Cristian Apetrei, MD, PhD, has been awarded funding in the amount of $3,898,169 for a five-year award by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK) entitled “Impact of metabolic programming of T cells from the GI tract and related tissues on HIV reservoir seeding, maintenance and reactivation.” This proposal was submitted in response to the funding opportunity entitled “Toward Elucidating Mechanisms Contributing to HIV Reservoirs in NIDDK-relevant Tissues (Cure TEAMS)” under funding opportunity number RFA-DK-20-023.
Two cases of virus eradication (the “Berlin patient” and the “London patient”) demonstrated that a cure for HIV infection is feasible. Meanwhile, the burden of the HIV epidemic, which spreads unabated, as such that for every person living with HIV (PLWH) that starts antiretroviral therapy (ART), two new people become infected, fuels the global consensus that a cure for HIV is needed to curb the epidemic. Limitations towards eradication are: (i) HIV persistence in latently infected cells invisible to immune responses, (ii) inability of a damaged/exhausted immune system to eliminate HIV-infected cells, and (iii) a state of chronic inflammation (INFL) that persists despite ART. A better understanding of HIV reservoir seeding, maintenance and reactivation will identify new strategies for effective virus eradication
This study will examine the hypothesis that administration of a Western diet (WD, i.e., rich in fat and sugars) to rhesus macaques will fuel SIV reservoir formation, maintenance, and reactivation, through changes in T cells from the gut and related lymphoid and adipose tissues. Dr. Apetrei’s team will assess the overall impact of the WD on host microbiome, metabolism, immune cell metabolic programing, immune responses, IA/INFL, and will correlate these parameters with reservoir seeding, maintenance and reactivation. This research will determine whether gut T cells are responding to either a change in dietary sugars and lipids, plasma sugar and lipid increases triggered by the WD, or to known changes in gut microbiome driven by WD. The WD-related changes will be reverted with statins. These studies may identify new strategies to curb the HIV reservoir, reverse the metabolic dysfunctions and control residual INFL. Insights gained from this work could have a major impact in the management of HIV patients, either alone or in combination with latency reversing agents, and will represent a significant step towards a better control of HIV.