HIV-1 infections cannot be completely eradicated by drug therapy, as the virus persists in reservoirs. Low-level plasma viremia has been detected in patients treated for over 7 years, but the cellular compartments that support this low-level viremia have not been identified. The decay of HIV-1 during treatment appears to occur in four phases, with the 3rd and 4th phases occurring when the virus is below the limit of detection of conventional assays. Here, we focus on the 3rd phase of decay, which has been estimated to have a half-life of 39 months. We show that follicular dendritic cells (FDC), which have been identified as an HIV reservoir, can be the main source of the low-level viremia detected during the 3rd phase of decay and contribute to viremia at even longer times. Our calculations show that the kinetics of leakage of virus from FDC is consistent with three types of available clinical data.
Highly active antiretroviral therapy (HAART) is effective in suppressing progression of HIV infection. In the first few months of suppressive therapy, the plasma HIV-1 RNA load experiences a biphasic decay (1-5). The first phase has a short halflife (1 to 2 days) and is attributed to the loss of infected activated CD4 ϩ T cells. The second phase has a half-life of 1 to 4 weeks and has been attributed to the loss of long-lived infected cells such as resting CD4 ϩ T cells or macrophages (4, 6). The presence of other decay phases has been suggested (5, 7), and a recent study by Palmer et al. (8), using a very sensitive assay with a lower limit of quantification of 0.63 HIV RNA copies/ml (9), identified a third and fourth decay phase in patients on suppressive therapy for 7 years (Fig. 1). Phase 3 had a half-life, 3 , of 39 weeks (supported by a recent study [10]), and phase 4 showed a nearly constant plasma viral load for the period studied out to 7 years. Overall, the median plasma viral load, V(t), for patients on suppressive therapy can be represented by the following equation:where t is the time on therapy, V 1 (t) through V 4 (t) designate the contributions to the plasma viral load of the virus generated by the compartments 1 through 4, V 1 (0) through V 4 (0) designate the contributions of the virus generated by compartments 1 through 4 to the baseline viral load, i ϭ