Relationship between microbial translocation and endothelial function in HIV infected patients.

TitleRelationship between microbial translocation and endothelial function in HIV infected patients.
Publication TypeJournal Article
Year of Publication2012
AuthorsBlodget E, Shen C, Aldrovandi G, Rollie A, Gupta SK, Stein JH, Dubé MP
JournalPLoS One
Date Published2012
KeywordsAdult, Anti-Retroviral Agents, Biological Transport, Brachial Artery, Cardiovascular Diseases, Cohort Studies, Cross-Sectional Studies, Endothelium, Female, HIV Infections, Humans, Indiana, Lipopolysaccharide Receptors, Lipopolysaccharides, Male, Multivariate Analysis, Prospective Studies, Ultrasonography

BACKGROUND: Circulating levels of microbial products are increased in HIV infection, and provoke endothelial dysfunction in other disease settings.

METHODOLOGY/PRINCIPAL FINDINGS: We examined data from a cross-sectional single site study at Indiana University (Indiana, N = 85) and a 24- week multicenter prospective study of antiretroviral therapy (ART) initiation (ACTG 5152s, N = 75). Brachial artery flow-mediated dilation (FMD) was measured by ultrasound. Plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels were measured from stored specimens and correlated with FMD values using Pearson correlations. The Indiana subjects were 63% male with a mean age of 39 years and a median CD4 count of 406 cells/mm(3) (388 not on ART, 464 on ART). The 5152s subjects were 92% were male with a mean age of 35 years and a median CD4 count of 251 cells/mm(3) at entry which increased to 396 cells/mm(3) on ART. When analyzing the two cohorts individually or in combination neither sCD14 nor LPS correlated significantly with FMD. In a pre-specified subgroup analysis of the Indiana subjects receiving ART (N = 46, mean ART duration 40 months) LPS was inversely correlated with FMD (r = -0.33, p = 0.02), but not sCD14 (r = -0.01, p = 0.9). Multivariate analysis confirmed LPS as an independent predictor of FMD in this subgroup (p = 0.02).

CONCLUSIONS/SIGNIFICANCE: In HIV-infected individuals on prolonged ART, higher LPS levels are associated with worse endothelial function but not in untreated subjects or at 24 weeks after ART initiation. Persistent microbial translocation may contribute to arterial dysfunction and the increased cardiovascular disease risk observed in individuals on long-term ART.

Alternate JournalPLoS ONE
PubMed ID22952600
PubMed Central IDPMC3431387
Grant ListAI091492 / AI / NIAID NIH HHS / United States
RR16176 / RR / NCRR NIH HHS / United States
RR00750 / RR / NCRR NIH HHS / United States
HL72711 / HL / NHLBI NIH HHS / United States
UL1 TR000130 / TR / NCATS NIH HHS / United States