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Central Memory CD4⁺ T Cell Responses in Chronic HIV Infection Are Not Restored by Antiretroviral Therapy¹

Mohamed Elrefaei^2,*, Michael D. McElroy^*, Christopher P. Preas^*, Rebecca Hoh, Steven Deeks, Jeffrey Martin and Huyen Cao^*

^* California Department of Health Services, Richmond, CA 94804; and Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco, CA 94110

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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