T-cell division in human immunodeficiency virus (HIV)-1 infection is mainly due to immune activation: a longitudinal analysis in patients before and during highly active antiretroviral therapy (HAART)

In human immunodeficiency virus (HIV)-1 infection, highly increased T-cell turnover was proposed to cause exhaustion of lymphocyte production and cons equently development of AIDS. Here, we investigated cell proliferation, as measured by expression of the KI-67 nuclear antigen, in peripheral blood CD 4(+) and CD8(+) lymphocyte subpopulations before and during highly active a ntiretroviral therapy (HAART), In untreated HIV-1 infection, both the perce ntage and number of KI-67(+) CD4(+) and CD8(+) lymphocytes were significant ly increased, compared with values obtained from healthy individuals. A mor e than 10-fold increase in the percentage of dividing naive CD4(+) T cells in the blood was found when the number of these cells were below 100 per mu L.. HAART induced an immediate decline in KI-67 antigen expression, despit e often very low CD4(+) T-cell numbers, arguing against increased prolifera tion being a homeostatic response. After approximately 24 weeks of HAART tr eatment, a transient increase in the number of proliferating cells was seen , but only in the CD4(+) CD27(+) memory pool. In the CD8(+) T-cell compartm ent, the number of dividing cells was elevated 20- to 25-fold. This increas e was most notable in the CD27(+) CD 45RO(+) and CD27(-) CD45RO(+) memory C D8(+) T-cell pool, corresponding with the degree of expansion of these subs ets. Reduction of plasma HIV-RNA load by HAART was accompanied by a decreas e in numbers and percentages of dividing cells in all CD8(+) T-cell subsets . Taken together, our results indicate that peripheral T-cell proliferation is a consequence of generalized immune activation, (C) 2000 by The America n Society of Hematology.