Impact of early cART in the gut during acute HIV infection

Abstract

Early after HIV infection there is substantial depletion of CD4+ T cells in the gastrointestinal (GI) tract lamina propria (LP), with associated epithelial barrier damage, leading to microbial translocation and systemic inflammation and immune activation. In this study, we analyzed these early events in the GI tract in a cohort of Thai acute HIV-infected patients and determined the effect of early combination antiretroviral treatment (cART). HIV-uninfected and chronically and acutely HIV-infected patients at different Fiebig stages (I–V) underwent colonic biopsies and then received cART. Immunohistochemistry and quantitative image analysis were performed on cross-sectional and longitudinal colon biopsy specimens (day 0 to week 96) to measure GI tract damage (infiltration of polymorphonuclear cells), inflammation (M×1, TNF-α), immune activation (Ki-67), and the CD4+ T cell population in the LP. The magnitude of GI tract damage, immune activation, and inflammation was significantly increased, with significantly depleted CD4+ T cells in the LP in all acutely infected groups prior to cART compared with HIV-uninfected control participants. While most patients treated during acute infection resolved GI tract inflammation and immune activation back to baseline levels after 24 weeks of cART, most acutely infected participants did not restore their CD4+ T cells after 96 weeks of cART.

African green monkeys avoid SIV disease progression by preventing intestinal dysfunction and maintaining mucosal barrier integrity

“…Interestingly, the AGMs actually had similar levels of neutrophils in the gut to some of the chronically infected RMs and to RMs during early acute infection [62]. Historically, it has been shown that both uninfected RMs [73] and HIV-uninfected patients [53,112] tend to have very small numbers of neutrophils resident in the gut, so their presence in AGMs suggests some role in responding to SIV infection. One possible explanation is that the resident gut neutrophils respond immediately to any possible leakage, no matter how minimal, from the gut lumen during the acute infection, through mechanisms like phagocytosis and the release of NETs [113,114].…”

Microbial Translocation and Inflammation Occur in Hyperacute Immunodeficiency Virus Infection and Compromise Host Control of Virus Replication

“…Although evidence exists[42], it is not currently clear whether microbial translocation occurs in hyperacute HIV infection, but studying early HIV infection requires longitudinally sampling people likely to become infected, which is ethically complicated given the demonstrated efficacy of pre-exposure prophylaxis.…”

Reverse geroscience: how does exposure to early diseases accelerate the age‐related decline in health?

“…73 Elimination of senescent cells via senolytics-drugs that are able to push senescent cells to apoptosis-may have profound antiaging effects. 74 After the initial HIV infection, gut lymphoid tissue is decimated and recovery after ART is incomplete, 75 leading to increased translocation of microbes and microbial products that incite inflammation. Altered gut immune response is also associated with changes in the gut microbiome that may play a role in HIV-related inflammation.…”