Central Memory CD4+ T Cell Responses in Chronic HIV Infection Are Not Restored by Antiretroviral Therapy

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Abstract
A strong CD4+ T cell response has been correlated with better control of HIV infection. However, the effect of HIV on the maintenance of Ag-specific memory CD4+ T cells is not fully understood. We characterized the function and phenotype of memory CD4+ T cells generated by mumps and influenza A or B viruses in HIV-infected individuals receiving highly active antiretroviral therapy (n = 21), HIV-infected long-term nonprogressors (n = 10), and HIV-seronegative volunteers (n = 10). We observed significantly decreased proliferation of the Ag-specific central memory CD4+ T cell population (CD28+/CCR7+/CD45RA−) in the antiretroviral treated HIV-infected individuals compared with the seronegative controls. Restored CD4+ T cell count and decreased HIV viral load while on highly active antiretroviral therapy did not result in increased proliferation, whereas nadir CD4+ T cell count predicted the presence of Ag-specific proliferation. Our results indicate that HIV infection leads to impaired maintenance of virus-induced or vaccine-generated central memory CD4+ T cells that is not restored by HAART.

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