The extent of HIV-1-related immunodeficiency and age predict the long-term CD4 T lymphocyte response to potent antiretroviral therapy.

Abstract

To study the long-term immunological recovery in HIV-1-infected individuals receiving potent antiretroviral therapy (ART). Prospective, observational study. Plasma HIV-1 RNA, CD4 and CD8 T lymphocyte counts were determined at 3-6 monthly intervals in 95 HIV-1-infected subjects receiving ART who suppressed plasma HIV-1 RNA to levels below 400 copies/ml during a median observation period of 45 months. The median CD4 cell count rose from 325 to 624 cells/microl at 48 months, increasing by 22.6 cells/microl per month in the first 3 months, 8.1 cells/microl per month from months 3 to 12, 6.8 cells/microl per month in the second year, 3.3 cells/microl per month in the third, and 1.7 cells/microl per month in the fourth year. At 48 months, 98% of subjects reached CD4 cell counts > 200 cells/microl, 86% > 350 cells/microl, and 74% > 500 cells/microl. A higher nadir CD4 cell count and younger age were independently associated with greater increases in CD4 cell counts, and higher absolute CD4 cell counts at 48 months. Poor immunological responders who did not reach 500 CD4 lymphocytes/microl at 48 months showed lower nadir and baseline CD4 cell counts than good responders (99 versus 300 cells/microl and 160 versus 373 cells/microl, respectively). The recovery of CD4 T lymphocytes occurs mainly in the first 2 years after the initiation of ART, and is associated with age and the pre-existing degree of HIV-1-related immunodeficiency, suggesting that the long-term exposure to HIV-1 infection has caused damage to the immune system that is difficult to correct.