Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy

The mechanism of CD4(+) T cell depletion in human immunodeficiency virus (H IV)-1 infection remains controversial. Using deuterated glucose to label th e DNA of proliferating cells in vivo, we studied T cell dynamics in four no rmal subjects and seven HIV-1-infected patients naive to antiretroviral dru gs. The results were analyzed using a newly developed mathematical model to determine fractional rates of lymphocyte proliferation and death. In CD4() T cells, mean proliferation and death rates were elevated by 6.3- and 2.9 -fold, respectively, in infected patients compared with normal controls. In CD8(+) T cells, the mean proliferation rate was 7.7-fold higher in HIV-1 i nfection, but the mean death rate was not significantly increased. Five of the infected patients underwent subsequent deuterated glucose labeling stud ies after initiating antiretroviral therapy. The lymphocyte proliferation a nd death rates in both CD4(+) and CD8(+) cell populations were substantiall y reduced by 5-11 weeks and nearly normal by one year. Taken together, thes e new findings strongly indicate that CD4(+) lymphocyte depletion seen in A IDS is primarily a consequence of increased cellular destruction, not decre ased cellular production.