Rapid Turnover of Plasma Virions and CD4 Lymphocytes in HIV-1 Infection

In observational studies of HIV-1 pathogenesis to date, increased viral load has been shown to correlate with CD4 lymphocyte depletion and disease progression.$^{1-9}$ However, relatively little information is available on the kinetics of virus and CD4 lymphocyte turnover in vivo. In this interventional study, we administered an inhibitor of HIV-1 protease, ABT-538 (ref. 10,11), to 20 infected patients to perturb the balance between virus production and clearance. Serial measurements of subsequent changes in plasma viremia and CD4 lymphocyte counts were made, from which we have inferred kinetic information about the pretreatment steady state. Following ABT-538 administration, plasma viremia decreased exponentially in every case, with a mean half life ($T_{1/2}$) of $2.1 ± 0.4$ days. Minimum estimates of the steady-state HIV-1 production/clearance among the patients ranged from O.5 to $2.07\times 10^9$ virions/day, with a mean value of $0.68 ± 0.13\times 10^9$ virions/day. Reciprocally, CD4 lymphocyte counts increased substantially after ABT-538 use, and minimum estimates of total CD4 lymphocyte production/destruction ranged from 0.1 $7.8\times 10^9$ cells/day, with a mean value of $1.8-2.6\times 10^9$ cells/day. These findings show that HIV-1 replication in vivo is continuous and highly productive, and is associated with a rapid turnover of CD4 lymphocytes.