504-M. Impaired Responses to Immunization in HIV-Infection despite CD4+ T-Cell Restoration after Suppressive Antiretroviral Therapy

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

504-M.

Impaired Responses to Immunization in HIV-Infection despite CD4+ T-Cell Restoration after Suppressive Antiretroviral Therapy
C. Lange*^1,3, H. Valdez¹, K. Medvik¹, R. Asaad¹, M. Wild², R. Kalayjian²,, and M. Lederman¹
¹Univ. Hosp. and ²Metrohealth Hosp., Case Western Reserve Univ., Ctr. for AIDS Res., Cleveland, OH and ³Med. Clin., Res. Ctr., Borstel, Germany

Background: Responses to immunization are indices of general immune competence requiring integrity of both afferent and efferent limbs of the immune system. This study was designed to examine the responses to immunization with recall and neo-antigens in persons with normal CD4+ T-cell counts after successful antiretroviral therapy.
Methods: 29 HIV-infected patients with pre-treatment CD4+ T-cell nadirs below (group A) and above (group B) 250 cells/µL and recent CD4+ T-cells > 450/µL and HIV-RNA (VL) < 400 copies/mL for > 12 months and 9 HIV-seronegative controls (group C) were immunized at study entry and 4 weeks later with tetanus toxoid (TT), diphtheria toxoid (DT), and keyhole limpet hemocyanin (KLH). Lymphocyte proliferation (LP) and delayed type hypersensitivity (DTH) responses were analysed. Lymphocyte subpopulations were analysed by 3-color flow cytometry.
Results: CD4+ T-cell nadirs averaged 40/µL in group A and 405/µL in group B. VL was <400 copies/mL for a median of 41 (group A) and 30 (group B) months. The median current CD4+ T-cell counts were 744 (group A) and 724 (group B). Absolute naļve and memory CD4+, CD4+ CD28+, CD8+, and CD8+ HLA DR38+ cell numbers were comparable among the patient groups. Following immunization, lymphoproliferation in response to TT, DT, and KLH immunization, and DTH in response to KLH immunization were comparable in the patient groups, although responses were lower in patients compared to controls (p<0.05): The median LP stimulation index (SI) in response to TT was 45, 48 and 174; inresponse to DT 2, 6, and 34; and in response to KLH 38, 38, and 223 in groups A, B, and C, respectively. Percentages of DTH responders to KLH increased from 0 to 46 in A, from 0 to 64 in B and from 0 to 100 in C.
Conclusions: Despite suppression of HIV-1 replication and restoration of CD4+ T cells to normal levels, responses to immunization remain impaired in HIV-1-infected patients. This persistent immune dysfunction has implications for the design of vaccine strategies in HIV-1 infection.