Background:  CD4⁺ T-cell count alterations in HIV-infected patients are coupled with concordant modifications of CD4⁺ T-cell apoptosis. Our aim was to describe cellular characteristics associated with apoptosis in patients presenting undetectable viral load without T-cell gain.

Methods:  Undetectable viral load and any CD4⁺ T-cell gain were the inclusion criteria. T-cell apoptosis as well as T-cell subsets and monocyte phenotype were studied using cytofluorometric techniques through the following molecules on T cells:  CD28, CTLA-4, CD69, CD95, and CD80 and CD86 expression on monocytes; naïve CD4⁺ T cells were defined as CD45RA⁺CD62L⁺. Interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-a) synthesis were measured at the cellular level; 19 healthy subjects were analyzed as controls.

Results: Of 66 patients presenting with inclusion criteria, 52 were studied, among whom 21 patients (40%) exhibited normal level of CD4⁺ T-cell apoptosis, the latter being correlated to the percentage of naive CD4⁺ T cells: R² = 0.15, p< 0.001. Patients showed a higher CD4⁺CTLA-4⁺/CD4⁺ T-cell ratio compared to controls:  it was 0.12 (0 to 0.33) vs 0.07 (0 to 0.14), p = 0.051. There were similar findings for CD8⁺ T cells (p = 0.034). Also, any IL-2 synthesis was detectable while comparable level of TNF-a synthesis was found, compared to controls. Among patients, those with normal level of apoptosis were characterized by a longer mean duration of undetectable viral load than those exhibiting enhanced apoptosis:  28 vs 12 months, p = 0.007, and a higher expression (mean fluorescence intensity) of CD86 on monocytes:  65±20 vs 53±19, p = 0.046.

Conclusions:  Enhanced CD4⁺ T-cell apoptosis is not systematically observed in patients with effective ART without CD4⁺ T-cell gain, being related to the duration of undetectable viral load, thymic output, and B7.2 expression on monocytes.