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Sequencing of Bacterial Microflora in Peripheral Blood: our Experience with HIV-infected Patients
Published on: June 11, 2011
Microbial translocation and metabolic and body composition measures in treated and untreated HIV infection
Tamara Timmons1, Changyu Shen, Grace Aldrovandi
11 Department of Medicine, University of Southern California Keck School of Medicine , Los Angeles, California.
Abstract:
Circulating levels of microbial products such as lipopolysaccharide (LPS) are increased in HIV infection. Microbial translocation promotes obesity, insulin resistance, and dyslipidemia in other settings. We examined data from 178 subjects: an Indiana University (IU) cross-sectional study [N=49 on antiretroviral therapy (ART), N=47 not on ART], and a 24 week prospective study of ART initiation ACTG 5152s (N=82). Pearson correlations were used to describe relationships of plasma LPS levels and soluble CD14 (sCD14), a marker of monocyte activation, with metabolic and body composition measures. HOMA-IR (a measure of insulin resistance) and LPS were correlated for the combined cohorts (r=0.19, p=0.02), particularly in the 5152s ART-naive cohort (r=0.41, p<0.01). Triglycerides were correlated with LPS in the combined cohort (r=0.32, p<0.01), and all subsets excluding the IU on ART subset. There were negative correlations between sCD14 and high-density lipoprotein (HDL) cholesterol in all subjects (r=-0.21, p<0.01), as well as the IU subset not on ART (r=-0.32, p=0.04). Large particle HDL as measured by NMR spectroscopy, but not HDL cholesterol, was negatively correlated with LPS (r=-0.18, p=0.02), particularly among the IU subset receiving ART (r=-0.33, p=0.03). In the combined cohorts, sCD14 was negatively correlated with lean mass as well as trunk and limb fat. There is a relationship between microbial translocation markers and metabolic effects, particularly lipoproteins. During prolonged ART, microbial translocation was associated with an adverse effect on large HDL and thus may contribute to the increased cardiovascular disease risk observed during chronic treatment of HIV.
Insights
HIV infection is linked to increased microbial translocation markers, which correlate with insulin resistance and dyslipidemia. Long-term antiretroviral therapy (ART) may worsen these effects, particularly impacting HDL cholesterol and cardiovascular risk.
Area of Science:
- Infectious Diseases
- Metabolic Syndrome
- Cardiovascular Health
Background:
- Circulating microbial products like lipopolysaccharide (LPS) are elevated in HIV infection.
- Microbial translocation is associated with metabolic dysfunction, including insulin resistance and dyslipidemia.
- Antiretroviral therapy (ART) is crucial for HIV management but may have metabolic implications.
Purpose of the Study:
- To investigate the relationship between microbial translocation markers (LPS and soluble CD14) and metabolic/body composition measures in individuals with HIV.
- To assess how these relationships differ between individuals on and not on ART, and during ART initiation.
- To explore the potential contribution of microbial translocation to cardiovascular disease risk in treated HIV patients.
Main Methods:
- Analysis of data from 178 subjects across a cross-sectional study and a prospective ART initiation study.
- Utilized Pearson correlations to examine associations between plasma LPS, soluble CD14 (sCD14), and metabolic parameters (HOMA-IR, triglycerides, HDL cholesterol, body composition).
- Included measurements of large particle HDL by NMR spectroscopy.
Main Results:
- Plasma LPS correlated positively with insulin resistance (HOMA-IR) and triglycerides across combined cohorts.
- Soluble CD14 (sCD14) showed negative correlations with high-density lipoprotein (HDL) cholesterol and lean/fat mass.
- LPS was negatively associated with large particle HDL, particularly in subjects on ART, suggesting a link to adverse lipoprotein profiles.
Conclusions:
- Microbial translocation markers are associated with adverse metabolic effects, especially concerning lipoproteins, in HIV-infected individuals.
- Prolonged ART may exacerbate these effects, negatively impacting large HDL particles.
- These findings suggest microbial translocation may contribute to the elevated cardiovascular disease risk observed in chronically treated HIV patients.
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