12th CROI Abstract #752

Session 130 Poster Abstracts
T-Cell Responses in Children
Wednesday, 1:30 - 3:30 pm
Hall B

752

Volumetric computed tomography of the Thymus and Parameters of Thymopoiesis in Adolescent and Adult Survivors of Perinatal HIV Infection
Krogstad Paul*¹, J Church², M Belzer², J Deville¹, K Nielsen¹, C Kitchen³, J Lee¹, S Weston¹, Y Geng¹, and M Boechat¹
¹Geffen Sch of Med, Univ of California, Los Angeles Med Ctr, USA; ²Childrens Hosp and Keck Sch of Med at Univ of Southern California, Los Angeles, USA; and ³Univ of California, Los Angeles, Sch of Publ Hlth, USA

Background: Prior to 1996, potent ART was unavailable to children with perinatal infection. We hypothesized that unchecked HIV replication in early childhood may have lead to disruption of the thymic architecture that cannot be fully reversed by therapy. We therefore examined computed tomography (CT)-rendered thymic volume and parameters of thymopoiesis in clinically stable adolescents and young adults with HIV infection that was acquired perinatally, or by neonatal transfusion. Seronegative young adults served as controls for this analysis.

Methods: We enrolled 25 adolescents and adults with HIV infection acquired perinatally (n = 21) or by transfusion in infancy (n = 4); 15 (60%) had CDC class C disease. All were receiving HAART; 5 had plasma HIV RNA levels between 400 and 7500 copies/mL; and 20 had a viral load < 400 copies/mL for at least 1 year. Non-contrast CT of the thorax using 3-mm collimation was obtained, with volumetric analysis subsequently performed on a 3D imaging workstation. Whole blood antibody staining and flow cytometry were used to quantify CD4, CD8, and naļve CD45RA⁺CD27⁺CD4⁺ T-cell populations. T-cell receptor recombination excision circles (TREC) in total PBMC were quantified by real time PCR.

Results: The HIV-infected subjects (n = 25) were slightly younger than control subjects (n = 16) (mean age 18 [SD 1.4] vs 20 years [SD 1.4], p = 0.0015) but had very similar thymus volume (20.2 [SD 13.1] vs 15.4 [SD 6.09] mL (p = ns). CD4⁺ T-cell number and percentage were higher in the seronegative group (37.8%, 694 cells/µL vs 25.3%, 552 cells/µL), but the perinatally infected youths had mean TREC and naļve CD4⁺ T-cells values that were statistically indistinguishable from the control group. The number and percentage of total and naļve CD4 T-lymphocytes were highly correlated with thymic volume in the control group. In the HIV⁺ youth, TREC concentrations were strongly correlated with the volume of the thymus (r = 0.62, p = 0.018).

Conclusions: Despite lifelong HIV infection, perinatally infected youth with successful and sustained ART may reach adulthood with essentially normal parameters of thymopoiesis.

Keywords: Perinatal infection; thymopoiesis; adolescent