Impact of circulating bacterial DNA in long-term glucose homeostasis in non-diabetic patients with HIV infection: cohort study.

In HIV-infected patients, the damage in the gut mucosal immune system is not completely restored after antiretroviral therapy (ART). It results in microbial translocation, which could influence the immune and inflammatory response. We aimed at investigating the long-term impact of bacterial-DNA translocation (bactDNA) on glucose homeostasis in an HIV population. This was a cohort study in HIV-infected patients whereby inclusion criteria were: patients with age >18 years, ART-naïve or on effective ART (<50 HIV-1 RNA copies/mL) and without diabetes or chronic hepatitis C. Primary outcome was the change in HbA1c (%). Explanatory variables at baseline were: bactDNA (qualitatively detected in blood samples by PCR [broad-range PCR] and gene 16SrRNA - prokaryote), ART exposure, HOMA-R and a dynamic test HOMA-CIGMA [continuous infusion of glucose with model assessment], hepatic steatosis (hepatic triglyceride content - 1H-MRS), visceral fat / subcutaneous ratio and inflammatory markers. Fifty-four men (age 43.2 ± 8.3 years, BMI 24.9 ± 3 kg/m2, mean duration of HIV infection of 8.1 ± 5.3 years) were included. Baseline HbA1c was 4.4 ± 0.4% and baseline presence of BactDNA in six patients. After 8.5 ± 0.5 years of follow-up, change in HbA1c was 1.5 ± 0.47% in patients with BactDNA vs 0.87 ± 0.3% in the rest of the sample p < 0.001. The change in Hba1c was also influenced by protease inhibitors exposure, but not by baseline indices of insulin resistance, body composition, hepatic steatosis, inflammatory markers or anthropometric changes. In non-diabetic patients with HIV infection, baseline bacterial translocation and PI exposure time were the only factors associated with long-term impaired glucose homeostasis.