Combination Antiretroviral Therapy Is Associated With Reduction in Liver Fibrosis Scores in HIV-1-Infected Subjects

HIV increases the risk of liver disease as do two common coinfections, hepatitis B and C viruses (HBV and HCV). However, whether combination antiretroviral therapy (cART) reverses or exacerbates hepatic fibrosis remains unclear.This was an observational retrospective study. cART-naïve HIV-infected subjects without a history of substance abuse (including alcohol) had liver disease stage determined by aspartate aminotransferase-to-platelet ratio indices (APRIs) and fibrosis-4 (FIB-4) before and 24 and 48 weeks after cART. All the data were retrieved from previously established cohorts. Values before and after cART were compared using Wilcoxon test for paired samples. Regression analyses were used to determine factors associated with moderate-to-severe liver disease.Of the 1105 HIV-infected subjects, 120 were HBV coinfected and 64 were HCV coinfected. About 20% of HIV monoinfected participants had APRI and FIB-4 scores consistent with moderate-to-significant fibrosis compared to ∼36% of HIV–HBV coinfected and 67% to 77% of HIV–HCV coinfected participants. In adjusted analyses compared with HIV monoinfection, HBV coinfection was associated with 1.18-fold higher APRI (P < 0.001) and a 1.12-fold higher FIB-4 (P = 0.007) prior to cART; while HCV coinfection was associated with 1.94-fold higher APRI (P < 0.001) and a 1.43-fold higher FIB-4 (P < 0.001). After 48 weeks of cART, both fibrosis scores decreased in all subjects; however, HCV coinfection was still associated with higher fibrosis scores at week 48 compared to HIV monoinfection.cART was associated with improvement in hepatic fibrosis scores in the majority of HIV-hepatitis coinfected and HIV-monoinfected Chinese participants.     

Liver Fibrosis in HIV Patients Receiving a Modern cART: Which Factors Play a Role?

Liver-related death in human immunodeficiency virus (HIV)-infected individuals is about 10 times higher compared with the general population, and the prevalence of significant liver fibrosis in those with HIV approaches 15%. The present study aimed to assess risk factors for development of hepatic fibrosis in HIV patients receiving a modern combination anti-retroviral therapy (cART).This cross-sectional prospective study included 432 HIV patients, of which 68 (16%) patients were anti-hepatitis C virus (HCV) positive and 23 (5%) were HBsAg positive.Health trajectory including clinical characteristics and liver fibrosis stage assessed by transient elastography were collected at inclusion. Liver stiffness values >7.1 kPa were considered as significant fibrosis, while values >12.5 kPa were defined as severe fibrosis. Logistic regression and Cox regression uni- and multivariate analyses were performed to identify independent factors associated with liver fibrosis.Significant liver fibrosis was detected in 10% of HIV mono-infected, in 37% of HCV co-infected patients, and in 18% of hepatitis B virus co-infected patients. The presence of diabetes mellitus (odds ratio [OR] = 4.6) and FIB4 score (OR = 2.4) were independently associated with presence of significant fibrosis in the whole cohort. Similarly, diabetes mellitus (OR = 5.4), adiposity (OR = 4.6), and the FIB4 score (OR = 3.3) were independently associated with significant fibrosis in HIV mono-infected patients. Importantly, cumulative cART duration protected, whereas persistent HIV viral replication promoted the development of significant liver fibrosis along the duration of HIV infection.Our findings strongly indicate that besides known risk factors like metabolic disorders, HIV may also have a direct effect on fibrogenesis. Successful cART leading to complete suppression of HIV replication might protect from development of liver fibrosis.     

HIV viral exposure and mortality in a multicenter ambulatory HIV adult cohort,United States, 1995–2016

The aim of this study was to identify viral exposure (VE) measures and their relationship to mortality risk among persons with HIV.Prospective multicenter observational study to compare VE formulae.Eligible participants initiated first combination antiretroviral therapy (cART) between March 1, 1995 and June 30, 2015. We included 1645 participants followed for ≥6 months after starting first cART, with cART prescribed ≥75% of time, who underwent ≥2 plasma viral load (VL) and ≥1 CD4+ T-lymphocyte cell (CD4) measurement during observation. We evaluated all-cause mortality from 6 months after cART initiation until June 30, 2016. VE was quantified using 2 time-updated variables: viremia copy-years and percent of person-years (%PY) spent >200 or 50 copies/mL. Cox models were fit to estimate associations between VE and mortality.Participants contributed 10,453 person years [py], with median 14 VLs per patient. Median %PY >200 or >50 were 10% (interquartile range: 1%–47%) and 26% (interquartile range: 6%–72%), respectively. There were 115 deaths, for an overall mortality rate of 1.19 per 100 person years. In univariate models, each measure of VE was significantly associated with mortality risk, as were older age, public insurance, injection drug use HIV risk history, and lower pre-cART CD4. Based on model fit, most recent viral load and %PY >200 copies/mL provided the best combination of VE factors to predict mortality, although all VE combinations evaluated performed well.The combination of most recent VL and %PY >200 copies/mL best predicted mortality, although all evaluated VE measures performed well.     

Duration of antiretroviral therapy among people living with HIV and incidence of hypertension in Ghana

Understanding the differential rates of incident hypertension among People Living with HIV (PLWH) based of duration of exposure to combination antiretroviral therapy (cART) may provide insights into the pathogenesis of hypertension in this population. Utilizing the dataset of a prospective study conducted at a Ghanaian tertiary medical center, we evaluated factors associated with incident hypertension among PLWH previously naïve to cART before study enrollment (cART newly prescribed group, n = 221) versus PLWH established on cART for at least a year (cART established group, n = 212). New‐onset hypertension was diagnosed as clinic BP > 140/90 mmHg on two separate clinic visits over 12‐month follow‐up. Cox proportional hazards regression models were used to assess factors associated with incident hypertension. Mean age of new versus cART established was 41.1 ± 8.2 versus 45.1 ± 8.6 years (p < .001), with more women in the cART established group (68.3 vs. 82%, p = .0009). There were 105 (24.3%) episodes of incident hypertension over 328 person‐years follow‐up (PYFU), incidence rate of 320.1 (95% CI: 263.1‐385.9)/1000 PYFU, with higher rates in new versus cART established (476.6/1000 PYFU vs. 222.8/1000 PYFU, p = 0.0002). Overall, age by increasing decile (aHR 0.76; 95% CI: 0.59‐0.98), log HIV‐1 viral load (aHR 1.16; 1.04‐1.35), and use of tenofovir (aHR 1.66; 1.04‐2.64) were associated with incident hypertension. While CD4 counts, age, BMI, pre‐diabetes, and urban/peri‐urban residency were independently associated with hypertension in the cART established group; no independent predictors were identified among the cART newly prescribed group. Further studies to explore the potential mechanisms underlying incidence of hypertension in PLWH are warranted.     

Predictors of low ovarian reserve in cART-treated women living with HIV

Ovarian dysfunction and lower circulating anti-Müllerian hormone (AMH) feature women living with HIV (WLWH). Because treated human immunodeficiency virus (HIV) infection is characterized by a pro-inflammatory/oxidative phenotype resulting in residual comorbidity, we sought to investigate possible associations between plasma AMH and markers of inflammation, immune activation/senescence/exhaustion, oxidative stress as well as comorbidities in a cohort of combined anti-retroviral therapy (cART)-treated WLWH versus age-matched HIV-uninfected, healthy women.Eighty WLWH on effective cART aged 25 to 50 years and 66 age-matched healthy women were enrolled. We measured: plasma AMH, IL-6, reactive oxygen species modulator 1 (ROMO1) (ELISA); plasma tumor necrosis factor α, IL-10, soluble vascular cell adhesion molecule 1, osteopontin (Luminex); CD4/CD8 activation (CD38/CD69), apoptosis (CD95), exhaustion (PD1), maturation (CD45RA/CD45R0/CD127/CCR7), recent thymic emigrants (CD31/CD103) (flow cytometry). Mann Whitney and chi-squared tests were used. Univariate and multivariate logistic regression analyses were used to assess factors associated with low AMH (≤1 ng/mL).Compared to healthy women, WLWH were more frequently non-Caucasian, drug/alcohol abusers, with history of late menarche, lower hormonal contraceptive use, with higher gravidity and lower parity. WLWH showed significantly lower AMH (P = .004) as well as higher ROMO1 (P = .0003) and tumor necrosis factor α (P < .0001). The multivariate analyses revealed ROMO1 (adjusted odds ratio [AOR]: 1.42, P = .03) and HIV infection (AOR: 8.1, P = .0001) as independently associated with low AMH. The logistic regression model with both HIV status and ROMO1 (a marker of oxidative stress) confirmed HIV as the only predictor of low AMH (AOR: 17, P = .0003).Despite effective cART, WLWH showed lower AMH compared to age-matched peers, indicating pre-mature ovarian ageing. Both HIV and oxidative stress are independently associated with low AMH, emphasizing the impact of HIV-associated oxidative stress on reproductive aging.     

Effects of perinatal HIV-infection on the cortical thickness and subcortical gray matter volumes in young adulthood

Brain atrophy has been observed in perinatally HIV-infected patients (PHIV) despite initiation on combined antiretroviral treatment (cART), but neuroimaging studies are limited. We aimed to evaluate cortical thickness (CT) and subcortical gray matter (GM) volumes of PHIV youths with stable immunovirological situation and with a normal daily performance.A prospective cross-sectional study was conducted. A total of 25 PHIV patients on cART and 25 HIV-negative (HIV-) controls matched by age, sex, level of education, and socioeconomic status underwent a magnetic resonance imaging scan. CAT12 toolbox was used to extract CT values from T1w images using parcellations from Desikan–Killiany atlas (DK40). To measure regional brain volumes, native segmented images were parceled in regions of interest according to the Neuromorphometrics Atlas. Neuropsychological assessment and psychopathological symptoms were documented.Fifty participants were included (60% females, median age 20 years [interquartile range, IQR 19–23], 64% Whites). No differences regarding neuropsychological tests or psychopathological symptoms were found between groups (all P > .05). All participants presented an average performance in the Fluid Intelligence (FI) test (PHIV mean: −0.12, HIV- mean: 0.24), When comparing CT, PHIV-infected patients showed thinner cortices compared with their peers in fusiform gyrus (P = .000, P = .009), lateral-orbitofrontal gyrus (P = .006, P = .0024), and right parsobitalis gyrus (P = .047). Regarding subcortical GM volumes, PHIV patients showed lower right amygdala (P = .014) and left putamen (P = .016) volumes when compared with HIV- controls. Within the PHIV group, higher CD4 count was associated with higher volumes in right putamen (B = 0.00000038, P = .045). Moreover, increased age at cART initiation and lower nadir CD4 count was associated with larger volumes in left accumbens (B = 0.0000046, P = .033; B = −0.00000008, P = .045, respectively).PHIV patients showed thinner cortices of areas in temporal, orbito-frontal and occipital lobes and lower volumes of subcortical GM volumes when compared with the HIV- control group, suggesting cortical and subcortical brain alterations in otherwise neuroasymptomatic patients. Nevertheless, larger and longitudinal studies are required to determine the impact of HIV on brain structure in PHIV patients and to further identify risk and protective factors that could be implicated.     

Serum Gamma-Glutamyltransferase Levels are Associated With Concomitant Cardiovascular Risk Factors in Korean Hypertensive Patients: A Nationwide Population-Based Study

Previous studies suggested that serum gamma-glutamyltransferase (GGT) levels were associated with the prevalence of cardiovascular disease (CVD) risk factors including hypertension, diabetes mellitus (DM), and metabolic syndrome (MetS) in the general population. We aimed to investigate the relationship between serum GGT levels and CVD risk factors in Korean hypertensive patients.This cross-sectional study was based on data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2011 to 2012. The analysis included 1541 hypertensive participants. Study participants were divided into groups according to tertiles of serum GGT with cutoff points of 20 and 35 U/L.Serum GGT levels were positively associated with the components of MetS (P value < 0.05, except for systolic blood pressure and high-density lipoprotein cholesterol). After adjusting for possible confounders, serum GGT levels were associated with an increased risk of MetS, high waist circumference, high triglyceride level, fasting plasma glucose, DM, and the urinary albumin-to-creatinine ratio (P = 0.001).In hypertensive patients, serum GGT levels are positively associated with major cardiovascular risk factors such as MetS, DM, and urinary albumin excretion.     

Inequalities in Cardiovascular Health Between Local and Migrant Residents: A Cross-Sectional Study of 6934 Participants in Longhua District,Shenzhen

Household registration status is one social determinant that influences health disparities. This study aimed to investigate the disparities in cardiovascular health between local and migrant residents, which may provide important implications for public health services and may help improve cardiovascular health for residents in Shenzhen.A cross-sectional study was conducted in Shenzhen City Longhua district. Participants were selected for face-to-face interview surveys by using a multistage cluster random sampling design. Chi-square tests and multiple logistic regression models were constructed to compare cardiovascular health between the migrant and local residents.A total of 6934 eligible respondents, of whom 1400 were local and 5534 were migrants, completed the face-to-face interview surveys. The local residents were more likely to have hypertension (3.1% vs. 2.0%, P < 0.05) and diabetes mellitus (1.4% vs. 0.5%, P < 0.05), whilst to be overweight or obese (20.3% vs. 16.4%, P < 0.05) when compared with their migrant counterparts. A higher proportion of local residents than migrant ones had ≥2 cardiovascular risk factors, 2.4% and 1.2%, respectively (P < 0.01). Compared with migrants, the locals were more likely to know their BP values (65.4% vs. 54.5%, P < 0.05) and know the symptoms of diabetes (63.1% vs. 49.7%, P < 0.01).Our study suggests that household registration status is an important driver of social disparities in cardiovascular health except for the factors regarding socioeconomic status. Programs to improve the awareness of hypertension and diabetes are suggested to be initiated among the migrants.     

Hospitalization for Pneumonia is Associated With Decreased 1-Year Survival in Patients With Type 2 Diabetes: Results From a Prospective Cohort Study

Diabetes mellitus is a frequent comorbid conditions among patients with pneumonia living in the community.The aim of our study is to evaluate the impact of hospitalization for pneumonia on early (30 day) and late mortality (1 year) in patients with type 2 diabetes mellitus.Prospective comparative cohort study of 203 patients with type 2 diabetes hospitalized for pneumonia versus 206 patients with diabetes hospitalized for other noninfectious causes from January 2012 to December 2013 at Policlinico Umberto I (Rome). Enrolled patients were followed up to discharge and up to 1 year after initial hospital admission or death.Overall, 203 patients with type 2 diabetes admitted to hospital for pneumonia were compared to 206 patients with type 2 diabetes admitted for other causes (39.3% decompensated diabetes, 21.4% cerebrovascular diseases, 9.2% renal failure, 8.3% acute myocardial infarction, and 21.8% other causes). Compared to control patients, those admitted for pneumonia showed a higher 30-day (10.8% vs 1%, P < 0.001) and 1-year mortality rate (30.3% vs 16.8%, P < 0.001). Compared to survivors, nonsurvivor patients with pneumonia had a higher incidence of moderate to severe chronic kidney disease, hemodialysis, and malnutrition were more likely to present with a mental status deterioration, and had a higher number of cardiovascular events during the follow-up period. Cox regression analysis found age, Charlson comorbidity index, pH < 7.35 at admission, hemodialysis, and hospitalization for pneumonia as variables independently associated with mortality.Hospitalization for pneumonia is associated with decreased 1-year survival in patients with type 2 diabetes, and appears to be a major determinant of long-term outcome in these patients.     

Obesity and risk for hypertension and diabetes among Kenyan adults: Results from a national survey

Despite the anticipated growth in the global burden of obesity especially in low-income countries, limited data exist on the contribution of obesity to cardiometabolic diseases in Africa.We examined population-based samples of Kenyan adults who participated in the 2015 national chronic disease risk factor surveillance survey. Weight and height were measured, and body mass index (BMI) was calculated and used as a measure for general obesity. Waist circumference (WC), a clinical measure of central obesity was also measured. Logistic regression was used to assess the association between obesity with hypertension, diabetes, and dyslipidemia risk.Of the 4276 participants, the median (IQR) age was 36 (27–47) years, 41% were men. One-third (37%) of the participants were centrally obese, whereas 10% were generally obese. The odds for overweight and general obesity were highest among females, adults >40 years, and those in the highest wealth quartile. Central and general obesity, assessed by WC and BMI, were associated with hypertension and dyslipidemia but not diabetes for both sexes. Compared with adults of normal weight, individuals with a BMI of ≥30 kg/m² had an odds ratio of 2.39 (95% confidence interval [CI], 1.82–3.12) for hypertension and 2.24 (95% CI, 1.70–2.96) for dyslipidemia.Obesity prevalence is high in Kenya and is associated with hypertension and dyslipidemia but not diabetes. Our findings indicate an urgent need to develop public health interventions to address obesity and prevent the development of comorbid conditions.     

Prevalence and risk of residual viremia after ART in low- and middle-income countries: A cross-sectional study

In order to design effective strategies to eradicate the HIV, an understanding of persistent viral reservoirs is needed. Many studies have demonstrated HIV residual viremia prevalence in high income countries, data from low- and middle-income countries (LMIC) are limited. We assessed the prevalence, and factors associated with residual viremia in people with HIV (PWH), who were virally-suppressed on antiretroviral therapy (ART) in LMIC. We also compared residual viremia prevalence between the LMIC and US.This is a cross-sectional, retrospective study that utilized stored specimen samples from the AIDS clinical trials group (ACTG) studies A5175 and A5208. The last available sample among participants with plasma HIV RNA < 400 copies/mL for ≥3 years were tested by the HIV molecular and monitoring core gag (HMMCgag) single copy assay (SCA). Residual viremia was defined as detectable if ≥1 copy/mL. Spearman''s correlation and multivariable stepwise logistic regression were used to assess associations of various factors with SCA.A total of 320 participants, 246 (77%) from LMIC and 74 (23%) from US, were analyzed. Median (IQR) age was 33 (2840) years; baseline CD4 166 (88,230) cells/mm³; HIV RNA 5.0 (4.5, 5.3) log10 copies/mL; duration of viral suppression 3.4 (3.1, 4.0) years and 48% were male. In 85 participants with information available, 53% were subtype C, 42% subtype B and 5% other subtypes. Overall prevalence of residual viremia was 57% [95% CI, 52–63] with 51% [40–63] in US and 59% [53–65] in LMIC. Among participants with detectable SCA, the median (IQR) HIV RNA was 3.8 (2.2, 8.1) copies/mL. The multivariable model conducted in LMIC participants showed that higher baseline HIV RNA was associated with detectable residual RNA (OR 2.9, 95% CI 1.8, 4.6 for every log10 increase, P < .001). After including both US and LMIC in the final model, baseline HIV RNA remained significant. No difference in SCA detestability was found between US and LMIC sites (OR 1.1 [0.6, 2.0], P = .72) after adjusting for baseline RNA and parent study.The prevalence of residual viremia between both groups were not different and more than half of the participants had detectable viremia. Higher baseline HIV RNA was independently associated with residual viremia.     

Association of blood cobalt concentrations with dyslipidemia,hypertension, and diabetes in a US population: A cross-sectional study

Various heavy metal elements in the human body have been reported to be associated with dyslipidemia, hypertension, and diabetes. The role of cobalt in these conditions is unclear. The current study aimed to investigate the association of blood cobalt concentrations with dyslipidemia, hypertension, and diabetes.Using the data collected from the National Health and Nutrition Examination Survey (2015-2018), we performed logistic regression to explore the association of blood cobalt concentrations with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, hypertension, and diabetes.A total of 6866 adults were included in this study. Participants with higher blood cobalt levels appeared to be older and have a lower body mass index and, were more likely to be female (P for trend < .05). After fully adjusting for demographic characteristics (Model 2), compared with the lowest quartile, the highest quartile of blood cobalt concentrations had lower odds ratios (ORs) for elevated TC [OR: 0.62, 95% confidential interval (CI): 0.53 to 0.72, P < .001], elevated LDL-C (OR: 0.65, 95% CI: 0.53-0.80, P < .001) and low HDL-C (OR: 0.81, 95% CI: 0.69-0.96, P = .013). The adjusted ORs for elevated TC, elevated LDL-C and low HDL-C were negatively correlated with increased blood cobalt concentrations (P for trend < .05). The adjusted ORs for hypertension and diabetes were not associated with blood cobalt concentrations (P > .05 and P for trend > .05).In conclusion, higher blood cobalt concentrations were associated with a lower risk of dyslipidemia. However, blood cobalt concentrations were not associated with the risk of hypertension or diabetes.     

Factors Associated With High Sodium Intake Based on Estimated 24-Hour Urinary Sodium Excretion: The 2009–2011 Korea National Health and Nutrition Examination Survey

Although reducing dietary salt consumption is the most cost-effective strategy for preventing progression of cardiovascular and renal disease, policy-based approaches to monitor sodium intake accurately and the understanding factors associated with excessive sodium intake for the improvement of public health are lacking.We investigated factors associated with high sodium intake based on the estimated 24-hour urinary sodium excretion, using data from the 2009 to 2011 Korea National Health and Nutrition Examination Survey (KNHANES).Among 21,199 adults (≥19 years of age) who participated in the 2009 to 2011 KNHANES, 18,000 participants (weighted n = 33,969,783) who completed urinary sodium and creatinine evaluations were analyzed in this study. The 24-hour urinary sodium excretion was estimated using Tanaka equation.The mean estimated 24-hour urinary sodium excretion level was 4349 (4286–4413) mg per day. Only 18.5% (weighted n = 6,298,481/3,396,973, unweighted n = 2898/18,000) of the study participants consumed less the 2000 mg sodium per day. Female gender (P < 0.001), older age (P < 0.001), total energy intake ≥50 percentile (P < 0.005), and obesity (P < 0.001) were associated with high sodium intake, even after adjusting for potential confounders. Senior high school/college graduation in education and managers/professionals in occupation were associated with lower sodium intake (P < 0.001). According to hypertension management status, those who had hypertension without medication consumed more sodium than those who were normotensive. However, those who receiving treatment for hypertension consumed less sodium than those who were normotensive (P < 0.001). The number of family members, household income, and alcohol drinking did not affect 24-hour urinary sodium excretion. The logistic regression analysis for the highest estimated 24-hour urinary sodium excretion quartile (>6033 mg/day) using the abovementioned variables as covariates yielded identical results.Our data suggest that age, sex, education level, occupation, total energy intake, obesity, and hypertension management status are associated with excessive sodium intake in Korean adults using nationally representative data. Factors associated with high sodium intake should be considered in policy-based interventions to reduce dietary salt consumption and prevent cardiovascular disease as a public health target.     

A Taiwanese Nationwide Cohort Study Shows Interferon-Based Therapy for Chronic Hepatitis C Reduces the Risk of Chronic Kidney Disease

Hepatitis C virus (HCV) infection is a risk factor for chronic kidney disease (CKD). However, it remains unclear whether interferon-based therapy (IBT) for HCV was associated with reduced risk of CKD.From the Taiwan National Health Insurance Research Database, we identified 919 patients who received 3 months or more of IBT as our treated cohort. This cohort was propensity score-matched 1:4 with 3676 controls who had never received IBT for HCV infection (untreated cohort). Cumulative incidences of and hazard ratios (HRs) for CKD were calculated after adjusting for competing mortality.In the matched HCV cohort, the risk of CKD was significantly lower in the treated cohort (7-year cumulative incidence, 2.6%; 95% confidence interval [CI], 0.7%–6.9%) than in the untreated cohort (4%; 95% CI, 3.5%–5.2%) (P < 0.001), with an adjusted HR of 0.42 (95% CI, 0.20–0.92; P = 0.03). The results also held in the overall HCV cohort. The number needed to treat for 1 fewer CKD at 7 years was 58. The reduced risk of CKD was greatest (0.35; 0.14–0.87; P = 0.024) in HCV-infected patients who received 6 months or more of IBT. Multivariable stratified analysis verified that greater risk reduction of CKD was present in HCV-infected patients with hyperlipidemia, diabetes, hypertension, and those without coronary heart disease.In conclusion, IBT, especially for 6 or more months, is associated with reduced risk of CKD in HCV-infected patients. Hyperlipidemia, diabetes, hypertension, and coronary heart disease can modify this association.     

Cross-sectional study of the association of 5 single nucleotide polymorphisms with enalapril treatment response among South African adults with hypertension

This study investigates the association of 5 single nucleotide polymorphisms (SNPs) in selected genes (ABO, VEGFA, BDKRB2, NOS3, and ADRB2) with blood pressure (BP) response to enalapril. The study further assessed genetic interactions that exist within these genes and their implications in enalapril treatment response among South African adults with hypertension.A total of 284 participants belonging to the Nguni tribe of South Africa on continuous treatment for hypertension were recruited. Five SNPs in enalapril pharmacogenes were selected and genotyped using MassArray. Uncontrolled hypertension was defined as BP ≥140/90 mm Hg. The association between genotypes, alleles, and BP response to treatment was determined by fitting multivariate logistic regression model analysis, and genetic interactions between SNPs were assessed by multifactor dimensionality reduction.Majority of the study participants were female (75.00%), Xhosa (78.87%), and had uncontrolled hypertension (69.37%). All 5 SNPs were exclusively detected among Swati and Zulu participants. In the multivariate (adjusted) logistic model analysis, ADRB2 rs1042714 GC (adjusted odds ratio [AOR] = 2.31; 95% confidence interval [CI] 1.02–5.23; P = .044) and BDKRB2 rs1799722 CT (AOR = 2.74; 95% CI 1.19–6.28; P = .017) were independently associated with controlled hypertension in response to enalapril. While the C allele of VEGFA rs699947 (AOR = 0.37; 95% CI 0.15–0.94; P = .037) was significantly associated with uncontrolled hypertension. A significant interaction between rs699947, rs495828, and rs2070744 (cross-validation consistency = 10/10; P = .0005) in response to enalapril was observed.We confirmed the association of rs1042714 (ADRB2) and rs1799722 (BDKRB2) with controlled hypertension and established an interaction between rs699947 (VEGFA), rs495828 (ABO), and rs2070744 (NOS3) with BP response to enalapril. Our findings have provided substantial evidence for the use of SNPs as predictors for enalapril response among South Africans adults with hypertension.     

Metabolic syndrome in Zambian adults with human immunodeficiency virus on antiretroviral therapy: Prevalence and associated factors

Metabolic syndrome (MetS) is a constellation of factors including hypertension, abdominal obesity, dyslipidemia, and insulin resistance that separately and together significantly increase risk for cardiovascular disease (CVD) and diabetes. In sub-Saharan Africa, with a substantial burden of human immunodeficiency virus (HIV) and increasing prevalence of CVD and diabetes, there is a paucity of epidemiological data on demographic, laboratory, and clinical characteristics associated with MetS among people with HIV (people with human [PWH]). Therefore, this study aimed to determine the burden and factors influencing MetS in antiretroviral therapy (ART)-experienced individuals in Zambia.We collected cross-sectional demographic, lifestyle, anthropometric, clinical, and laboratory data in a cohort of ART-experienced (on ART for ≥6 months) adults in 24 urban HIV treatment clinics of Zambia between August, 2016 and May, 2020. MetS was defined as having ≥3 of the following characteristics: low high density lipoprotein cholesterol (HDL-c) (<1.0 mmol/L for men, <1.3 for women), elevated waist circumference (≥94 cm for men, ≥80 cm for women), elevated triglycerides (≥1.7 mmol/L), elevated fasting blood glucose (≥5.6 mmol/L), and elevated blood pressure (BP) (systolic BP ≥130 or diastolic BP ≥85 mm Hg). Virological failure (VF) was defined as HIV viral load ≥1000 copies/mL. The following statistical methods were used: Chi-square test, Wilcoxon rank-sum test, and multivariable logistic regression.Among 1108 participants, the median age (interquartile range [IQR]) was 41 years (34, 49); 666 (60.1%) were females. The prevalence of MetS was 26.3% (95% confidence interval [CI] 23.9–29.1). Age (adjusted odds ratio [OR] 1.07; 95% CI 1.04–1.11), female sex (OR 3.02; 95% CI 1.55–5.91), VF (OR 1.98; 95% CI 1.01–3.87), dolutegravir (DTG)-based regimen (OR 2.10; 95% CI 1.05–4.20), hip-circumference (OR 1.03; 95% CI 1.01–1.05), T-lymphocyte count (OR 2.23; 95% CI 1.44–3.43), high-sensitivity C-reactive protein (hsCRP) (OR 1.14; 95% CI 1.01–1.29), and fasting insulin (OR 1.02; 95% CI 1.01–1.04) were significantly associated with MetS.Metabolic syndrome was highly prevalent among HIV+ adults receiving ART in Zambia and associated with demographic, clinical, anthropometric, and inflammatory characteristics. The association between MetS and dolutegravir requires further investigation, as does elucidation of the impact of MetS on ART outcomes in sub-Saharan African PWH.     

24-h-Ambulatory Blood Pressure Monitoring in Sub-Saharan Africa: Hypertension Phenotypes and Dipping Patterns in Malawian HIV+ Patients on Antiretroviral Therapy

Background:Cardiovascular disease and especially hypertension are a growing problem among people living with HIV (PLHIV) on antiretroviral therapy (ART) in sub-Saharan Africa.Objectives:As robust data on hypertension phenotypes associated with distinct cardiovascular risks among PLHIV are limited, we aimed to assess the frequency of white-coat (WCH), masked (MH) hypertension, and blood pressure dipping-patterns in a group of Malawian PLHIV.Methods:As part of the prospective Lighthouse-Tenofovir-Cohort-Study, we analyzed clinical, laboratory and 24-h-ambulatory blood pressure monitoring (ABPM) data of PLHIV from urban Lilongwe with treated or untreated hypertension or raised office blood pressure (OBP) during routine study-visits.Results:118 PLHIV were included and data of 117 participants could be analyzed. Twenty–four-hour ABPM normotension was found in a total of 73 PLHIV including 14/37 on antihypertensive treatment (37.8%). Using strict definitions, i.e. normal OBP plus normal mean BP for all periods of ABPM, controlled hypertension was found in only 4/37 (10.8%) PLHIV on antihypertensive treatment while true normotension was observed in 10/24 untreated patients (41.7%) with previously diagnosed hypertension and 22/56 patients (39.3%) without a medical history of hypertension. WCH with normal BP during all periods of 24-h-ABPM was identified in 12/64 OBP-hypertensive PLHIV (18.8%), primarily in patients with grade 1 hypertension (11/41 patients; 26.8%). MH was found in 17/53 PLHIV with OBP-normotension (32.1%), predominantly in patients with high normal BP (11/20 patients; 55%). The estimated glomerular filtration rate tended to be lower in MH compared to strictly defined normotensive PLHIV (92.0±20.4 vs. 104.8±15.7 ml/min/m²). 64.1 percent of PLHIV (59.5% with 24-h hypertension and 66.7% with 24-h normotension) had abnormal systolic dipping.Conclusion:The high prevalence of WCH and MH with signs of early renal end-organ damage and an abnormal dipping in approximately 2/3 of PLHIV warrants further investigation as these factors may contribute to the increased cardiovascular risk in PLHIV in resource-limited settings like Malawi.Clinical Trial Registration:https://clinicaltrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT02381275","term_id":"NCT02381275"}}NCT02381275), registered March 6th, 2015.     

Prevalence and risk factors for obesity among elderly patients living with HIV/AIDS in a low-resource setting

Obesity is associated with detrimental changes in cardiovascular and metabolic parameters, including blood pressure, dyslipidemia, markers of systemic inflammation, and insulin resistance. In the elderly living with the human immunodeficiency virus (EPLHIV), and being treated with antiretroviral medications, the obesity complications escalate and expose the elderly to the risk of noncommunicable diseases. Given that over 3 million EPLHIV in sub-Sahara Africa, we assessed the prevalence of obesity and its associated factors among EPLHIV in a low-resource setting.This was a cross sectional study of EPLHIV aged 50 years and older, being treated with antiretroviral medications from 2004 to 2018. HIV treatment data collected from multiple treatment sites were analyzed. Baseline characteristics of the participants were described, and multivariable relative risk model was applied to assess the associations between obesity (body mass index [BMI] ≥30 kg/m²) and the prespecified potential risk factors.Of the 134,652 in HIV cohort, 19,566 (14.5%) were EPLHIV: 12,967 (66.3%) were normal weight (18.5 ≤ BMI < 25), 4548 (23.2%) were overweight (25 ≤ BMI < 30), while 2,051 (10.5%) were obese (BMI ≥30). The average age the normal weight (57.1; standard deviation 6.6) and the obese (56.5; standard deviation 5.5) was similar. We observed that being an employed (relative risk [RR] 1.71; 95% confidence interval [CI] 1.48–2.00; P < .001), educated (RR 1.93; 95% CI 1.54–2.41; P < .001), and presence of hypertension (RR 1.78; 95% CI 1.44–2.20; P < .001), increased the risk of obesity. Also, being male (RR 0.38; 95% CI 0.33–0.44; P < .001), stages III/IV of the World Health Organization clinical stages of HIV (RR 0.58; 95% CI 0.50–0.68; P < .001), tenofovir-based regimen (RR 0.84; 95% CI 0.73–0.96, P < .001), and low CD₄ count (RR 0.56; 95% CI 0.44–0.71; P < .001) were inversely associated with obesity.This study demonstrates that multiple factors are driving obesity prevalence in EPLHIV. The study provides vital information for policy-makers and HIV program implementers in implementing targeted-interventions to address obesity in EPLHIV. Its findings would assist in the implementation of a one-stop-shop model for the management of HIV and other comorbid medical conditions in EPLHIV.     

Association Between Diabetic Macular Edema and Cardiovascular Events in Type 2 Diabetes Patients: A Multicenter Observational Study

Diabetic macular edema (DME) is the main cause of visual loss associated with diabetes but any association between DME and cardiovascular events is unclear.This study aims to describe the possible association between DME and cardiovascular events in a multicenter cross-sectional study of patients with type 2 diabetes.Two thousand eight hundred seven patients with type 2 diabetes were recruited from diabetes and nephrology clinical institutional centers participating in the DIAB 2 NEPHROGENE study focusing on diabetic complications. DME (presence/absence) and diabetic retinopathy (DR) classification were based on ophthalmological report and/or on 30° color retinal photographs. DR was defined as absent, nonproliferative (background, moderate, or severe) or proliferative. Cardiovascular events were stroke, myocardial infarction, and lower limb amputation.Details regarding associations between DME and cardiovascular events were evaluated.The study included 2807 patients with type 2 diabetes, of whom 355 (12.6%) had DME. DME was significantly and independently associated with patient age, known duration of diabetes, HbA1c, systolic blood pressure, and DR stage. Only the prior history of lower limb amputation was strongly associated with DME in univariate and multivariate analyses, whereas no association was found with regard to myocardial infarction or stroke. Moreover, both major (n = 32) and minor lower limb (n = 96) amputations were similarly associated with DME, with respective odds ratio of 3.7 (95% confidence interval [CI], 1.77–7.74; P = 0.0012) and of 4.29 (95% CI, 2.79–6.61; P < 0.001).DME is strongly and independently associated with lower limb amputation in type 2 diabetic patients.     

Cross-sectional study of diabetes kidney disease in the Eastern Cape,South Africa

Diabetes mellitus (DM) is an independent risk factor for the development of kidney disease. This study assesses the prevalence and determinants of asymptomatic kidney disease in individuals with DM attending health facilities in OR Tambo district, Eastern Cape, South Africa.In this cross-sectional analysis, medical data of 327 individuals receiving care for DM in primary health care centers in OR Tambo district, Eastern Cape between June and November 2013 were reviewed. Significant kidney disease was defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m² in accordance with the guidelines of the Society of Endocrinology, Metabolism and Diabetes of South Africa (2017).One-quarter of the 327 participants (n = 80) had significant kidney disease. Female sex [odds ratio (OR) = 5.2; 95% confidence interval (95% CI) 1.2–23.5], never used alcohol (OR = 13.4; 95% CI 2.5–72.1), hypertension (OR = 16.2; 95% CI 2.0–130.0), triglyceride (TG)/high-density lipoprotein (HDL) ratio (OR = 1.2; 95% CI 1.0–1.5), current smoker (OR = 1127.9; 95% CI 162.9–7808.9), former smoker (OR = 13.3; 95% CI 4.1–41.4), and longer duration of diabetes (OR = 4.6; 95% CI 1.6–13.0) were the independent determinants of significant kidney disease among the participants. A significant dose--effect relationship exists between renal disease and smoking status (P < .0001), duration of DM (P < .001), glycemic status (P = .025), and body mass index (P = .003).There is a high rate of undiagnosed kidney disease in this setting, which was independently associated with female sex and presence of other cardiovascular risk factors. Strategic interventions targeting screening and monitoring of renal functions in individuals with DM are urgently needed in this region.