HIV Infection-Associated Leaky Gut: A Potential Risk Factor for Pernicious Anaemia in HIV Patients

Abstract

Background: The Human immunodeficiency virus has circulated in the human population for over 25 years. According to the World Health Organization, as of the end of the year 2022, approximately 39 million people were living with HIV infection. This increase in the number of PLWH is attributed to the use of antiretrovirals. ARTs moved HIV infection from a deadly condition into a chronic and manageable one, accompanied by non-AIDS comorbidities. Associated autoimmune complications like pernicious anaemia have been reported in PLWH. Leaky gut, a complication of HIV infection leads to the translocation of gastric content into circulation priming the immune system to respond. The translocation of self-products like intrinsic factor leads to the production of autoantibodies that destroy them. Method: The study was a case-control study with 55 each of HIV seropositive and seronegative. Haematological profiling focusing on red blood cell count, haemoglobin concentration and mean cell volume was used to detect suspected pernicious anaemia (PA) cases. LPS was measured using ELISA to detect leaky gut and translocation. Levels of intrinsic factor autoantibodies was measured in the serum using ELISA. Results: There was a higher prevalence of pernicious anaemia in the HIV cohort as compared to the HIV seronegative, > 40% against 1.8% respectively. The study showed a pronounced case of leaky gut and translocation in the PLWH as compared with the seronegative group with concentration of LPS in their serum being significantly higher (p < 0.0001). PLWH who had pernicious anaemia also had a higher concentration of serum LPS than those who had HIV but did not have pernicious anaemia (p < 0.001). Levels of LPS had a direct relation with concentration of autoantibodies with PLWH and having pernicious anaemia having higher serum concentrations than those without PA which was also higher than HIV seronegatives (p< 0.0001). Conclusion: Increased serum concentration of LPS which signifies leaky gut was observed in PLWH and suffering from pernicious anaemia. The translocation of intrinsic factor into circulation during the leaky gut led to the production of autoantibodies against intrinsic factor. This resulted in the destruction and hence unavailability of intrinsic factor for the absorption of vitamin B12.