CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years - The Swiss HIV cohort study

Background: Highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-1 infection allows recovery of CD4 T lymphocytes. Few studies have explored the long-term T-lymphocyte responses to HAART. Methods: Plasma HIV-1 RNA levels and CD4 and CD8 T-lymphocyte counts were longitudinally analyzed over 4 years in 2235 participants of the Swiss HIV Cohort, commencing HAART between 1996 and 1997. The CD4 T-lymphocyte count increase, the percentage of individuals with a CD4 T-lymphocyte count of 500/muL or greater and less than 200/muL, and the determinants of CD4 T-lymphocyte recovery were evaluated in individuals treated with continuous (CONT; n = 985) and discontinuous (DISCONT; n = 1250) HAART. Results: At 4 years, 69.5% of subjects (CONT, 84.5%; DISCONT, 53.6%; P < .001) showed HIV-1 RNA levels below 400 copies/mL, while the median CD4 T-lymphocyte count increased from 190/muL to 423/muL (CONT, 486/muL; DISCONT, 343/muL; P < .001). Of the 2235 participants, 38.8% (CONT, 47.7%; DISCONT, 29.4%; P < .001) reached a CD4 T-lymphocyte count of 500/muL or greater, but in 15.6%, CD4 T-lymphocyte count remained below 200/muL (CONT, 5.9%; DISCONT, 25.9%; P < .001). Larger increases in CD4 T-lymphocyte count were associated with higher baseline HIV-1 RNA, a larger percentage of undetectable HIV-1 RNA levels, lower baseline CD8 T-lymphocyte count, and younger age. Individuals reaching a CD4 T-lymphocyte count of 500/muL or greater at 4 years were characterized by higher nadir and baseline CD4 T-lymphocyte counts and a more sustained reduction of HIV-1 RNA levels. Conclusions: At 4 years, only 39% of individuals treated with HAART reached a CD4 T-lymphocyte count of 500/muL or greater, and 16% with CD4 T-lymphocyte counts less than 200/muL remained susceptible to opportunistic infections. Treatment interruptions, a poor virologic response, and older age were the major factors negatively affecting the recovery of CD4 T lymphocytes.