In Vivo Assessment of Antiviral Reactivity in Chronic HIV Infection

Purpose And Method: Chronic infection with HIV renders individuals incapable of mounting an effective host antiviral response, as defined by in vitro assays. Therefore, to determine whether antiviral reactivity could be detected in vivo, we interrupted effective antiviral treatment prospectively in nine chronically infected aviremic individuals. Low-dose interleukin-2 (IL-2) was administered before and after treatment interruption to compensate for any potential IL-2 production deficiency. In vivo antiviral reactivity was monitored subsequent to the interruption of antiviral therapy via viral and lymphocyte dynamics. The study was terminated when the plasma HIV RNA concentration reached a plateau, defined as four successive determinations that were <25% from the mean.

Results: Plasma viral relapse occurred in all participants; reaching a peak concentration within 2.5 weeks. However, over the subsequent 2 weeks viremia was reduced an order of magnitude coincident with a 2-fold lymphocytosis of the CD8 + T cell subset. A second treatment interruption resulted in attenuation of the peak and trough virus concentrations by <10-fold in 3 of 4 participants, while the CD8 + T cell concentrations remained elevated.

Conclusion: These findings indicate that chronic HIV infection prior to successful antiviral therapy does not preclude host antiviral reactivity. In addition, in vivo antiviral reactivity as revealed by viral and lymphocyte dynamics after antiviral treatment interruption can be useful to monitor the efficacy of different therapies.