages 3.5, 7.25, and 6.5 years and 2 infants ages 3 months and 1 day prior to HAART (mean entry plasma virus HIV RNA=408,073 copies/mL). All children were clinically stable and responded with viral suppression <50 HIV RNA copies/mL for >36 month and an increase in mean CD4 T cells (36%) (p<0.05). At baseline, 4/5 children had detectable NAB_90% titers to concurrent virus isolates (80, 80, 1280, <20 and 640). Follow-up at 9-48 months post HAART showed NAB_90% titers against original HIV isolates (40, 1280, 40, 160, and 20 respectively). In 4/5 children with plasma HIV RNA <50 copies/mL, CCR5 tropic HIV isolates were recovered from CD4 T cell reservoirs 13-51 months post HAART. 3 of these children neutralized the concurrent reservoir virus (NAB_90% titers 1280, 80, & 80). Interestingly, 2 of them also neutralized the post HAART reservoir virus with baseline plasma (NAB_90% titers 1280 and 160). 1 infant treated early with HAART had no NAB to current or past isolates at 9 months of age.
Conclusions: HIV-infected children had significant NAB_90% titers against concurrent HIV isolates prior to HAART. Although NAB response varied post-HAART, only 1 infant with early treatment had no detectable NAB. Interestingly, most children had NAB against concurrent virus from CD4 T-cell reservoirs. The observation of baseline NAB activity against a later recovered virus suggests that the “latent” reservoir may be established early in life prior to HAART.