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OBJECTIVES To characterize monocyte subsets and activation in persons living with HIV (PLWH) with tuberculosis coinfection. DESIGN Cross-sectional study within a cohort of PLWH and HIV-uninfected participants at the Joint Clinical Research Centre in Kampala, Uganda. METHODS Participants were at least 45 years old with at least one cardiovascular risk factor. PLWH had an HIV viral load 1000 copies/ml or less on stable antiretroviral therapy prior to cohort entry. QuantiFERON-TB testing was performed to define latent tuberculosis infection (LTBI). Prior active TB was defined by self-report and verified by medical records. Blood was stained with monocyte subset markers (CD14+, CD16), CD62p, CD69, CX3CR1, HLA-DR, and tissue factor, and examined with flow cytometry. RESULTS One hundred and twenty-five participants (83 PLWH and 42 without HIV) were included. Median CD4+ count was 582 cells/μl in PLWH. PLWH had a higher frequency of total monocytes (4.3% vs. 3.2%; P

BACKGROUND Selenium, zinc, and chromium are essential micronutrients. Their alterations have been associated with HIV disease progression, metabolic complications, and mortality. METHODS This is a cross-sectional study in children with perinatally acquired HIV (PHIV, n = 57), HIV-exposed uninfected (HEU, n = 59), and HIV-unexposed uninfected (HIV-, n = 56) children aged 2 to 10 years old, age- and sex-matched, enrolled in Uganda. PHIV were on stable antiretroviral therapy (ART) with undetectable viral load. We measured plasma concentrations of selenium, zinc, and chromium as well as markers of systemic inflammation, monocyte activation, and gut integrity. RESULTS Among PHIV children, 93% had viral load ≤20 copies/mL, median CD4 was 37%, and 77% were receiving a nonnucleotide reserve transcriptase regimen. Median age of all participants was 8 years and 55% were girls. Median selenium concentrations were higher in PHIV compared with the HEU and HIV groups (P

Women with HIV may experience higher rates of non-AIDS comorbidities compared to men with HIV, but the underlying mechanisms are not well understood. We investigated sex-related differences in the effects of HIV on monocyte phenotypes within the Ugandan Study of HIV effects on the Myocardium and Atherosclerosis (mUTIMA). Of 133 participants who provided blood for flow cytometry assays, 86 (65%) were women and 91 (68%) were persons living with HIV (PLWH) on antiretroviral therapy. The median age was 57 (interquartile range, 52–63) years. PLWH exhibited a lower proportion of circulating CD14+CD16- classical monocytes (66.3% vs. 75.1%, p &lt, 0.001), and higher proportion of CD14+CD16+ inflammatory monocytes (17% vs. 11.7%, p = 0.005) compared to HIV-uninfected participants. PLWH had an increased expression of the chemokine receptor CX3CR1 in total monocytes (CX3CR1+ monocytes, 24.5% vs. 4.7%, 0.001) and monocyte subsets. These findings were generally similar when analyzed by sex, with no significant interactions between sex and HIV status in adjusted models. Our data show that the inflammatory monocyte subset is expanded and monocyte CX3CR1 chemokine receptor expression is enhanced among PLWH, regardless of sex. Whether these parameters differentially affect risk for non-AIDS comorbidities and clinical outcomes in women with HIV requires additional investigation.

OBJECTIVES The risk of cardiometabolic complications in children with perinatally acquired HIV infection (PHIVs) and in perinatally HIV-exposed but uninfected children (HEUs) and its relationship to systemic inflammation and markers of gut integrity are not well established. In this current study, we assed insulin resitance in PHIV compared to HEUs and HIV unexposed uninfected children and explored potential association with intestinal damage biomarkers. METHODS This was a cross-sectional study in PHIVs, HEUs and HIV-unexposed, uninfected children (HUUs) aged 2-10 years enrolled in Uganda. PHIVs were on stable antiretroviral therapy (ART) with HIV viral load

Background Tuberculosis (TB) has been linked to an increased risk of atherosclerotic cardiovascular disease (ASCVD). We assessed whether latent TB infection (LTBI) is associated with subclinical coronary atherosclerosis in 2 TB-prevalent areas. Methods We analyzed cross-sectional data from studies conducted in Lima, Peru, and Kampala, Uganda. Individuals ≥40 years old were included. We excluded persons with known history of ASCVD events or active TB. Participants underwent QuantiFERON-TB (QFT) testing to define LTBI and computed tomography angiography to examine coronary atherosclerosis. A Coronary Artery Disease–Reporting Data System (CAD-RADS) score ≥3 defined obstructive CAD (plaque causing ≥50% stenosis). Results 113 and 91 persons with and without LTBI, respectively, were included. There were no significant differences between LTBI and non-LTBI participants in terms of age (median [interquartile range]; 56 [51–62] vs 55 [49–64] years; P = .829), male sex (38% vs 42%; P = .519), or 10-year ASCVD risk scores (7.1 [3.2–11.7] vs 6.1 [2.8–1.8]; P = .533). CAD prevalence (any plaque) was similar between groups (29% vs 24%; P = .421). Obstructive CAD was present in 9% of LTBI and 3% of non-LTBI individuals (P = .095). LTBI was associated with obstructive CAD after adjusting for ASCVD risk score, HIV status, and study site (adjusted OR, 4.96; 95% CI, 1.05–23.44; P = .043). Quantitative QFT TB antigen minus Nil interferon-γ responses were associated with obstructive CAD (adjusted OR, 1.2; 95% CI, 1.03–1.41; P = .022). Conclusions LTBI was independently associated with an increased likelihood of subclinical obstructive CAD. Our data indicate that LTBI is a nontraditional correlate of ASCVD risk.

Introduction: Latent tuberculosis infection (LTBI) has been associated with increased odds of acute myocardial infarction. Here we assessed the relationship between subclinical coronary atherosclerosis, LTBI status, and Mycobacterium tuberculosis ( Mtb )-specific cell-mediated responses. Hypothesis: LTBI and the magnitude of Mtb -specific cell-mediated responses are associated with increased rates of subclinical coronary artery disease (CAD). Methods: Cross-sectional study within a cohort of HIV-infected and -uninfected participants enrolled at the Joint Clinical Research Centre in Kampala, Uganda. Participants were ≥45 years with at least one risk factor for cardiovascular disease. Persons living with HIV (PLWH) were on stable antiretroviral therapy with HIV viral load ≤1,000 copies/mL within the 6 months prior to study entry. Participants underwent QuantiFERON®-TB Gold (QFT) testing to define LTBI status. Interferon-γ (IFN-γ) cell-mediated responses to Mtb antigens contained in the QFT TB tube were extracted. Participants underwent coronary computed tomography angiography (CCTA) utilizing a 128-slice Siemen’s scanner. Obstructive CAD was defined as having at least one coronary segment with plaque causing ≥ 50% luminal stenosis (CAD-RADS ≥3). Results: Of 138 participants, 66 (48%) had LTBI (17 PLWH and 49 HIV-uninfected), and 72 (52%) were non-LTBI (38 PLWH and 34 HIV-uninfected). Median age was 57 years; 91 (66%) were female; 120 (87%) had hypertension, 45 (33%) had diabetes mellitus, 24 (17%) had dyslipidemia, and 7 (5%) used tobacco. Median CD4 count was 569 cells/uL in PLWH. Prevalence of obstructive CAD was 9% in LTBI vs. 3% in non-LTBI; p =0.152. Mtb -specific responses were higher in persons with obstructive CAD compared to those without it (IFN-γ IU/mL median [IQR]; 5 [0.4 - 9.6] vs. 0.3 [0.1 - 2.9]; p =0.04). Mtb -specific responses remained associated with obstructive CAD after adjusting for age, sex, HIV status, cholesterol, hypertension, tobacco use, and diabetes mellitus (adjusted OR, 1.33; 95% CI; 1.04 - 1.7). Conclusions: Higher Mtb -specific cell-mediated responses were associated with obstructive CAD. Our findings suggest that Mtb contributes to coronary plaque burden independently of HIV and cardiovascular risk factors.

We aimed to evaluate differences in socio-economic variables in a Ugandan cohort of children with perinatally acquired HIV (PHIVs), HIV exposed uninfected (HEU) and HIV unexposed uninfected (HIV-) children and their associations with markers of inflammation and intestinal integrity. This is a cross-sectional study in 57 PHIV, 59 HEU and 56 HIV - children aged 2-10 years old enrolled in Uganda. Mean age of all participants was 7 years and 55% were girls. Compared to HEU and HIV - children, PHIVs were more likely to have parents that only completed a primary education, live in a household without electricity and live in poverty (p≤0.034). PHIVs living in poverty had higher IL-6 (p=0.006), those with lack of electricity had higher hsCRP, IL6, sTNFRII and d-dimer (p≤0.048) and PHIVs with an unprotected water source had higher IL6 and d-dimer (p≤0.016). After adjusting for demographic and HIV variables, IL-6 and d-dimer remained associated with lack of electricity and having an unprotected water source only in PHIVs (p

BackgroundChildren with perinatally acquired human immunodeficiency virus (HIV; PHIVs) face a lifelong cumulative exposure to HIV and antiretroviral therapy (ART). The relationship between gut integrity, microbial translocation, and inflammation in PHIV is poorly understood.MethodsThis is a cross-sectional study in 57 PHIVs, 59 HIV-exposed but uninfected children, and 56 HIV-unexposed and -uninfected children aged 2–10 years old in Uganda. PHIVs were on stable ART with HIV-1 RNA ResultsThe mean age of all participants was 7 years and 55% were girls. Among PHIVs, the mean CD4 % was 34%, 93% had a viral load ≤20 copies/mL, and 79% were on a nonnucleoside reverse transcriptase inhibitor regimen. Soluble cluster of differentiation 14 (sCD14), beta-D-glucan (BDG), and zonulin were higher in the PHIV group (P ≤ .01). Intestinal fatty acid binding protein (I-FABP) and lipopolysaccharide binding protein (LBP) did not differ between groups (P > .05). Among PHIVs who were breastfed, levels of sCD163 and interleukin 6 (IL6) were higher than levels in PHIV who were not breastfed (P < .05). Additionally, in PHIVs with a history of breastfeeding, sCD14, BDG, LBP, zonulin, and I-FABP correlated with several markers of systemic inflammation, including high-sensitivity C-reactive protein, IL6, d-dimer, and systemic tumor necrosis factor receptors I and II (P ≤ .05).ConclusionsDespite viral suppression, PHIVs have evidence of altered gut permeability and fungal translocation. Intestinal damage and the resultant bacterial and fungal translocations in PHIVs may play a role in the persistent inflammation that leads to many end-organ diseases in adults.Despite viral suppression, children with perinatally acquired human immunodeficiency virus (HIV) in Uganda have evidence of alterations in intestinal permeability and fungal translocation, compared to HIV-exposed but uninfected and HIV-unexposed children, which may play a role in HIV-associated chronic inflammation.