Immunologic Responses during Antiretroviral Therapy in Pediatric HIV-1 Disease
Session Day and Time: Thursday 1:30 - 3:30 pm
Room: Hall B
Background: Structured Treatment Interruption (STI) in adults acutely infected with HIV induces HIV-specific responses mediated by CD4+ and CD8+ cells that may enhance control of viremia. The effect of STI in children is not known.
Methods: In this ongoing, prospective study, 7 children with chronic HIV infection on HAART with plasma virus < 50cp/ml have undergone sequentially lengthening periods of STI (beginning at 3 days), followed by 28–84 days of HAART if virus exceeds 50cp/ml. HIV-specific responses are assessed by interferon-γ ELISpot. PBMC are stimulated with zinc-finger inactivated whole HIV (WHIV) or recombinant HIV/vaccinia vectors (HIV/vv) expressing gag, env, pol, or nef, or controls. The number of HIV-specific spot-forming cells (SFC)/106 PBMC is determined. Lymphoproliferation (LP) is determined in PBMC stimulated 6 days with WHIV or control and harvested after pulsing with 3H-thymidine. A stimulation index (SI ≥ 3) defines a positive response.
Results: Baseline median SFC was 26, 3, 3, 13, and 0 for WHIV, gag, env, pol, and nef, respectively. The median change from baseline in ELISpot after the 2nd STI during which plasma virus was > 50cp/ml was 83, 15, 23, 78, and 25 for WHIV, gag, env, pol, and nef, respectively (n = 6,6,6,6,5). The fraction of subjects with a 4-fold or more increase from baseline in ELISpot was 3/6, 4/6, 3/6, 3/6, and 1/5 for WHIV, gag, env, pol, and nef, with increases ranging from 4- to 35-fold. All 6 subjects had increases of 4-fold or more to at least one HIV/vv. Subjects (n = 2) who have undergone 4 STI with virus > 50cp/ml had a median increase in ELISpot of 239, 93, 651, and 452 for WHIV, gag, env, and pol (nef not tested). Following their latest STI, 4 of 7 subjects have > 100 SFC to 1 or 2 HIV/vv to which their baseline responses was < 30 SFC. LP responses to WHIV were positive in 2/7, 2/6, and 2/2 of subjects at baseline, after the 2nd and after the 4th STI with detectable virus, respectively.
Conclusions: These data suggest that STI during established HIV infection in children increases the frequency and antigenic breadth of HIV-specific CD4+ and CD8+ cell responses.