Influence of raltegravir intensification on viral load and 2-LTR dynamics in HIV patients on suppressive antiretroviral therapy

Abstract

Antiretroviral therapy can suppress HIV-1 plasma viral load to below the detection limit but cannot eradicate the virus. Whether residual ongoing viral replication persists during suppressive therapy remains unclear. A few clinical studies showed that treatment intensification with an additional drug led to a lower viral load or an increase in 2-LTR (long terminal repeat), a marker for ongoing viral replication. However, some other studies found no change in the viral load and 2-LTR. In this paper, we developed multi-stage models to evaluate the influence of treatment intensification with the integrase inhibitor raltegravir on viral load and 2-LTR dynamics in HIV patients under suppressive therapy. We analyzed one model and obtained the local and global stability of the steady states. The model and its variation predict that raltegravir intensification induces a very minor decrease in the viral load and a minor increase in 2-LTR. We also compared modeling prediction with the 2-LTR data in a raltegravir intensification study. To achieve the 2-LTR increase observed in some patients, the level of viral replication needs to be substantially high, which is inconsistent with the sustained viral suppression in patients during treatment intensification. These modeling results, together with the theoretical estimate of the upper bound of the 2-LTR increase, suggest that treatment intensification with raltegravir has a minor effect on the plasma viremia and 2-LTR in patients under suppressive therapy. Other treatment strategies have to be developed for the cure or functional control of the infection.