Maximum suppression of HIV replication leads to the restoration of HIV-specific responses in early HIV disease

Objectives: It is predicted that HIV-infected individuals in early HIV dise ase are the most likely group to achieve immune reconstitution following hi ghly active antiretroviral treatment. We assessed whether suppression of HI V replication in this group would improve immune function. Methods: Seventeen antiretroviral-naive patients in early HIV disease were evaluated for immune function and lymphocyte phenotyping using standard imm unological assays. Results: Absolute CD4+ T-cell number increased from a median of 550 to 800 x 10(6) cells/l while CD8+ T-cell numbers were reduced. The decrease in CD8 + cells correlated with a decrease in the CD8+ memory phenotype. Kinetics o f CD4+ naive and memory T-cell rise indicated that 80% of the maximum CD4naive increase was achieved within 18 weeks whereas maximum CD4+ memory T-c ell rise was achieved within 36 weeks. Activation markers (HLA-DR, CD38) an d an apoptosis-related marker (CD95) were reduced on CD4+ and CD8+ T cells. Lymphocyte proliferation responses to tetanus toroid, alloantigen, and ant i-CD3/CD28 were restored in patients that were initially unresponsive. At b aseline, 31% of the patients responded to HIV p24, which increased to 69% p ost-therapy. The inducible RANTES response was normalized following therapy whereas inducible interferon-gamma, interleukin (IL)-12, and MIP1 beta wer e elevated. The depressed inducible IL-10 response, however, was not altere d after therapy. Conclusions: This is one of the first studies to demonstrate the restoratio n of HIV-1 specific responses in non-acute HIV infection, suggesting early intervention with potent antiretroviral therapy may reverse immune-mediated damage not seen with treated patients who have more advanced disease. (C) 2000 Lippincott Williams & Wilkins.