Table 1.

Summary Points on Nutrition and Immune Activation

Enteropathy due to a confluence of environmental factors, nutrition deficits, and viral effects impairs mucosal barrier integrity and immune defenses and contributes to both innate and cellular immune activation in malnourished human immunodeficiency virus (HIV)–infected persons.

A gastrointestinal dysbiosis, characterized by increased Proteobacteria and reduced or altered Bacteroidetes and Firmicutes concentrations, is present in HIV-infected patients, and these changes are accompanied by increased mucosal and circulating T-cell activation and systemic inflammation. Similar phylum-level changes occur in malnutrition, but the microbiome consequences of comorbid HIV infection and malnutrition are unknown.

Malnutrition is associated with reduced T-cell proliferative responses, reduced T-cell expression of activation and memory surface markers, greater type 2 T-helper cell (TH2) polarization, and decreased TH1 cell interferon γ and interleukin 2 production, which compound HIV-related immunodeficiency and impair clearance or control of secondary infections.

Adipocytes constitutively express interleukin 6, tumor necrosis factor α, and other cytokines, and obese HIV-infected persons have substantially higher circulating levels of inflammation biomarkers. Because these cytokines derive from adipocytes as opposed to other tissues (eg, inflamed arterial vessels), obesity may confound previously reported associations between inflammation and health outcomes in HIV-infected persons.

A higher body mass index is associated with more robust CD4+ T-cell recovery during antiretroviral therapy, and obesity in is associated with higher circulating T-cell counts, increased T-cell activation, and CD4+ T-cell TH1 polarization in studies of HIV-negative individuals.

CD4+ T cells express a receptor for leptin, an adipokine produced by adipocytes, which may have an endocrine function modulating T-cell proliferation, activation, and T-helper cell polarization in states of both malnutrition and obesity.

Clinical trials of growth hormone–releasing hormone (GHRH) have shown a beneficial effect for reducing visceral and hepatic fat without the added insulin resistance observed in studies of recombinant growth hormone. However, the effect of GHRH on innate and cellular immune activation is still unclear.