Search

Introduction: Perinatally acquired HIV infection (PHIV) occurs during a critical window of immune development. We investigated changes in systemic inflammation and immune activation in adolescents with PHIV and those without HIV (HIV-) in Uganda.. Methods: A prospective observational cohort study was performed in 2017-2021 in Uganda. All participants were between 10-18 years of age and without active co-infections. PHIVs were on ART with HIV-1 RNA level ≤400 copies/mL. We measured plasma and cellular markers of monocyte activation, T-cell activation (expression of CD38 and HLA-DR on CD4+ and CD8+), oxidized LDL, markers of gut integrity and fungal translocation. Groups were compared using Wilcoxon rank sum tests. Changes from baseline were examined with 97.5% confidence intervals on relative fold change. P values were adjusted for false discovery rate.. Results: We enrolled 101 PHIV and 96 HIV-; among these, 89 PHIV and 79 HIV- also had measurements at 96 weeks. At baseline, median (Q1, Q3) age was 13 yrs (11,15), and 52% were females. In PHIV, median CD4+ cell counts were 988 cells/µL (638, 1308), ART duration was 10 yrs (8, 11), and 85% had viral load <50 copies/mL throughout the study, 53% of participants had a regimen switch between visits, 85% of whom switched to 3TC, TDF and DTG. Over 96 weeks, while hsCRP decreased by 40% in PHIV (p=0.12), I-FABP and BDG both increased by 19 and 38% respectively (p=0.08 and ≤0.01) and did not change in HIV- (p≥0.33). At baseline, PHIVs had higher monocyte activation (sCD14) (p=0.01) and elevated frequencies of non-classical monocytes (p<0.01) compared to HIV- which remained stable over time in PHIV but increased by 34% and 80% respectively in HIV-. At both time points, PHIVs had higher T cell activation (p ≤ 0.03: CD4+/CD8+ T cells expressing HLA-DR and CD38). Only in PHIV, at both timepoints, oxidized LDL was inversely associated with activated T cells(p<0.01). Switching to dolutegravir at week 96 was significantly associated an elevated level of sCD163 (β=0.4, 95% CI=0.14,0.57, p<0.01), without changes in other markers.. Conclusion: Ugandan PHIV with viral suppression have some improvement in markers of inflammation over time, however T-cell activation remains elevated. Gut integrity and translocation worsened only in PHIV over time. A deeper understanding of the mechanisms causing immune activation in ART treated African PHIV is crucial. [ABSTRACT FROM AUTHOR]

Background The risk of cardiovascular disease (CVD) and its mechanisms in children living with perinatally acquired HIV (PHIV) in sub-Saharan Africa has been understudied. Methods Mean common carotid artery intima-media thickness (IMT) and pulse-wave velocity (PWV) were evaluated in 101 PHIV and 96 HIV-negative (HIV−) children. PHIV were on ART, with HIV-1 RNA levels ≤400 copies/mL. We measured plasma and cellular markers of monocyte activation, T-cell activation, oxidized lipids, and gut integrity. Results Overall median (interquartile range, Q1–Q3) age was 13 (11–15) years and 52% were females. Groups were similar by age, sex, and BMI. Median ART duration was 10 (8–11) years. PHIV had higher waist–hip ratio, triglycerides, and insulin resistance (P ≤.03). Median IMT was slightly thicker in PHIVs than HIV− children (1.05 vs 1.02 mm for mean IMT and 1.25 vs 1.21 mm for max IMT; P <.05), while PWV did not differ between groups (P =.06). In univariate analyses, lower BMI and oxidized LDL, and higher waist–hip ratio, hsCRP, and zonulin correlated with thicker IMT in PHIV (P ≤.05). After adjustment for age, BMI, sex, CD4 cell count, triglycerides, and separately adding sCD163, sCD14, and hsCRP, higher levels of intestinal permeability as measured by zonulin remained associated with IMT (β = 0.03 and 0.02, respectively; P ≤.03). Conclusions Our study shows that African PHIV have evidence of CVD risk and structural vascular changes despite viral suppression. Intestinal intestinal barrier dysfunction may be involved in the pathogenesis of subclinical vascular disease in this population. [ABSTRACT FROM AUTHOR]

Fatigue and depressive symptoms are prevalent and associated with poor clinical outcomes, though the underlying physiological mechanisms of fatigue and depression are poorly understood. We examined the impact of cardiorespiratory fitness (CRF) on fatigue and depressive symptoms in one-hundred and nine PLHIV. CRF was examined by maximal cardiorespiratory stress test and determined by peak oxygen uptake. Patient-reported fatigue was examined utilizing the HIV-Related Fatigue Scale. Depressive symptoms were examined with the Beck Depression Inventory and PROMISE 29. Data was collected at baseline and six months. Generalized estimating equations were used to determine the effect of CRF on fatigue and depressive symptoms over time. Participants were approximately 53 years old, 86% African American (n = 93), and 65% male (n = 70). After controlling for age and sex, fatigue was inversely associated with CRF (β = −0.163; p =.005). Depressive symptoms were not associated with CRF as measured by the BeckDepression Inventory (p =.587) nor PROMIS 29 (p =.290), but over time, depressive symptoms decreased (p =.051). Increased CRF was associated with decreased fatigue levels, but was not associated with depressive symptoms. These results should guide future research aimed at how CRF might inform interventions to improve fatigue in PLHIV. [ABSTRACT FROM AUTHOR]

Background Children 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. Methods This 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 <400 copies/mL. We measured markers of systemic inflammation, monocyte activation, and gut integrity. Kruskal-Wallis tests were used to compare markers by group and the Spearman correlation was used to assess correlations between biomarkers. Results The 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). Conclusions Despite 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. [ABSTRACT FROM AUTHOR]

People living with HIV (PLHIV) are increasingly diagnosed with comorbidities which require increasing self-management. We examined the effect of a self-management intervention on neurocognitive behavioral processing. Twenty-nine PLHIV completed a two-group, 3-month randomized clinical trial testing a self-management intervention to improve physical activity and dietary intake. At baseline and 3 months later, everyone completed validated assessments of physical, diet, and neurocognitive processing (functional magnetic resonance imaging [fMRI]–derived network analyses). We used linear mixed effects modeling with a random intercept to examine the effect of the intervention. The intervention improved healthy eating (p =.08) but did not improve other self-management behaviors. There was a significant effect of the intervention on several aspects of neurocognitive processing including in the task positive network (TPN) differentiation (p =.047) and an increase in the default mode network (DMN) differentiation (p =.10). Self-management interventions may influence neurocognitive processing in PLHIV, but those changes were not associated with positive changes in self-management behavior. [ABSTRACT FROM AUTHOR]

The mechanisms causing HIV-associated immune activation remain incompletely understood. Alteration of intestinal integrity with subsequent translocation of bacterial products appears to play an important role; however, little is known about the impact of fungal translocation. We assessed the effect of fungal translocation and its association with immune activation in people living with HIV (PLWH) compared with uninfected controls. We measured serum levels of β-D-glucan (BDG) and anti-Saccharomyces cerevisiae antibodies (ASCA) immunoglobulin G (IgG) and immunoglobulin A (IgA) and markers of systemic inflammation and immune activation in virally suppressed PLWH on antiretroviral therapy (ART) and uninfected controls. T-test and Mann–Whitney tests were used to compare markers by HIV status and correlation and regression analyses were used to assess associations of fungal translocation markers with markers of inflammation. One hundred seventy-six participants were included (128 HIV+ and 48 HIV−); 72% male, 65% African American, median age was 50 years, and CD4 was 710 cells/cm3. Levels of BDG tended to be lower in HIV+ when compared with controls (p = .05). No significant difference in levels of ASCA IgG and IgA was seen between groups (p > .75). There was a significant correlation between BDG and several markers of inflammation and immune activation in PLWH, not seen in uninfected controls. In contrast, no correlations were seen between levels of ASCA IgG and IgA with inflammatory markers. PLWH on ART do not have higher levels of BDG or ASCA when compared with uninfected controls, however, the association found between BDG and several inflammation markers suggests a potential role of fungal translocation in the heightened immune activation seen in treated HIV. [ABSTRACT FROM AUTHOR]

We conducted a cross-sectional secondary analysis of baseline data from the SATURN-HIV study ( N = 147; 78% male, 68% Black, median body mass index [BMI] 26.72 kg/m 2 , 13% with osteopenia, HIV-1 RNA < 1,000 copies/mL, stable antiretroviral therapy [ART]) to explore the relationship between physical activity (PA) and bone mineral density (BMD). We measured self-reported minutes of PA and BMD in the overall sample and subgroups based on national recommendations (≥150 minutes/week). Forty-one (28%) participants met recommended PA levels. Higher intensity PA was associated with higher BMD at the total hip ( r = 0.27, p = .09; n = 41; 28%) and lumbar spine ( r = 0.32, p < .05), and predicted higher BMD at the hip ( p < .01; controlling for age, BMI, ART). Lumbar spine BMD did not retain significance in the regression model. Moderate-to-high intensity PA could prevent or mitigate excessive bone loss in people living with HIV. [ABSTRACT FROM AUTHOR]

Background: Lifestyle physical activity (ie, moderate physical activity during routine daily activities most days of the week) may benefit human immunodeficiency virus (HIV)Ypositive adults who are at high risk for cardiovascular disease. Objective: The aims of this study were to describe lifestyle physical activity patterns in HIV-positive adults and to examine the influence of lifestyle physical activity on markers of cardiovascular health. Our secondary objective was to compare these relationships between HIV-positive adults and well-matched HIV-uninfected adults. Methods: A total of 109 HIV-positive adults and 20 control participants wore an ActiGraph accelerometer, completed a maximal graded cardiopulmonary exercise test, completed a coronary computed tomography, completed anthropomorphic measures, and had lipids and measures of insulin resistance measured from peripheral blood. Results: Participants (N = 129) had a mean age of 52 ± 7.3 years, 64% were male (n = 82), and 88% were African American (n = 112). On average, HIV-positive participants engaged in 33 minutes of moderate-to-vigorous physical activity per day (interquartile range, 17-55 minutes) compared with 48 minutes in controls (interquartile range, 30-62 minutes, P = .05). Human immunodeficiency virusYpositive adults had poor fitness (peak oxygen uptake [VO2], 16.8 ± 5.2 mL/min per kg; and a ventilatory efficiency, 33.1 [4.6]). A marker of HIV disease (current CD4+ T cell) was associated with reduced peak VO2 (r = -0.20, P < .05) and increased insulin resistance (r = 0.25, P < .01) but not with physical activity or other markers of cardiovascular health (P ≥ 0.05). After controlling for age, gender, body mass index, and HIV status, physical activity was not significantly associated with peak VO2 or ventilatory efficiency. Conclusion: Human immunodeficiency virusYpositive adults have poor physical activity patterns and diminished cardiovascular health. Future longitudinal studies should examine whether HIV infection blunts the beneficial effects of physical activity on cardiovascular health. [ABSTRACT FROM AUTHOR]

As people living with HIV age, they face increasing self-management work related to HIV infection plus the prevention and mitigation of multiple chronic health conditions, including daily health practices (i.e., physical activity, nutrition), engaging in a supportive community, and accepting the chronicity of HIV. Our purpose was to describe the relationship between HIV self-management practices and mental wellness (depressive symptoms, perceived stress). Ninety-three adult people living with HIV on antiretroviral therapy were enrolled and completed a survey. We used descriptive statistics to summarize variables, and Spearman rank correlation and quantile regression to study associations between variables. Participants’ average age was 48.6 years, 56% were male, and 87% were African American. Daily self-management practices were associated with depressive symptoms ( r = −0.19; p ≤ .01) and perceived stress ( r = −0.14; p = .06); engaging with a supportive community and accepting the chronicity of HIV were not associated with mental wellness (all p > .05). [ABSTRACT FROM AUTHOR]

Purpose: To describe the associations among three social resource variables (social belonging, social support networks, and social capital) and two health promotion behaviors, HIV medication adherence and physical activity, and quality of life among persons living with HIV (PLHIV). Method: We conducted a cross-sectional analysis in 102 adult PLHFV. Social resource variables and quality of life were assessed using validated and widely-used instruments. Physical activity was assessed using a daily physical activity diary and medication adherence was abstracted from the participant's medical record. Spearman correlations and descriptive statistics were used to analyze associations among variables. Results: Fifty-four participants (54%) were male and most were African American (84%), single (69%), and living in poverty (82%). Participants had been living with HIV for an average of 13.6 years (+/- 7) and most were living with at least one non-AIDS comorbidity (80%). Social belonging was significantly associated with HIV medication adherence (ρ = 0.25, p = 0.02), overall functioning (ρ= 0.48, p < 0.01) and life satisfaction quality of life (ρ = 0.50, p< 0.01). Social capital was also associated with HIV medication adherence (ρ = 0.17, p = 0.10) and life satisfaction quality of life (ρ = 0.29, p < 0.01). Conclusions: We found that there are distinctions among various, widely-used social resource constructs. By describing these unique associations and distinctions, our study helps identify which social resources should be targeted in the development of interventions to improve health promotion and the quality of life of members of this marginalized population. [ABSTRACT FROM AUTHOR]

Background Selenium deficiency has been reported to be associated with HIV disease progression and chromium deficiency with insulin resistance and hyperlipidemia. Here, we assessed selenium and chromium status in a cohort of Ugandan HIV+, HIV exposed uninfected (HEU) and HIV negative (HIV−) children and their associations with markers of systemic inflammation, immune activation, and gut integrity. Methods This is a cross-sectional study in HIV+, HEU and HIV unexposed uninfected (HIV-) children aged 2–10 years old enrolled in Uganda. HIV+ children were on stable ART with undetectable viral load. We measured plasma concentrations of selenium and chromium as well as markers of systemic inflammation, monocyte activation, gut integrity and insulin resistance (HOMA-IR). Results Among HIV+ children (n = 57), 93% had viral load ≤ 20 copies/mL, mean CD4 was 34% and 77% were receiving a non-nucleotide reserve transcriptase regimen. Mean age of all participants was 7 years and 55% were girls. Mean selenium concentrations were higher in the HIV+ group (106 µg/L) compared with the HEU (84 µg/L) and HIV− (98 µg/L) groups (p. Mean chromium concentrations were 1 µg/L; 1 HIV+ child and 6 HEU children had chromium levels > 1 µg/L (p. Conclusion In this cohort of HIV+ children on ART in Uganda, plasma selenium and chromium concentrations appear sufficient. Higher plasma selenium concentrations were associated with lower systemic inflammation and higher gut integrity markers. Although our findings do not support the use of selenium supplementation broadly for HIV-infected children in Uganda, further studies are warranted to assess the role of selenium supplements in attenuating heightened inflammation. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background This study was conducted to explore the associations between serum albumin and markers of inflammation and cardiovascular disease in treated human immunodeficiency virus (HIV)-infected adults. Methods We conducted a nested study within in the SATURN-HIV trial in which 147 HIV+ adults on stable antiretroviral therapy were (1) virally suppressed, (2) had a low-density lipoprotein (LDL)-cholesterol level <130 mg/dL, and (3) were randomized to 10 mg daily rosuvastatin or placebo. Measures of serum albumin, carotid intima media thickness ([cIMT] surrogate marker of atherosclerosis), inflammation, T cells, monocyte activation, and gut integrity were assessed at baseline, 48 and 96 weeks later. Spearman correlations and linear mixed-effect models were used to assess associations with serum albumin. Results Mean age was 45 years, 80% of participants were male, and 69% were African American. Mean serum albumin was similar between the groups at all time points (4.01–4.09 g/dL in statin arm vs 4.02–4.11 g/dL in placebo arm; P =.08–0.35). Lower baseline serum albumin significantly predicted larger changes in cIMT, interleukin 6, D-dimer, tumor necrosis factor α receptor 1, fibrinogen, and high-sensitivity C-reactive protein (P ≤.03) over 96 weeks independently of statin therapy. After adjusting for age, gender, smoking, body mass index, creatinine clearance, and LDL cholesterol, every 1 g/dL decrease in serum albumin at baseline remained associated with a 0.05-mm increase in cIMT over 96 weeks (P =.05). Conclusions Lower serum albumin in controlled HIV is associated with higher markers of chronic inflammation and hypercoagulation, which could explain the prior observation that serum albumin predicts nonacquired immune deficiency syndrome events in HIV. Serum albumin may predict progression of carotid atherosclerosis independent of traditional risk factors. [ABSTRACT FROM AUTHOR]

Background and aims Asymmetric dimethylarginine (ADMA) is an inhibitor of nitric oxide and an independent risk factor for cardiovascular disease. We examined the effect of statin on ADMA in HIV + patients on stable ART, and whether such an effect contributes to the favorable changes on carotid intima media thickness. Methods This is a secondary analysis of SATURN-HIV, in which HIV + adults on stable ART with HIV-1 RNA< 1000 copies/mL and LDL-cholesterol <130 mg/dL were randomized to 10 mg daily rosuvastatin or placebo. Arginine metabolites, ADMA, and markers of inflammation were assessed at baseline and 48 weeks. Carotid intima media thickness (c-IMT) was measured at baseline, 48 and 96 weeks. Spearman correlations, and linear mixed-effect models were used to study relationships among variables. Results Overall, 79% were male, 68% African Americans, with a median age of 46 years. In the statin arm, no change in ADMA levels was observed at 48 weeks (0.70%), whereas a trend towards an increase in ADMA levels (23.78%) was observed in the placebo group ( p = 0.06). Elevated baseline ADMA (highest tertile) was associated with a 0.04 mm increase in c-IMT ( p = 0.03) after adjusting for statin and study duration. No interaction was seen between baseline ADMA and statin randomization on change in c-IMT ( p = 0.21). Conclusions In HIV + subjects on ART, rosuvastatin suppressed the increase over time in ADMA levels. Elevated baseline levels of ADMA were associated with increases in c-IMT, regardless of statin assignment. The favorable effect of rosuvastatin on c-IMT appears to be independent of the arginine pathway. [ABSTRACT FROM AUTHOR]

Objective: In this study, we explored the effect of zinc supplementation on markers of inflammation and monocyte activation in antiretroviral therapy--treated HIV infection. Methods: This is a phase I open-labeled randomized double-arm study, exploring the efficacy and safety of zinc supplementation on inflammation in ≥18-year-old people living with HIV in the US, on stable antiretroviral therapy and with zinc levels ≤75 µg/dL in the last 60 days. Patients were randomized 1:1 to zinc gluconate capsules at a dose of 45 µg (low-dose), or 90 mg (high-dose) elemental zinc daily for 16 weeks. We assessed inflammatory and gut integrity biomarkers at baseline and 16 weeks. Results: Overall, a total of 52 participants were enrolled (25 participants in the low-dose arm and 27 participants in the high-dose arm). Median (Interquartile range) age was 49 (38, 60) years, 77% were men and 73% were African Americans. At baseline, median zinc levels were 73 (64, 86) µg/dL. Median circulating zinc levels increased to 91 µg/dL in the low-dose arm and to 100 µg/dL in the high-dose arm. Overall, 48%-60% of participants experienced a reduction in biomarkers levels. The margin of reduction ranged between 8% and 21%. This change was meaningful with large effect size (Cohen D ranging from 5 to 19). Conclusions: In this pilot study, we found that zinc supplementation is effective at increasing circulating zinc levels. In addition, our findings provide novel data suggesting that zinc can affect a biological signature in people living with HIV and modulate biomarkers associated with clinical comorbidities. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of a lifestyle behavior intervention (SystemCHANGE) on physical activity and diet quality among sedentary people living with HIV (PLHIV). All participants expressed a desire to improve lifestyle health behaviors. Methods: One hundred and seven HIV+ adults were randomized to either the intervention (6, in-person, standardized group sessions focusing on improving lifestyle behaviors) or a control condition (general advice on AHA diet and exercise guidelines). All participants wore an ActiGraph accelerometer and completed 24-hour dietary recalls at baseline, 3, and 6 months. Generalized estimating equations were used to examine intervention effects. The primary activity outcome was time spent in moderate-to-vigorous physical activity, and the primary dietary outcome was Healthy Eating Index. Results: Mean age was 53 years, 65% were male, and 86% African American. Approximately 90% attended at least half of the sessions and 60% attended 5 or more sessions. The intervention did not significantly improve our primary lifestyle behavior endpoints (P ≥ 0.05); however, intervention participants consumed fewer carbohydrates--primarily sugar-sweetened beverages--per day and lost 0.732 kg body weight compared with a 0.153 weight gain in the control group (P = 0.03). Conclusions: Among sedentary PLHIV at high risk of cardiovascular disease, the SystemCHANGE intervention reduced daily carbohydrate intake and body weight, but did not increase physical activity or improve overall diet quality. Future work should identify fundamental personal, interpersonal, and contextual factors that will increase physical activity and improve overall diet quality among this population, and integrate these factors into tailored, lifestyle interventions for aging PLHIV. [ABSTRACT FROM AUTHOR]

Background: People living with HIV (PLHIV) are at increased risk for cardiovascular disease (CVD). Maximal cardiorespiratory fitness (CRF) is a better predictor of CVD-related mortality than established risk factors. Yet very little is known about CRF in PLHIV and even less is known about how to improve CRF in PLHIV in real world settings. Objective: To examine the effect of a lifestyle exercise and diet intervention in PLHIV, and to examine predictors of change in CRF over six months. Methods: One-hundred and six virally suppressed PLHIV, were randomized to either the intervention (six, standardized group sessions focusing on improving lifestyle behaviors) or the control condition (general diet and exercise advice). All participants completed a maximal cardiorespiratory stress test on a cycle ergometer to determine VO2 peak, VE/VCO2, and VO2 at anaerobic threshold at baseline and six months later. Participants also wore an ActiGraph accelerometer to measure physical activity, completed hip-waist circumference measures, and had a fasting lipid profile, interleukin-6, and hsCRP. Generalized estimating equations were used to examine the effect of the intervention on CRF and predictors of change in CRF. Results: Participants were approximately 53 years old, 65% male (n =70), 86% African American (n =93) and had a current CD4+ T cell count of 671 cells/μL. There was no effect of the intervention on markers of CRF over time (p>0.05). After controlling for age, gender, waist-hip-ratio, a change in IL-6 was inversely associated with change in both VO2peak (p =0.03) and VO2 at anaerobic threshold (p =0.03) (Table 1). Additionally, controlling for age, gender, and waist-hip-ratio, steps taken per day were associated with higher VO2 peak. Over the duration of the 6-month study, participants who engaged in the recommended 10,000 steps per day had a 2.69 ml/kg/min higher VO2 peak (p =0.02). Conclusions: Despite HIV viral suppression, markers of inflammation were associated with a clinically adverse CRF profile in this older HIV+ cohort. However, increased physical activity was associated with improved CRF. Future research understanding how IL-6 might inform treatment goals and improving physical activity in PLHIV is warranted. [ABSTRACT FROM AUTHOR]