HIV-infected immunological nonresponders: a characterization of gut immunity and the effects of a probiotic supplement

Worldwide today, 38 million people live with HIV and in 2020 700.000 died of HIV related disease. HIV infects CD4 T cells and causes a gradual decline in these cells. Antiretroviral treatment (ART) will in most people reconstitute the CD4 T cells, and people living with HIV on ART have life expectancy comparable to uninfected people. HIV-infected immunological nonresponders (INR) are people living with HIV who do not reconstitute their CD4 T cells on effective ART, and this group have increased risk of non-AIDS morbidity. The aims of this thesis were to describe the role of the gastrointestinal mucosal barrier and microbiome in the insufficient gain of CD4 in INR and to assess if probiotic supplement could enhance gut immunity in INR. INR had a lower number of CD4 T cells in colon, altered composition of mucosal CD4 T cells, more exhausted CD4 T cells in both the blood and gut as well as elevated markers of damage to the gastrointestinal barrier. There were no differences in the microbiome between INR and people with a sufficient response to ART. Probiotics induced changes to the microbiome in ileum, but did not affect systemic CD4 T cell count. The use of probiotics was safe in INR. Taken together; this work supports the importance of the gastrointestinal barrier and gut immunity in INR, which could be targeted with adjuvant treatment to ART