Persons who inject drugs (PWID) in Kenya face a high HIV burden (18

Inflammation is a risk factor for cardiometabolic disease in people living with HIV (PLWH), yet immune mechanisms driving metabolic dysfunction remain poorly defined. We previously identified CX3CR1⁺GPR56⁺CD57⁺ (CGC⁺) CD4⁺ T cells as an expanded population associated with metabolic disease in PLWH. Here, we show that peripheral blood mononuclear cells (PBMCs) from human donors induce insulin resistance when transferred into MHC class I/II-deficient NOD scid gamma (NSG) mice maintained on a high-fat diet (HFD). PBMC-recipient HFD-fed mice exhibited increased weight gain and reduced insulin sensitivity compared with HFD-fed controls and mice on standard chow diet (SCD). In mice receiving PBMCs from PLWH, weight gain correlated with the frequency of CGC⁺ CD4⁺ T cells in donor PBMCs. Notably, adoptive-transfer of purified CGC⁺ CD4⁺ T cells was sufficient to induce insulin resistance, establishing causality. Proteomic analyses revealed enrichment of lipid-handling and mitochondrial oxidative phosphorylation in CGC⁺ CD4⁺ T cells from PLWH with diabetes. Together, these findings identify CGC⁺ CD4⁺ T cells as immune drivers of diet-dependent metabolic dysfunction.

Background: Coronary artery disease (CAD), tuberculosis (TB), and HIV are major global health concerns. Individuals affected by one or more of these conditions often exhibit chronic inflammation and immune dysregulation, with monocytes playing a central role. Monocyte subsets are known to expand in individuals with HIV, TB, or CAD, but the mechanisms by which these cells contribute to inflammation and immune responses remain poorly understood. Methods: We employed high-dimensional mass cytometry to characterize monocyte heterogeneity in 61 Ugandan adults with varying combinations of HIV, TB, and subclinical or overt CAD. An integrative approach was used, combining manual gating, unsupervised clustering, and machine learning to identify distinct monocyte phenotypes associated with CAD and TB. Monocyte activation markers soluble CD14 (sCD14) and sCD163 were measured in plasma. CAD was diagnosed by coronary computed tomography angiography. TB was determined by a questionnaire and interferon-gamma release assay (IGRA) testing. Results: Participants’ demographics and clinical characteristics were similar by CAD or HIV/TB status. Median age was 61 years; 37.7% were female. People living with HIV and latent TB or prior active TB had higher sCD14 plasma levels compared with HIV/TB-negative individuals. Individuals with CAD showed reduced surface expression of the scavenger receptor CD163 on non-classical monocytes. Unsupervised clustering further revealed 2 distinct non-classical monocyte subsets associated with disease states: A CD86dim CX3CR1dim CD45RA+ GPR56+ CXCR3+ subset significantly depleted in individuals with CAD, and a CD86+ CX3CR1++ CD45RA++ GPR56- CD38- CXCR3- subset enriched in individuals with latent TB. Conclusions: These findings underscore the complexity of the monocyte landscape in CAD progression, particularly in regions where HIV and TB are co-endemic. Our study reveals distinct alterations within 2 non-classical monocyte subpopulations associated with CAD and with HIV/TB, offering mechanistic insights that may support the development of precision biomarkers and immune-targeted therapies across these disease contexts.

Persistent systemic inflammation is associated with an elevated risk of cardiometabolic diseases. However, the characteristics of the innate and adaptive immune systems in individuals who develop these conditions remain poorly defined. Doublets, or cell-cell complexes, are routinely eliminated from flow cytometric and other immune phenotyping analyses, which limits our understanding of their relationship to disease states. Using well-characterized clinical cohorts, including participants with controlled human immunodeficiency virus (HIV) as a model for chronic inflammation and increased immune cell interactions, we show that circulating CD14+ monocytes complexed to CD3+ T cells are dynamic, biologically relevant, and increased in individuals with diabetes after adjusting for confounding factors. The complexes form functional immune synapses with increased expression of proinflammatory cytokines and greater glucose utilization. Furthermore, in persons with HIV, the CD3+ T cell: CD14+ monocyte complexes had more HIV copies compared to matched CD14+ monocytes or CD4+ T cells alone. Our results demonstrate that circulating CD3+ T-cell: CD14+ monocyte pairs represent dynamic cellular interactions that may contribute to inflammation and cardiometabolic disease pathogenesis. CD3+ T-cell: CD14+ monocyte complexes may originate or be maintained, in part, by chronic viral infections. These findings provide a foundation for future studies investigating mechanisms linking T cell-monocyte cell-cell complexes to developing immune-mediated diseases, including HIV and diabetes.

People living with HIV have a 1.5- to 2-fold increased risk of developing cardiovascular disease. Despite treatment with highly effective antiretroviral therapy, people living with HIV have chronic inflammation that makes them susceptible to multiple comorbidities. Several factors, including the HIV reservoir, coinfections, clonal hematopoiesis of indeterminate potential (CHIP), microbial translocation, and antiretroviral therapy, may contribute to the chronic state of inflammation. Within the innate immune system, macrophages harbor latent HIV and are among the prominent immune cells present in atheroma during the progression of atherosclerosis. They secrete inflammatory cytokines such as IL (interleukin)-6 and tumor necrosis-α that stimulate the expression of adhesion molecules on the endothelium. This leads to the recruitment of other immune cells, including cluster of differentiation (CD)8 + and CD4 + T cells, also present in early and late atheroma. As such, cells of the innate and adaptive immune systems contribute to both systemic inflammation and vascular inflammation. On a molecular level, HIV-1 primes the NLRP3 (NLR family pyrin domain containing 3) inflammasome, leading to an increased expression of IL-1β, which is important for cardiovascular outcomes. Moreover, activation of TLRs (toll-like receptors) by HIV, gut microbes, and substance abuse further activates the NLRP3 inflammasome pathway. Finally, HIV proteins such as Nef (negative regulatory factor) can inhibit cholesterol efflux in monocytes and macrophages through direct action on the cholesterol transporter ABCA1 (ATP-binding cassette transporter A1), which promotes the formation of foam cells and the progression of atherosclerotic plaque. Here, we summarize the stages of atherosclerosis in the context of HIV, highlighting the effects of HIV, coinfections, and antiretroviral therapy on cells of the innate and adaptive immune system and describe current and future interventions to reduce residual inflammation and improve cardiovascular outcomes among people living with HIV.

Chronic inflammation contributes to the prevalence of cardiovascular disease in people living with HIV (PLWH). The immune mechanisms driving atherosclerosis progression in PLWH remain unclear. This study conducted comprehensive assessments of medium-sized coronary arteries and aorta from deceased PLWH and controls without HIV using DNA/RNA assays, spatial transcriptomics, and high-resolution mass spectrometry. Findings revealed more significant inflammation correlated with higher HIV copy numbers in late atheroma of PLWH. Enhanced CXCL12 and decreased ABCA1/ABCG1 expression in CD163+ macrophages were co-localized in coronaries of PLWH, suggesting a reduction in plasma lipoprotein clearance compared to controls. Spatial analyses identified potential therapeutic targets by revealing inflammatory changes in medium-sized arteries and the aorta. We examined the relationship between atherosclerotic phenotypes and inflammatory gene expression in Vanderbilts Biobank to study these findings in a larger clinical cohort. This established a significant association between ABCA1 and CXCL12 gene expressions with atherosclerosis, partly influenced by HIV.

An increased risk of cardiometabolic disease accompanies persistent systemic inflammation. Yet, the innate and adaptive immune system features in persons who develop these conditions remain poorly defined. Doublets, or cell-cell complexes, are routinely eliminated from flow cytometric and other immune phenotyping analyses, which limits our understanding of their relationship to disease states. Using well-characterized clinical cohorts, including participants with controlled HIV as a model for chronic inflammation and increased immune cell interactions, we show that circulating CD14+ monocytes complexed to CD3+ T cells are dynamic, biologically relevant, and increased in individuals with diabetes after adjusting for confounding factors. The complexes form functional immune synapses with increased expression of proinflammatory cytokines and greater glucose utilization. Furthermore, in persons with HIV, the CD3+T-cell: CD14+monocyte complexes had more HIV copies compared to matched CD14+ monocytes or CD4+ T cells alone. Our results demonstrate that circulating CD3+T-cell:CD14+monocyte pairs represent dynamic cellular interactions that may contribute to inflammation and cardiometabolic disease pathogenesis and may originate or be maintained, in part, by chronic viral infections. These findings provide a foundation for future studies investigating mechanisms linking T cellmonocyte cell-cell complexes to developing immune-mediated diseases, including HIV and diabetes.

Chronic systemic inflammation contributes to a substantially elevated risk of myocardial infarction in people living with HIV (PLWH). Endothelial cell dysfunction disrupts vascular homeostasis regulation, increasing the risk of vasoconstriction, inflammation, and thrombosis that contribute to cardiovascular disease. Our objective was to study the effects of plasma from PLWH on endothelial cell (EC) function, with the hypothesis that cytokines and chemokines are major drivers of EC activation. We first broadly phenotyped chemokine and cytokine receptor expression on arterial ECs, capillary ECs, venous ECs, and vascular smooth muscle cells (VSMCs) in adipose tissue in the subcutaneous adipose tissue of 59 PLWH using single cell transcriptomic analysis. We used CellChat to predict cell-cell interactions between ECs and other cells in the adipose tissue and Spearman correlation to measure the association between ECs and plasma cytokines. Finally, we cultured human arterial ECs (HAECs) in plasma-conditioned media from PLWH and performed bulk sequencing to study the direct effects ex-vivo. We observed that arterial and capillary ECs expressed higher interferon and tumor necrosis factor (TNF) receptors. Venous ECs had more interleukin (IL)-1R1 and ACKR1 receptors, and VSMCs had high significant IL-6R expression. CellChat predicted ligand-receptor interactions between adipose tissue immune cells as senders and capillary ECs as recipients in TNF-TNFRSF1A/B interactions. Chemokines expressed largely by capillary ECs were predicted to bind ACKR1 receptors on venous ECs. Beyond the adipose tissue, the proportion of venous ECs and VSMCs were positively plasma IL-6. In ex-vivo experiments, HAECs cultured with plasma-conditioned media from PLWH expressed transcripts that enriched for the TNF-α and reactive oxidative phosphorylation pathways. In conclusion, ECs demonstrate heterogeneity in cytokine and chemokine receptor expression. Further research is needed to fully elucidate the role of cytokines and chemokines in EC dysfunction and to develop effective therapeutic strategies.

Prevalence of hypertension (HTN) and human immunodeficiency virus (HIV) are high among men while screening rates are low. Assisted partner notification service is a strategy recommended by the World Health Organization that aims to increase HIV testing and treatment uptake and may present an opportunity to offer integrated HIV/HTN screening and treatment services. In this prospective cohort study, we assessed the feasibility of integrating HTN screening for male sexual partners of females newly tested HIV-positive in 10 health facilities in Kenya. Participants were notified of the exposure and offered HIV testing and HTN screening; if they accepted and tested positive for either HTN, HIV, or both, they were referred for care. HTN was defined as systolic blood pressure ≥ 140 mm Hg, diastolic blood pressure ≥ 90, or the use of antihypertensive medication. Among 1313 male partners traced, 99% accepted HIV testing and HTN screening. Overall, 4% were found to have HTN, 29% were in the pre-HTN stage, and 9% were HIV-positive. Only 75% had previously been screened for HTN compared to 95% who had previously tested for HIV. A majority preferred non-facility-based screening. The participants who refused HTN screening noted time constraints as a significant hindrance. HIV and HTN screening uptake was high in this hard-to-reach population of men aged 25 to 50. Although HTN rates were low, an integrated approach provided an opportunity to detect those with pre-HTN and intervene early. Strategic integration of HTN services within assisted partners services may promote and normalize testing by offering inclusive and accessible services to men.

Persons with HIV (PWH) on long-term antiretroviral therapy (ART) have a higher incidence and prevalence of cardiometabolic diseases attributed, in part, to persistent inflammation despite viral suppression. In addition to traditional risk factors, immune responses to co-infections such as cytomegalovirus (CMV) may play an unappreciated role in cardiometabolic comorbidities and offer new potential therapeutic targets in a subgroup of individuals. We assessed the relationship of CX3CR1 + , GPR56 + , and CD57 +/- T cells (termed CGC + ) with comorbid conditions in a cohort of 134 PWH co-infected with CMV on long-term ART. We found that PWH with cardiometabolic diseases (non-alcoholic fatty liver disease, calcified coronary arteries, or diabetes) had higher circulating CGC + CD4 + T cells compared to metabolically healthy PWH. The traditional risk factor most correlated with CGC + CD4 + T cell frequency was fasting blood glucose, as well as starch/sucrose metabolites. While unstimulated CGC + CD4 + T cells, like other memory T cells, depend on oxidative phosphorylation for energy, they exhibited higher expression of carnitine palmitoyl transferase 1A compared to other CD4 + T cell subsets, suggesting a potentially greater capacity for fatty acid β-oxidation. Lastly, we show that CMV-specific T cells against multiple viral epitopes are predominantly CGC + . Together, this study suggests that among PWH, CGC + CD4 + T cells are frequently CMV-specific and are associated with diabetes, coronary arterial calcium, and non-alcoholic fatty liver disease. Future studies should assess whether anti-CMV therapies could reduce cardiometabolic disease risk in some individuals.

Abstract Objective Phenotypes and mechanisms of cardiovascular disease (CVD) may differ across global populations. In sub-Saharan Africa (SSA), distinct environmental determinants may influence development and progression of atherosclerotic coronary artery disease (CAD). Methods We investigated associations between 6 established markers of myocardial stress and subsequent subclinical CAD (sCAD), defined as presence of any atherosclerosis on coronary CT angiography (CCTA) in a 2-year prospective cohort of Ugandan adults enriched for cardiometabolic risk factors (RFs) and HIV. Six plasma biomarkers were measured baseline among 200 participants (50% with HIV) aged ≥ 45 years with ≥ 1 cardiovascular RF. At 2-year follow-up, 132 participants (52% with HIV) who returned underwent coronary CCTA. Results In logistic regression models adjusted for cardiovascular RFs (age, diabetes, hypertension, hyperlipidemia, smoking, obesity) and non-traditional RFs (HIV, chronic kidney disease), only NT-proBNP predicted subsequent subclinical CAD (p < 0.008, Bonferroni correction for multiple testing). In sensitivity analyses adjusted for ASCVD risk category (instead of individual RFs) in the baseline cohort with multiple imputation applied to missing year 2 CCTA data (n = 200), NT-proBNP remained significantly associated with subsequent CAD (p < 0.008). Conclusions NT-proBNP consistently predicted subclinical CAD in Uganda in the absence of such an association among other markers of myocardial stress, suggesting a role for NT-proBNP in atherosclerosis independently of coronary microvascular dysfunction.

Introduction HIV and cardiovascular disease (CVD) are the two main causes of death in Kenya with hypertension as CVD’s leading risk factor and HIV infection a risk factor for hypertension. We qualitatively evaluated the feasibility of integrated HIV and hypertension screening at Kenyatta National Hospital. Methods We conducted two focus group discussions (FGDs) in November 2020 (female FGD: n=7; male FGD: n=8) to elicit facilitators, barriers and viability of integrated diagnosis and management of both conditions at HIV testing service (HTS) facilities. Participants were selected using convenience sampling and were not pair matched. All participants had received HTS. All female clients had confirmed hypertension, while male relatives had been contacted for HIV and hypertension screening through a modified assisted partner services model—where a trained healthcare provider supports notification. Transcripts were coded independently, and the codebook was developed and revised through consensus discussion. Data were analysed using thematic content analysis. Results Main barriers to diagnosis and management included limited public awareness of hypertension risk factors and on improved treatment outcomes for those on lifelong HIV treatment, high cost of hypertension care despite free HIV care and healthcare system challenges especially medication stockouts. Strong support systems at family and healthcare levels facilitated care and treatment for both conditions. Participants recommended improved public awareness through individual-level communication and mass media campaigns, decentralised screening services for both HIV and hypertension, and either free or subsidised hypertension care services delivered alongside HIV treatment services. Most felt that an integrated HIV and hypertension service model was viable and would improve healthcare outcomes. Conclusion Patient-centred care models combining HIV and hypertension services hold promise for integrated service delivery.

Objective: Inflammation is key in the pathogenesis of atherosclerotic coronary artery disease (CAD). Distinct sex-specific inflammatory mechanisms may contribute to CAD in sub-Saharan Africa (SSA), where environmental and biological determinants of systemic inflammation may differ from those in high-income settings. Approach and results: We investigated sex differences in inflammatory markers and CAD in a 2-year prospective cohort of Ugandan adults enriched for cardiometabolic risk factors (RFs) and HIV. Seven plasma biomarkers were quantified at the baseline visit among 125 females and 75 males (50% with HIV) at least 45 years old at enrollment with one or more major cardiovascular RF. In year 2, coronary CT angiography (CCTA) was performed in 82 females and 50 males returning for follow-up (52% with HIV). In sex-specific models adjusted for cardiovascular RFs and HIV, tumor necrosis factor-alpha (TNF-α) RII and sCD163 predicted subsequent CAD in females, while only fibrinogen was predictive in males ( P < 0.05). Interleukin-6 (IL-6) and sCD14 were inversely associated with CAD in males ( P < 0.05). Sex modified the associations of TNF-α RII, sCD14, and sCD163 with CAD ( P < 0.05 for interaction). In multivariable multiple imputation models applied to missing year 2 CCTA data to test associations between serum biomarkers in the baseline cohort ( n = 200) and subsequent CAD, higher sCD163 was predictive in females only ( P < 0.05). Conclusions: The positive link between inflammation and subclinical CAD was stronger among females than males in Uganda. Mechanisms by which sex modulates the relationship between inflammation and CAD should be further investigated in SSA.

Background:People who inject drugs (PWID) are disproportionately affected by HIV despite the availability of multiple efficacious biomedical prevention interventions including oral pre-exposure prophylaxis (PrEP). Little is known about the knowledge, acceptability, and uptake of oral PrEP among this population in Kenya. To inform the development of oral PrEP uptake optimization interventions for PWID in Kenya, we conducted a qualitative assessment to establish oral PrEP awareness and willingness to take PrEP by this group in Nairobi City. Methodology:Guided by the Capability, Opportunity, Motivation, and Behaviour (COM-B) model of health behavior change, we conducted 8 focus group discussions (FGDs) among randomly constituted samples of PWID in four harm reduction drop-in centers (DICs) in Nairobi in January 2022. The domains explored were: perceived risks (behaviour), oral PrEP awareness and knowledge (capability), motivation to use oral PrEP (behaviour), and perceptions on community uptake (motivation and opportunity). Completed FGD transcripts were uploaded to Atlas.ti version 9 and thematic analysis was conducted through an iterative process of review and discussion by two coders. Findings:There was a low level of oral PrEP awareness with only 4 of the 46 PWID having heard of PrEP; only 3 out of 46 participants had ever used oral PrEP and 2 out of 3 were no longer using it, indicating a low capacity to make decisions on oral PrEP. Most study participants were aware of the risk posed by unsafe drug injection and expressed willingness to take oral PrEP. Nearly all participants demonstrated low understanding of the role oral PrEP plays in complementing condoms in HIV prevention, presenting an opportunity for awareness creation. While the PWID were eager to learn more about oral PrEP, they favored DICs as places where they would like to obtain information and oral PrEP if they chose to use it, identifying an opportunity for oral PrEP programming interventions. Conclusion:Creation of oral PrEP awareness among PWID in Kenya is likely to improve uptake since the PWID are receptive. Oral PrEP should be offered as part of combination prevention approaches, and effective messaging through DICs, integrated outreaches, and social networks are recommended to mitigate displacement of other prevention and harm reduction practices by this population. Trial Registration:ClinicalTrials.gov Protocol Record STUDY0001370.

Background: Persons with HIV (PWH) on antiretroviral therapy (ART) have persistent immune activation associated with increased risk for non-AIDS related diseases. Latent tuberculosis infection (LTBI), endemic in Africa, may contribute to this immune dysregulation. We evaluated the impact of HIV and TB co-infection on plasma pro- and anti-inflammatory cytokines among Kenyan adults. Methods: We compared data from 221 PWH on long-term ART and 177 HIV-negative adults examining biomarkers of pro-[sCD14, interleukin (IL)-2, IL-6, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-12p70, IL-17A] and anti(IL-4, IL-5, IL-13) inflammatory cytokines, by HIV/LTBI status (HIV+LTBI+, HIV+LTBI−, HIV−LTBI+, HIV−LTBI−). LTBI was diagnosed based on a positive QuantiFERON TB Gold-Plus test in the absence of active TB symptoms. Linear regression was used to evaluate the associations of HIV, LTBI, and HIV/LTBI status with biomarkers adjusting for clinical factors including HIV-specific factors. Results: Half of the participants were women and 52% had LTBI. HIV was independently associated with higher sCD14, IL-15, IL-6, IL-4, IL-5. LTBI was independently associated with higher TNF-α, IL-12p70, IL-17A, IL-4, IL-13 in adjusted models (P < 0.05). LTBI status was associated with higher IL-4 and IL-12p70 only among PWH, but not HIV-negative participants (P < 0.05 for interactions). In multivariate analysis, only HIV+LTBI+ demonstrated elevated levels of TNF-α, IL-6, IL-12p70, IL-15, IL-17A, IL4, IL-5, IL-13 in comparison to the HIV−LTBI− (P < 0.05 for all). The effect of LTBI on cytokines among PWH was independent of CD4+ T-cell count and ART duration. Conclusions: Despite viral suppression, persons with HIV and LTBI exhibit abnormal cytokine production accompanied by high concentrations of pro- and anti-inflammatory cytokines.

Background People living with HIV (PLWH) have a higher risk of developing hypertension compared to HIV uninfected individuals. HIV assisted partner services (aPS), where PLWH are assisted by a healthcare provider to disclose their status to sexual and / or drug injecting partner(s), offers an opportunity for integrated HIV and hypertension screening. We evaluated the feasibility of the aPS model in supporting integrated HIV and hypertension screening at the Kenyatta National Hospital, Kenya. Methods Between August 2019 and December 2020, we conducted a pre-post intervention study. We enrolled women receiving HIV testing services (HTS) with confirmed hypertension (female index clients) and traced their male relatives for HIV and hypertension screening and reviewed management at 3-months. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, and/or use of antihypertensive medication. Results One hundred female index clients (median age: 55 years; interquartile range (IQR): 47–65) mentioned 165 male relatives (median: 49 years; IQR: 40–59) of whom 35% ( n = 58/165) were enrolled. Of the male relatives, 29% had hypertension ( n = 17/58), 34% had pre-hypertension ( n = 20/58), and none were HIV-positive ( n = 0/58). Among the female index clients, there was a statistically significant decline in SBP (pre: 156 mmHg, post: 133 mmHg, p -value: < 0.0001) and DBP (pre: 97 mmHg, post: 80 mmHg, p -value: < 0.0001), and increase in antihypertensive medication uptake (pre: 91%, n = 84/92; post: 98%, n = 90/92; X 2 : 4.3931, p -value: 0.036) relative to baseline. Among the male relatives, there was a statistically significant increase in antihypertensive medication uptake among those with hypertension (pre: 13%, n = 6/46; post: 17%, n = 8/46; X 2 : 32.7750, p -value: < 0.0001) relative to baseline. Conclusion HIV aPS holds promise for integrated HIV and hypertension screening among at-risk clients and their families. Twenty-nine percent of the male relatives had hypertension, higher than the national prevalence (24%), while one-third had pre-hypertension. We observed relatively high participant retention, reductions in blood pressure, and increase in antihypertensive medication uptake among those with confirmed hypertension. Future research expanding the aPS model to other non-communicable diseases through larger studies with longer follow-ups is required to better assess causal relationships and optimize integrated service delivery.

INTRODUCTION:The burden of cardiovascular disease (CVD) is increasing in sub-Saharan Africa with untreated hypertension being a major contributing factor. Understanding the magnitude of the problem and risk factors associated with HIV and long-term antiretroviral therapy (ART) is critically important for designing effective programs for diagnosing and treating hypertension in Kenya. METHODS:In this cross-sectional study, we enrolled 300 persons with HIV (PWH) on long term ART (≥6 months) and 298 HIV-negative adults seeking care at the Kisumu County Hospital between September 2017 and May 2018. Hypertension was defined as blood pressure of ≥140/90mmHg or a previous hypertension diagnosis. Multivariate regression was used to assess the association between hypertension and HIV adjusting for age, sex, and known CVD risk factors. RESULTS:Overall prevalence of hypertension was 22%. PWH had a lower prevalence of hypertension than HIV-negative persons (16% vs 27% respectively; p<0.002). In multivariate analyses, persons with HIV were 37% less likely to have hypertension compared to HIV-negative individuals (adjusted prevalence ratio 0.63; 95% confidence interval: 0.46-0.86). Other factors that were associated with hypertension in all participants included older age >40 years, body mass index (BMI) >25 kg/m2 and low-density lipoproteins ≥130mg/dL. Among PWH, being older than 40 years and higher BMI >30 kg/m2 were associated with hypertension. CONCLUSION:Prevalence of hypertension was high, affecting nearly one in every 4 adults, and associated with older age, higher BMI and high low-density lipoproteins. PWH on long-term ART had significantly lower prevalence of hypertension compared to HIV-negative individuals, potentially due to increased access to healthcare services and interaction with prevention messaging. Interventions to increase screening for and prevention of hypertension in the community for all adults are warranted.

OBJECTIVES:Diastolic dysfunction (DD) has been reported to be highly prevalent in people living with HIV (PLWH) on antiretroviral therapy (ART) leading to the hypothesis that it may be an early marker of myocardial disease. Our objective was to evaluate the prevalence of DD in people living with human immunodeficiency virus without known history of diabetes or hypertension in Western Kenya.METHODS:In this cross-sectional study in western Kenya, 110 PLWH on ART and without known diabetes or hypertension were matched for age ±5 years and sex to HIV-uninfected controls. Study participants underwent a comprehensive two-dimensional echocardiogram and laboratory testing.RESULTS:The mean (SD) age in the HIV-positive group was 42.9 (8.6) years compared with 42.1 (12.9) years in the HIV-uninfected group. Mean (SD) CD4 +T cell count for the HIV-positive group was 557 (220) cells/ml. Mean systolic and diastolic blood pressures were within the normal range and comparable between the two groups. Mean body mass index was 25.2 (5.4) kg/m2 and 26.3 (5.4) kg/m2 in HIV-positive and uninfected participants, respectively. There was only 1 (0.9 %) case of DD in each group. Despite low prevalence of DD, PLWH had 5.76 g/m2 higher left ventricular mass index (p=0.01) and 2.77 mL/m2 larger left atrial volume (p=0.02) compared with the HIV-negative group after adjusting for risk factors associated with DD.CONCLUSION:Contrary to prior reports, DD in PLWH was low. Environmental and cardiovascular disease risk factors such as diabetes and hypertension may be significant modifiers for development and progression of DD in PLWH.

OBJECTIVE:Chronic inflammation contributes to the high burden of cardiovascular disease (CVD) in persons with HIV (PWH). HIV has broad effects on innate and adaptive immune cells, including innate lymphoid cells (ILCs) and CD4+ T-helper cells. At present, the relationship between CVD and plasma cytokines reflecting ILC/T-helper responses in PWH is not well defined. We investigated relationships between plasma cytokines and subclinical atherosclerosis.DESIGN:A cross-sectional study.METHODS:We recruited 70 PWH on a single antiretroviral regimen (efavirenz, teno- fovir, and emtricitabine) with at least 12 months of suppressed viremia and 30 HIVnegative controls. We quantified plasma cytokines and chemokines, including inter- feron-g, interleukin (IL)-4, IL-13, and IL-17A, markers of macrophage activation, and markers of endothelial activation using multiplex assays and ELISA. Cytokines were grouped using Ward's hierarchical clustering. Brachial artery flow-mediated dilation (FMD) and carotid plaque burden were determined using ultrasound. Multivariable linear regression and negative binomial regression analyses were used to assess the relationships of plasma biomarkers and endpoints adjusted for CVD risk factors.RESULTS:We identified three distinct clusters in PWH, one containing Th1/Th2/ILC1/ ILC2 type cytokines, one with Th17/ILC3/macrophage-related cytokines, and a less specific third cluster. Lower FMD was associated with higher plasma IL-17A and macrophage inflammatory protein-1 a. In contrast, IL-4, a Th2/ILC2 type cytokine, was associated with carotid plaque. When HIV-negative controls were added to the models clustering was more diffuse, and these associations were attenuated or absent.CONCLUSION:Th17/ILC3 and Th2/ILC2-mediated immune mechanisms may have distinct roles in endothelial dysfunction and atherosclerotic plaque formation, respectively, in PWH.