The Effect of Timing of Antiretroviral Therapy on CD4+ T Cell Reconstitution in the Intestine of HIV-Infected Patients

Whether and to what extent gut mucosal CD4⁺ T cells of human immunodeficiency virus (HIV)-infected patients can be restored by combination antiretroviral therapy (cART) is not well understood. We studied absolute numbers, differentiation, and activation of mucosal CD4⁺ T cells at different stages of infection and assessed the effect of timing of cART initiation on their reconstitution. Mucosal CD4⁺ T cell numbers were severely reduced at all stages of chronic infection, but normal in patients with acute infection. In patients with initiation of cART during chronic infection, mucosal CD4⁺ T cells restored to less than half of the numbers in controls. However, in patients who initiated cART during acute infection, mucosal CD4⁺ T cell numbers were fully preserved. Mucosal effector memory CD4⁺ T cell proportion normalized only if cART was initiated at >350 CD4⁺ T cells/µl but not with delayed treatment. In all treated patient groups, the activation pattern of mucosal CD4⁺ T cells did not return to normal. In conclusion, mucosal CD4⁺ T cell numbers can be preserved if cART is initiated in acute HIV infection. In chronically HIV-infected patients, early cART improves mucosal CD4⁺ T cell differentiation but cannot prevent the persistent lack of total CD4⁺ T cells.