Impact of Early Antiretroviral Therapy Initiation on HIV-Specific CD4 and CD8 T Cell Function in Perinatally Infected Children

To evaluate whether the time of treatment initiation of anti-retroviral therapy in vertically HIV-infected children can impact host immune responses associated with HIV infection, as it has been suggested that early treatment can be associated with loss of HIV-specific immunity.

The study was cross-sectional in design and included a cohort of 20 perinatally-infected children with HIV that were identified at Bambino Gesu Children’s Hospital. Fourteen of the participants received early treatment which was initiated at ≤6 months of age, and 6 of the participants received late treatment which was initiated at >1 years of age. All participants had maintained virus suppression for a period of 1–10 years on anti-retroviral therapy.

Peripheral blood mononuclear cells (PBMC) were collected from participants and underwent stimulation and flow cytometry staining to ascertain quality and quantity of the HIV-specific CD4 and CD8 T-responses to HIV antigens. T cell subset maturation and functional responses were noted, and their quality was evaluated by production of cytokines after stimulation by an HIV-specific antigen.

The major maturation subsets of CD4 T cells were similar between both early and late treatment participants. However, participants who received early anti-viral treatment demonstrated superior preservation of the function and quality of HIV specific CD4 T-cells and CD8 T cells when compared with late treatment participants. While a significantly lower frequency of CD8 T cells were noted in early treatment participants, a better quality of CD8 T cells were also observed.

While previous studies have shown that early treatment is associated with greater reduction in HIV reservoir size, prevention of disease progression and longer time to viral rebound, this study also demonstrates that early initiation of anti-viral treatment may affect later outcomes and performance of CD4 and CD8 T cells.

This study demonstrates some of the potential longer-term effects of antiretroviral therapy in vertically HIV-infected children and highlights the importance of early initiation of antiviral therapy.