Background: Following HAART, the HCMV-specific T-cell-mediated immunity was investigated in AIDS patients to elucidate the level of immune reconstitution.

Methods: 2 groups of HCMV-seropositive AIDS patients with pre-HAART CD4⁺ T-cell count <50/mL and no lymphoproliferative response (LPR) were examined prospectively after 43±5 months of HAART, and 10±4 months later: group A (n=13, CD4+ at entry 357±210) with previous HCMV disease, and group B (n=13, CD4+ at entry 398±215) with no HCMV disease. A group of HAART-naive patients was also examined prospectively up to 12±5 months of HAART (n=7, CD4+ 41±33 at entry and 267±236 at the end of follow-up). The frequency of HCMV-specific CD4+ was determined by cytokine flow cytometry (CFC) after short-term activation and was considered positive when >0.1% and >400/mL blood. LPR was determined in parallel. The frequency of CD8+ T-cells specific for an immunodominant epitope of HCMV pp65 was determined by using HLA-A*02 or B*07 tetramers and was considered positive when >0.05%.

Results: The frequencies of patients with CD4+ specific T cells at the onset and at the end of follow-up were: 61.5% and 69.2% in group A; 84.6% and 53.8% in group B; and 0 and 28.5% in the naive group. Agreement of CFC and LPR was found in 78.8% of samples. Specific-CD8+ T cells were detected in 4/6 patients with CD4+ T-cell response (46±6 months of HAART, CD4+ 201±162/mL and specific CD8+ 0.87±1.15%) and in 6/7 patients with no CD4+ immune response (35±21 months of HAART, CD4+ 200±142/mL, and specific CD8+ 1.39±1.75%; the negative patient had HCMV viremia).

Conclusions: After 43 months of HAART a fair proportion of AIDS patients with pre-HAART CD4+ T cells <50/mL did not reconstitute the CD4-specific immune response, and in group B 30% of patients lost immune response after 10 months follow-up; CFC and LPR agreed in about 80% of samples in detecting HCMV T-helper response; in the great majority of patients with no CD4+ immune response, HCMV-specific CD8+ were detected in the absence of HCMV disease, thus suggesting that CD8+ might protect against HCMV disease.