Modeling the effects of tetanus vaccination on chronically infected HIV patients

Objective: To model the effects of vaccination with a common recall antigen on chronically infected HIV-1 patients. Background: T-cell activation plays a critical role in the initiation and propagation of HIV-1 infection and yet transient activation of the immune system is a normal response to immunization. While it is now considered wise to vaccinate HIV-1 positive patients, it is crucial to anticipate any lasting effects of vaccination on plasma HIV-1 RNA levels and on infected T cell populations. Method: We extend a simple dynamical model of HIV infection to include T cell activation by vaccination. We show that the model can reproduce many but not all of the features of the post-tetanus immunization rise in viral load observed and reported on by Stanley et al. [N. Engl. Results and conclusions: Amplitudes and approximate timing of post immunization peak viral loads were matched in nine of eleven cases; in patients with double post immunization peaks of nearly equal amplitude the later peaks were matched. Furthermore , our simulations suggest that productively infected cell populations track post-vaccination increases in plasma viral load, rising and falling in concert on a period of about 4 weeks, while chronically infected cells peak later and remain elevated over baseline levels for up to six weeks post-vaccination. Introduction T-cell activation plays a critical role in HIV infection and progression to AIDS [1–4]. In vitro studies have demonstrated the importance of cell activation in establishing productive HIV infection. For example, reverse transcription within resting cells may be incomplete and integration of proviral DNA may not occur, resulting in abortive infection [5–6]. In contrast, activated peripheral blood mononuclear cells are readily infected in culture [5–7]. The course of HIV infection in vivo appears to be influenced by cell activation. High levels of activated peripheral T cells are a predictor of early progression to AIDS [8–9], and chronic immune activation due to frequent and repeated parasitic infection has been suggested as the probable cause of the increased rate of HIV progression to AIDS and the greater susceptibility to infection observed in sub-Saharan Africa as compared to the developed countries [10–12]. Transient activation of the immune system occurs during infections and is a normal response to immunization. Such activation can affect the course of HIV infection. Numerous studies have examined the consequences of vaccinating untreated HIV-infected individuals [2, 13–17]. Stanley et al. [2] found that giving a booster dose of tetanus …