Brief Report: Macrophage Activation in HIV-Infected Adolescent Males Contributes to Differential Bone Loss by Sex: Adolescent Trials Network Study 021.

Accumulating evidence suggests that rates of low bone mass are greater in HIV-infected males than females. Of 11 biomarkers assessed by sex and HIV-status, HIV-infected males had increased levels of soluble CD14 which inversely correlated with bone mineral content and bone mineral density measures, suggesting macrophage activation as a possible mechanism of differential bone loss

Microbial translocation and metabolic and body composition measures in treated and untreated HIV infection

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

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

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

Median % flow mediated dilation by tertile of plasma lipopolysaccharide levels among ART treated subjects in the IU study.

<p>Median % flow mediated dilation by tertile of plasma lipopolysaccharide levels among ART treated subjects in the IU study.</p

Pearson Correlation Coefficients of Markers of Microbial Translocation with Brachial Artery Flow- Mediated Dilation.

*<p>Includes all subject data from baseline A5152s evaluations and all subjects in the Indiana cross-sectional study.</p><p>ART – antiretroviral therapy. sCD14 – soluble CD14. LPS – lipopolysaccharide. Significant correlations are shown in bold.</p

Subject Characteristics.

<p>Values are means (±standard deviation) except where noted. ART – antiretroviral therapy. sCD14 – soluble CD14. LPS – lipopolysaccharide. FMD - Flow mediated dilation.</p>*<p>p = 0.02 for the difference between baseline and week 24 in ACTG 5152s subjects.</p

Association Between Breast Milk Bacterial Communities and Establishment and Development of the Infant Gut Microbiome

ImportanceEstablishment of the infant microbiome has lifelong implications on health and immunity. Gut microbiota of breastfed compared with nonbreastfed individuals differ during infancy as well as into adulthood. Breast milk contains a diverse population of bacteria, but little is known about the vertical transfer of bacteria from mother to infant by breastfeeding.ObjectiveTo determine the association between the maternal breast milk and areolar skin and infant gut bacterial communities.Design, setting, and participantsIn a prospective, longitudinal study, bacterial composition was identified with sequencing of the 16S ribosomal RNA gene in breast milk, areolar skin, and infant stool samples of 107 healthy mother-infant pairs. The study was conducted in Los Angeles, California, and St Petersburg, Florida, between January 1, 2010, and February 28, 2015.ExposuresAmount and duration of daily breastfeeding and timing of solid food introduction.Main outcomes and measuresBacterial composition in maternal breast milk, areolar skin, and infant stool by sequencing of the 16S ribosomal RNA gene.ResultsIn the 107 healthy mother and infant pairs (median age at the time of specimen collection, 40 days; range, 1-331 days), 52 (43.0%) of the infants were male. Bacterial communities were distinct in milk, areolar skin, and stool, differing in both composition and diversity. The infant gut microbial communities were more closely related to an infant's mother's milk and skin compared with a random mother (mean difference in Bray-Curtis distances, 0.012 and 0.014, respectively; P &lt; .001 for both). Source tracking analysis was used to estimate the contribution of the breast milk and areolar skin microbiomes to the infant gut microbiome. During the first 30 days of life, infants who breastfed to obtain 75% or more of their daily milk intake received a mean (SD) of 27.7% (15.2%) of the bacteria from breast milk and 10.3% (6.0%) from areolar skin. Bacterial diversity (Faith phylogenetic diversity, P = .003) and composition changes were associated with the proportion of daily breast milk intake in a dose-dependent manner, even after the introduction of solid foods.Conclusions and relevanceThe results of this study indicate that bacteria in mother's breast milk seed the infant gut, underscoring the importance of breastfeeding in the development of the infant gut microbiome

Maternal HIV infection influences the microbiome of HIV-uninfected infants.

More than 1 million HIV-exposed, uninfected infants are born annually to HIV-positive mothers worldwide. This growing population of infants experiences twice the mortality of HIV-unexposed infants. We found that although there were very few differences seen in the microbiomes of mothers with and without HIV infection, maternal HIV infection was associated with changes in the microbiome of HIV-exposed, uninfected infants. Furthermore, we observed that human breast milk oligosaccharides were associated with bacterial species in the infant microbiome. The disruption of the infant's microbiome associated with maternal HIV infection may contribute to the increased morbidity and mortality of HIV-exposed, uninfected infants