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/microL or greater and less than 200/microL, 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/microL to 423/microL (CONT, 486/microL; DISCONT, 343/microL; P<.001). Of the 2235 participants, 38.8% (CONT, 47.7%; DISCONT, 29.4%; P<.001) reached a CD4 T-lymphocyte count of 500/microL or greater, but in 15.6%, CD4 T-lymphocyte count remained below 200/microL (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/microL 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/microL or greater, and 16% with CD4 T-lymphocyte counts less than 200/microL 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.
Kaufmann
Gilbert R
GR
Basel Center for HIV Research, Division of Infectious Diseases, University Hospital, Basel, Switzerland.
Perrin
Luc
L
Pantaleo
Guiseppe
G
Opravil
Milos
M
Furrer
Hansjakob
H
Telenti
Amalio
A
Hirschel
Bernard
B
Ledergerber
Bruno
B
Vernazza
Pietro
P
Bernasconi
Enos
E
Rickenbach
Martin
M
Egger
Matthias
M
Battegay
Manuel
M
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis*; D019562:Viral Load
D012367:RNA, Viral