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Defective gastrointestinal barrier function and, in turn, microbial translocation have been identified as significant contributors to persistent inflammation in antiretroviral (ARV)-treated people living with HIV. Metabolic supplementation of short-chain fatty acids (SCFAs), generally produced by the commensal microbiome, may improve these outcomes. Butyrate is a SCFA that is essential for the development and maintenance of intestinal immunity and has a known role in supporting epithelial integrity. Herein we assessed whether supplementation with the dietary supplement sodium butyrate would improve immune reconstitution and reduce inflammation in ARV-treated, simian immunodeficiency virus (SIV)-infected rhesus macaques. We demonstrate that butyrate supplementation does not significantly improve immune reconstitution, with no differences observed in systemic CD4+ T-cell frequencies, T-cell functionality or immune activation, microbial translocation, or transcriptional regulation. Our findings demonstrate that oral administration of sodium butyrate is insufficient to reduce persistent inflammation and microbial translocation in ARV-treated, SIV-infected macaques, suggesting that this therapeutic may not reduce co-morbidities and co-mortalities in treated people living with HIV. [ABSTRACT FROM AUTHOR]

Among the numerous immunological abnormalities observed in chronically HIV-infected individuals, perturbations in memory CD4 T cells are thought to specifically contribute to disease pathogenesis. Among these, functional imbalance in the frequencies of T-regulatory (Tregs) and Interleukin-17/22 (IL-17/IL-22) producing T-helper cells (Th17/Th22) from mucosal sites, and T-follicular helper cells (Tfh) in lymph nodes, are thought to facilitate specific aspects of disease pathogenesis. However, while preferential infection of Tfh cells is widely believed to create an important viral reservoir in an immunologically privileged site in vivo, whether immunological perturbations among memory CD4 T cell populations are attributable to their relative infectivity by the virus in vivo is unclear. Here we studied peripheral blood and lymphoid tissues from antiretroviral (ARV)-treated and ARV-naïve Asian macaques, and isolated functionally-defined populations of memory CD4 T cells. We then assessed the degree to which these populations were infected by SIV in vivo to determine whether or not particular functionally-identified populations of memory CD4 T cells were preferentially infected by the virus. We found that SIV did not preferentially infect Th17 cells compared to T-helper 1 (Th1) cells, T-helper 2 (Th2) cells, or Tregs. Moreover, Th17 cells contributed proportionately to the total pool of infected cells. Taken together, our data suggest that while Tfh cells are more prone to harbor viral DNA, other functionally-polarized cells are equally infected by the virus in vivo, and that Th17 cells are not preferentially infected. [ABSTRACT FROM AUTHOR]

An abstract of the article "Dynamics of Simian Immunodeficiency Virus SIVmac239 Infection in Pigtail Macaques," by Nichole R. Klatt and colleagues is presented.