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Session 125 Poster Abstracts
Pregnant Women and Children: Immunology
Wednesday, 1:30 - 3:30 pm
Poster Hall


916    
Lymphoproliferative and Serological Responses to Recall and Neoantigens in Severely Immunocompromised HIV-infected Children Initiating HAART: 48-Week Follow-up
M Rigaud*1, W Borkowsky1, A Weinberg2, P LaRussa3, P Muresan4, T Fenton4, S Jankelevich5, J Read6, E Ferguson7, D Smith8, B Zimmer9, and representing the P1006 Team of the PACTG
1New York Univ. Sch. of Med., NY, USA; 2Univ. of Colorado Hlth. Sci. Ctr., Denver, USA; 3Columbia Presbyterian Med. Ctr., New York, NY, USA; 4Harvard Sch. of Publ. Hlth., Boston, MA, USA; 5NIAID, NIH, DHHS, Bethesda, MD, USA; 6NICHD, NIH, DHHS, Bethesda, MD, USA; 7NIAID/PAB, NIH, DHHS, Bethesda, MD, USA; 8Univ. of Massachusetts Hlth. Care, Worcester, USA; and 9Frontier Sci. and Technology Res. Fndn., Amherst, NY, USA

Background:  HIV-infected children with advanced disease tend to have high viral loads and low CD4 counts.  It has been shown that treatment with HAART suppresses HIV viremia and significantly increases CD4%. The breadth of immune restoration, however, continues to be an area of active research.  P1006 is assessing the LP and SR responses after vaccination with recall and neoantigens.

Methods:  In this ongoing, prospective study of severely immunosuppressed (CD4%<15), children who initiate HAART and who demonstrate a decrease of >0.75 log in plasma HIV RNA copy number within 4 weeks ("virologic responders") are randomized to receive tetanus toxoid (TT) [GrpI], representative of a recall antigen, or hepatitis A vaccine [GrpII], representative of a neoantigen, at 8, 16, and 24 weeks after starting therapy. Subjects then are vaccinated with the other vaccine at weeks 32, 40, and 48. Antigen-specific responses to tetanus and hepatitis A are measured by lymphoproliferative (LP) assays performed after vaccinations. A positive LP response is defined as a stimulation index of > 3.  Serological responses (SR) to tetanus and to hepatitis A are measured by ELISA. A serological value of  >0.1 IU/mL corresponds to a positive response for tetanus and a level of >10 IU/mL for hepatitis A. CD4% and HIV plasma RNA at times of immunization are correlated with immune responses.

Results:  Of 53 virological responders, 32 received vaccines. The 2 groups were similar at baseline:  age (median 11 years), CD4% [(median 8 (GrpI) and 6 (Grp II)] and log RNA [(5.10 (GrpI) and 4.7 (GrpII)]. Overall, CD4% increased from 7 ( baseline) to 15 (24 weeks) and 17 (48 weeks). HIV log RNA decreased from 5 (baseline) to 2.6 (24 weeks) and 2.8 (48 weeks). LP responses to tetanus were seen in 63% and 64% in GrpI and GrpII, respectively. LP responses to hepatitis A were seen in 14% and 23% in GrpI and GrpII, respectively. Serologic responses to tetanus were seen in both groups after 3 immunizations with TT.  Antibody responses to hepatitis A were seen more often than LP responses but were of very low titer.

Conclusions:  Severely immunosuppressed children and adolescents on HAART  with some suppression of HIV viremia and increased CD4% have limited LP response to recall and neoantigens. SR response to neoantigens also appears attenuated. Although limited by the relatively small number of subjects in each group, there is no evidence of difference in LP and SR response between the 2 groups.

Keywords: immunoreconstitution; pediatric; vaccine