Multiple CD4(+) cell kinetic patterns and their relationships with baseline factors and virological responses in HIV type 1 patients receiving highlyactive antiretroviral therapy

This exploratory analyses characterizes patterns of lymphocyte recovery in HIV-1-infected patients treated with highly active antiretroviral therapy ( HAART) and investigates their relationship with baseline indices and virolo gic responses. We modeled kinetics of total CD4(+) lymphocytes, as well as naive (CD45RA(+)CD62L(+)), and memory (CD45RA(-)CD45RO(+)) subsets in 48 pa tients treated with AZT/3TC/Ritonavir for 48 weeks in ACTG protocol 315. Ce ll kinetic indices were estimated by nonlinear regression methods and were correlated with baseline factors and virologic responses. Five different ki netic patterns were identified, including biphasic growth, growth-plateau, growth-depletion, decay-recovery, and biphasic decay. Although overall mean lymphocyte responses showed a biphasic increase in cell number, a careful investigation reveals that only one-third of patients actually followed the biphasic growth pattern in CD4(+) cell response, while 44% of 48 patients from this study followed the growth-depletion pattern. CD4(+) cell recovery during the first phase and the 48-week study period were negatively correl ated with baseline CD4(+) cell counts, and positively correlated with basel ine viral load. Memory CD4(+) cell recovery during the first phase was also negatively correlated with baseline memory CD4(+) and total CD4(+) cell nu mber, but the recovery rate of memory CD4(+) cells during the second phase was positively correlated with baseline CD4(+) cell number. Patients with a decay in CD4(+) cell count during treatment were more likely to have exper ienced virological rebound (58%) than patients with nondecay patterns (24%) . The rate and magnitude of the absolute increase in total CD4(+) and memor y CD4(+) cell number (but not naive CD4(+) cells) during the second phase w ere lower in patients with viral rebound compared with patients with persis tent viral suppression. These results show that the kinetics of lymphocyte reconstitution in response to potent antiretroviral therapy in individual p atients vary considerably from the "classic" biphasic increase that charact erizes the mean or median response pattern. Pattern analysis of lymphocyte kinetics may be useful for testing relationships among factors that modulat e the response to treatment.