Immune function and phenotype before and after highly active antiretroviral therapy

Area of Science:

• Immunology
• Virology
• Cellular Biology

Background:

• Highly active antiretroviral therapy (HAART) has transformed HIV management, but its long-term effects on immune cell populations and function require continued investigation.
• Understanding immune reconstitution post-HAART is crucial for predicting patient outcomes and managing potential complications like opportunistic infections.

Purpose of the Study:

• To investigate immune function changes in HIV-infected patients with stable CD4+ T cell counts before and after long-term HAART.
• To assess alterations in T cell activation markers, proliferation capacity, natural killer (NK) cell subsets, and cytokine production.

Main Methods:

• Analysis of immune markers in 12 HIV-infected patients with matched CD4 counts pre- and post-HAART.
• Flow cytometry to evaluate CD28 and CD38 expression on T cells and NK cell subsets.
• Lymphocyte proliferation assays stimulated with mitogens and Candida.
• Measurement of interferon-gamma and macrophage inflammatory protein-1gamma production.

Main Results:

• Post-HAART, CD8+ T cells showed increased CD28 and decreased CD38 expression, with fewer CD4+CD28+ T cells expressing CD38.
• Lymphocyte proliferation increased significantly, correlating with CD28 expression on T cells.
• The proportion of CD56+ NK cells increased, while CD16+ NK cells decreased.
• Interferon-gamma production was elevated post-HAART.

Conclusions:

• Long-term HAART leads to immune repopulation with T cells exhibiting reduced activation markers (CD38) and enhanced proliferative capacity (CD28).
• Changes in NK cell populations and increased interferon-gamma suggest a more robust immune response.
• These findings have clinical implications for assessing vulnerability to opportunistic infections in patients on long-term HAART.