Immuno-modulatory strategies for reduction of HIV reservoir cells. (7th May 2015)

• Record Type: Journal Article
• Authors: Banks, H.T.; Flores, Kevin B.; Hu, Shuhua; Rosenberg, Eric; Buzon, Maria; Yu, Xu; Lichterfeld, Matthias
• Is Part Of: Journal of theoretical biology. Volume 372(2015)
• Page Start: 146
• Page End: 158
• Publication Date: 2015-05-07
• Subjects: Immune response -- Mathematical model -- Inverse problem -- Stability analysis; Biology -- Periodicals; Biological Science Disciplines -- Periodicals; Biology -- Periodicals; Biologie -- Périodiques; Theoretische biologie; Biology; Periodicals; 571.05
• DOI: 10.1016/j.jtbi.2015.02.006
• Languages: English
• ISSNs: 0022-5193

Abstract

Abstract: Antiretroviral therapy is able to suppress the viral load to below the detection limit, but it is not able to eradicate HIV reservoirs. Thus, there is a critical need for a novel treatment to eradicate (or reduce) the reservoir in order to eliminate the need for a lifelong adherence to antiretroviral therapy, which is expensive and potentially toxic. In this paper, we investigate the possible pharmacological strategies or combinations of strategies that may be beneficial to reduce or possibly eradicate the latent reservoir. We do this via studies with a validated mathematical model, where the parameter values are obtained with newly acquired clinical data for HIV patients. Our findings indicate that the strategy of reactivating the reservoir combined with enhancement of the killing rate of HIV-specific CD8+ T cells is able to eradicate the reservoir. In addition, our analysis shows that a targeted suppression of the immune system is also a possible strategy to eradicate the reservoir. Abstract : Highlights: We investigate possible strategies to eradicate the reservoir via a validated model. Reactivating latently infected cells is not sufficient to eradicate the reservoir. Raising the efficacy of CD8+ T cells is essential to make activation strategy work. A proper suppression of the immune system may assist in eradicating the reservoir.