HIV and antiretroviral therapy-induced alterations in metabolism, adipose tissue, and gut microbiota in people with HIV
Year: 2025
Type: dissertation
Abstract: In recent years, concerns have been raised about the increasing prevalence of obesity among people with HIV (PWH). Alongside obesity, metabolic co-morbidities such as diabetes mellitus (DM) and non-alcoholic fatty liver disease (NAFLD) have become common in PWH. While often linked to lifestyle factors, some antiretrovirals have also been associated with weight gain. However, the biological mechanisms behind HIV and/or ART-related metabolic changes remain unclear. Study I assessed the prevalence of obesity, insulin resistance, and DM in Finnish-born PWH (n=1041), and compared them to the prevalence rates of individuals from the FinHealth 2017 study (n=7047) representing the general population. In this study, obesity was less common among PWH, but the adjusted prevalence of DM was similar to that of the general population. Insulin resistance was more common at any given BMI among PWH, while HbA1c levels were lower. Studies II–IV were sub-studies of a randomized trial evaluating the metabolic effects of switching from EFV or a protease inhibitor (PI) to raltegravir (RAL-group) versus continuing unchanged antiretroviral therapy (EFV/PI group) in PWH (n=43) at risk for NAFLD. Studied outcomes included liver fat, body composition, metabolic markers, gut microbiota, and subcutaneous adipose tissue (SAT) transcriptome. Assessments were done at baseline and week 24. Comparisons were also made with people without HIV (PWoH, n=10). In Study II, liver fat was surprisingly normal at baseline and it remained unchanged after the antiretroviral switch. However, body weight and SAT volume increased in the RAL group but stayed stable in the EFV/PI group. Adipocyte size, total, LDL, and HDL cholesterol, and inflammatory markers decreased in the RAL group. In Study III, gut microbiota α-diversity was lower in the EFV group than in PWoH at baseline. After switching to RAL, α-diversity increased and did not differ from that of PWoH by week 24. The PI group showed no difference in gut microbiota α-diversity compared to PWoH. In Study IV, SAT transcriptome in PWH differed from PWoH in only 51 out of 19,930 genes (FDR < 0.05), suggesting a modest impact of modern ART. However, we observed downregulation of mitochondrial genes in PWH, which may contribute to metabolic dysregulation. Switching to RAL did not significantly alter SAT transcriptome. In conclusion, despite modern, effective ART, metabolic complications persist. Ongoing efforts are needed to monitor and manage these risks in PWH, given their lifelong need for HIV treatment.
Source: Työväentutkimus Vuosikirja
Author: Hanttu, Anna
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7197730490