Gut innate Immune System (InImS) Biomarker Changes Are Seen in Treated HIV Patients as Compared to Non-HIV Controls

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Abstract Introduction: We have followed the onset of the acquired immune deficiency disease (AIDS) pandemic and human immunodeficiency virus (HIV) infection from its recognition in the US since 1981 (1) describing the disease’s impact on T-lymphocytes (2), leading to pulmonary and renal diseases, cancer (3) and fibrosis (4). The development of an effective therapeutic combination anti-retroviral therapy (cART) has revolutionized HIV’s impact globally and HIV infection is now regarded as a chronic disease. A major inflammatory component for chronic HIV is the gastrointestinal tract (GIT) which is a major site for HIV replication and persistence (5). However, few tools are currently available to assess the innate immune system (InImS) in HIV patients. In this study, we present data on InImS biomarkers in patients on cART showing that inflammation predicts mortality (1). Patients and Methods: From patients enrolled in a colorectal neoplasia prediction study (6) we followed 34 adult HIV positive Veterans on cART comparing colon InImS expression of a Paneth cell product, p87; the denominator) and blood ferritin (the numerator) to derive the FERAD ratio, and p87 expression by immunohistochemistry available in some of our HIV patients, and compare expression to 2,252 without HIV. Stool and colonoscopically-obtained tissue specimens were run in a p87 ELISA and immunohistochemistry for both fixed and native antigens, using the Adnab-9 antibody. Results: There were no significant differences in demographics aside from lower BMI in HIV patients (24.93±6.30 versus 28.0±6.13 kg/m2) p< 0.0001. HIV patients also had lower serum creatinine (0.99±0.23 versus 1.28±1.89; p< 0.0001) and were heavier smokers 88.9% vs 43.7% (OR 10.29[CI1.28-82.77];p< 0.008) and more frequent alcohol drinkers 71.4% vs 25.1% (OR 6.0 [CI1.7-20.9]) than controls. Native p87 antigen was elevated in HIV patients compared to controls in the ascending, transverse and descending colon (0.794±0.890 versus 0.170±0.201 respectively; p< 0.000004; 1.062±0.730 versus 0.202±0.377 respectively; p< 0.000003; and 0.611±0.182 versus 0.174±0.251 respectively; p< 0.0009), respectively; and Helicobacter pylori (H. pylori) detection was higher in HIV patients (84.6% versus 36%;p< 0.0002). We also ran these assays in cancer patients, for comparison. Conclusions: Colonic inflammation as expressed by p87, a Paneth cell product is significantly elevated in HIV patients and likely represents continued HIV activity leading to inflammation. Increased rates of smoking and drinking alcohol further contribute to inflammation, but there may be an ability to reduce p87 expression by intervention with folates (7) and manipulation of the abnormal HIV patient microbiome (8) may be effective therapies that warrant further study.

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