HIV-related Factors Research Articles

Cytomegalovirus-specific CD8+ T-cell responses are associated with arterial blood pressure in people living with HIV.

People living with HIV (PLHIV) are at increased risk for cardiovascular disease (CVD), and immunity against cytomegalovirus (CMV) may be a contributing factor. We hypothesized that enhanced T-cell responses against CMV and CMV-IgG antibody-levels are associated with higher arterial blood pressure in PLHIV. We assessed serum CMV-IgG, systolic- (SBP) and diastolic- (DBP) blood pressure, pulse pressure (PP), traditional risk factors, activated CD8+ T-cells (CD38+HLA-DR+), senescent CD8+ T-cells (CD28-CD57+) and interleukin-6 (IL-6) in 60 PLHIV and 31 HIV-uninfected controls matched on age, gender, education and comorbidity. In PLHIV, expression of interleukin-2, tumor necrosis factor-α and interferon-γ was measured by intracellular-cytokine-staining after stimulation of T-cells with CMV-pp65 and CMV-gB. Associations between CMV-specific immune responses and hypertension, SBP, DBP or PP were assessed by multivariate logistic and linear regression models adjusted for appropriate confounders. The median age of PLHIV was 47 years and 90% were male. Prevalence of hypertension in PLHIV was 37% compared to 55% of HIV-uninfected controls. CMV-specific CD8+ T-cell responses were independently associated with higher PP (CMV-pp65; β = 2.29, p = 0.001, CMV-gB; β = 2.42, p = 0.001) in PLHIV. No significant differences were found with regard to individual measures of SBP and DBP. A possible weak association was found between CMV-IgG and hypertension (β = 1.33, p = 0.049) after adjustment for age, smoking and LDL-cholesterol. HIV-related factors, IL-6, CD8+ T-cell activation or CD8+ T-cell senescence did not mediate the associations, and no associations were found between CMV-specific CD4+ T-cell responses and blood pressure in PLHIV. In conclusion, increased arterial blood pressure in PLHIV may be affected by heightened CMV-specific CD8+ T-cell responses.

Metabolic Syndrome and Associated Factors Among HIV-infected Patients at Bafoussam Regional Hospital, Cameroon

The use of highly active antiretroviral therapy (HAART) transformed HIV infection to a chronic disease, and the complexity of the physiological disorders generated leads to the disruption of body fat distribution and insulin resistance. The resulting metabolic syndrome has rarely been investigated among people living with HIV/AIDS in Cameroon. The aim of the current work was to determine the prevalence of metabolic syndrome and associated factors among people living with HIV/AIDS under HAART at the Bafoussam Regional Hospital in Cameroon. A retrospective, cross-sectional study was conducted to collect demographic, clinical and therapeutic data from 371 people living with HIV/AIDS and who are under HAART at the Bafoussam Regional Hospital from November 2017 to February 2019. Abbott Real-time HIV-1 system, FACSCOUNT cytometer and FULLYSMART automates were used to determine HIV RNA level, CD4 cell count and biochemical parameters respectively. The metabolic syndrome was defined according to the International Diabetes Federation (IDF) and the National Cholesterol Education Program -Adult Treatment Panel III (NCEP-ATPIII) criteria. The overall prevalence of metabolic syndrome was 37.74% by IDF and 28.84% by ATPIII. Among patients with metabolic syndrome, HDL-hypocholesterolemia was the most prevalent feature (92.14%). We found that aging (OR, 1.05; p, 0.005), HIV RNA level (OR, 3.42; p, 0.001), family history of metabolic and coronary heart disease (OR, 2.24; P, 0.04), alcohol consumption (OR, 4; P, 0.004) and nutritional supplements (OR, 3.5; P<0.001) were the independent predictors of metabolic syndrome. Male sex (OR, 0.22; p,<0.001), use of traditional medicines (OR, 0.28; P<0.001), Cotrimoxazole prophylaxis (OR, 0.45; p, 0.007) and Lamivudine-Tenofovir-Efavirenz antiretroviral regimen (OR, 0.26; p<0.001) were protective factors. The prevalence of metabolic syndrome is on the increase among people living with HIV/AIDS in our study population. Both HIV related factors and traditional risk factors were associated with metabolic syndrome.

Incidence of chronic obstructive pulmonary disease in people with HIV in Ontario, 1996-2015: a retrospective population-based cohort study.

Because of high smoking rates and HIV-related factors, people with HIV may be at high risk for chronic obstructive pulmonary disease (COPD); however, population-based estimates of the incidence of COPD among people with HIV are lacking, particularly for women. We compared the incidence of COPD among Ontario adults aged 35 years or more with and without HIV between Jan. 1, 1996, and Dec. 31, 2015. We conducted a population-based study using Ontario's health administrative databases. We compared the incidence of COPD between people with and without HIV using standardized incidence ratios and generalized estimating equations with a log link function. We identified 1849 people with HIV and 1 168 727 HIV-negative people who were newly diagnosed with COPD between 1996 and 2015. People with HIV were younger than HIV-negative people (mean age 49.7 [standard deviation 10.4] yr v. 62.2 [standard deviation 14.8] yr; standardized difference 0.98). Rates of COPD were higher among people with HIV than among HIV-negative people (10.4 v. 9.0 cases per 1000 person-years; standardized incidence ratio 1.16, 95% confidence interval [CI] 1.10 to 1.21; adjusted rate ratio 1.34, 95% CI 1.27 to 1.41). In sex-stratified analyses, rates of COPD were higher among men with HIV (adjusted rate ratio 1.32, 95% CI 1.24 to 1.40) and women with HIV (adjusted rate ratio 1.54, 95% CI 1.37 to 1.72) than among men and women without HIV. In a sensitivity analysis, smoking explained observed differences in COPD incidence. People with HIV had higher rates of incident COPD than HIV-negative people. This may reflect the disproportionately higher prevalence of smoking among the former.

Cardiovascular disease risk in an urban African population: a cross-sectional analysis on the role of HIV and antiretroviral treatment

BackgroundLife expectancy is increasing in the HIV-positive population and age-related non-communicable diseases, such as cardiovascular disease, (CVD) are seen more frequently. This study investigated to what extent HIV and antiretroviral therapy (ART) is associated with CVD risk in an urban African population.MethodsA cross-sectional study was performed in Johannesburg, South Africa, between July 2016 and November 2017. Both HIV-positive adults (ART-naïve, or on first- or second-line ART), as well as age and sex matched HIV-negative controls who were family or friends of the HIV-positive participants were included. Data were collected on demographics, cardiovascular risk factors, HIV-related characteristics, carotid intima-media thickness (CIMT) and carotid distensibility. The association between HIV, ART and CIMT and distensibility was analysed with linear regression models, adjusting for age, gender and CVD risk factors.ResultsThe study included 548 participants, 337 (62%) females, age 38.3 ± 9.5 years of whom 104 (19.0%) were HIV-positive, ART-naïve; 94 (17.2%) were on first-line ART; 197 (35.9%) were on second-line ART; and 153 (27.9%) were HIV-negative. Participants on second-line ART had higher CIMT and lower distensibility compared to the other groups (p < 0.001). After adjustment for age, these outcomes were similar between groups. Further adjustment for CVD and HIV-related factors did not alter the findings.ConclusionNeither HIV nor ART was associated with CIMT or carotid distensibility in this urban African population. Longitudinal studies are needed to fully understand the relationship between HIV and CVD across different populations.

MicroRNA biomarkers associated with type 1 myocardial infarction in HIV-positive individuals.

Individuals with HIV suffer a higher burden of cardiovascular diseases. Traditional cardiovascular risk scores consistently underestimate cardiovascular risk in this population. Subsets of microRNAs (miRNAs) are differentially expressed among individuals with cardiovascular disease and individuals infected with HIV. However, no study has clarified whether specific miRNAs may be biomarkers for cardiovascular disease in individuals with HIV. We compared the miRNA expression profiles of 34 HIV-positive individuals who had experienced clinically adjudicated type I myocardial infarctions (MI) with the profiles of 76 HIV-positive controls matched by traditional cardiovascular risk factors and HIV-specific measures. Using the elastic net algorithm, we selected miRNAs most strongly associated with incident MI and then used conditional Cox proportional hazards regression and cross-validation to evaluate miRNAs and their association with incident MI. We evaluated whether miRNA markers would improve risk classification relative to the Framingham Risk Score. Higher miR-125a-5p and miR-139-5p expression levels were each associated with increased risk of developing MI after adjustment for Framingham Risk Score and HIV-related factors (hazard ratio 2.43, P = 0.018; hazard ratio 2.13, P = 0.048, respectively). Compared with the Framingham Risk Score alone, adding expression levels of miR-125a-5p or miR-139-5p resulted in an integrated discrimination improvement of 10.1 or 5.8%, respectively. MiR-125a-5p and miR-139-5p, transcripts known to be differentially expressed in HIV-positive individuals, may serve as unique biomarkers predictive of cardiovascular disease in these patients and may help clarify processes because of HIV infection that contribute to cardiovascular disorders in this population.

HIV-Associated NAFLD: Disease Burden and Management

Highly potent anti-retroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV) has led to dramatic improvements in quality of life and lifespan in persons living with HIV (PLWH). PLWH, however, are suffering from other comorbid conditions, including non-alcoholic fatty liver disease (NAFLD). This review summarizes the epidemiology and pathophysiology of NAFLD in PLWH and explores unique diagnostic and treatment considerations in this population. Though it is well established that there is a high prevalence of NAFLD in PLWH, the mechanisms underlying NAFLD in this population are just beginning to be explored. Traditional NAFLD risk factors, including insulin resistance, visceral adiposity, and genetics, have been consistently linked with NAFLD in PLWH. In addition, HIV-related factors including mitochondrial dysfunction, microbiome alterations, and direct effects of the virus and of ART may play a role. Given the burden of NAFLD in PLWH, further studies are necessary to investigate mechanisms specific to HIV with which to target therapies.

HIV RNA, CD4+ Percentage, and Risk of Hepatocellular Carcinoma by Cirrhosis Status.

Despite increasing incidence of hepatocellular carcinoma (HCC) among HIV-infected patients, it remains unclear if HIV-related factors contribute to development of HCC. We examined if higher or prolonged HIV viremia and lower CD4+ cell percentage were associated with HCC. We conducted a cohort study of HIV-infected individuals who had HIV RNA, CD4+, and CD8+ cell counts and percentages assessed in the Veterans Aging Cohort Study (1999-2015). HCC was ascertained using Veterans Health Administration cancer registries and electronic records. Cox regression was used to determine hazard ratios (HR, 95% confidence interval [CI]) of HCC associated with higher current HIV RNA, longer duration of detectable HIV viremia (≥500 copies/mL), and current CD4+ cell percentage less than 14%, adjusting for traditional HCC risk factors. Analyses were stratified by previously validated diagnoses of cirrhosis prior to start of follow-up. Among 35659 HIV-infected patients, 302 (0.8%) developed HCC over 281441 person-years (incidence rate = 107.3 per 100000 person-years). Among patients without baseline cirrhosis, higher HIV RNA (HR = 1.25, 95% CI = 1.12 to 1.40, per 1.0 log10 copies/mL) and 12 or more months of detectable HIV (HR = 1.47, 95% CI = 1.02 to 2.11) were independently associated with higher risk of HCC. CD4+ percentage less than 14% was not associated with HCC in any model. Hepatitis C coinfection was a statistically significant predictor of HCC regardless of baseline cirrhosis status. Among HIV-infected patients without baseline cirrhosis, higher HIV RNA and longer duration of HIV viremia increased risk of HCC, independent of traditional HCC risk factors. This is the strongest evidence to date that HIV viremia contributes to risk of HCC in this group.

344. HIV and Diabetes in the Era of Antiretroviral Therapy

BackgroundWith advancements in ART, non-AIDS comorbidities are becoming more common among people living with HIV (PWH). In this analysis, we identified PWH followed at a single Ryan White HIV Clinic in Alabama and determined the overall prevalence of diabetes (DM). We then evaluated the cohort for risk factors associated with DM.MethodsThe records of all PWH who attended at least one routine care HIV primary provider visit from 2009 to 2018 at the UAB 1917 HIV Clinic in Birmingham, AL were abstracted. We defined DM as individuals having ≥1 of the following: (1) diagnosis of DM and receiving any diabetic medication, (2) Hgb A1c ≥ 6.5%, (3) any glucose >200 mg/dL. We evaluated the association of traditional, demographic, and HIV-specific risk factors with PWH with and without DM using Chi-square and Wilcoxon rank-sum testing. Univariate significance and amount of missing data were considered when constructing the multivariable logistic regression model to identify independent associations.ResultsOf the 5247 PWH assessed, 1178 were female (23%), 45 transgender persons (1%); 3235 (62%) black, 1834 (35%) white. At baseline, the median age was 37.5 years, median BMI 24.5 kg/m2, median CD4+ count 333 c/mm3. Overall, 1110 PWH developed DM (21%). By univariate analysis, numerous traditional, demographic and HIV-related risk factors were associated with diagnosis of DM (see Table 1). By multivariable analysis, the following factors were independently associated with DM: traditional (antihypertensive use, aspirin use, glucocorticoid use, statin use, comorbid CKD, comorbid liver disease), demographic (black race, female gender, older age), and HIV-related (nadir CD4) (P < 0.05 for all).ConclusionOver 20% of PWH had a diagnosis of DM. Both traditional and HIV-related factors were independently associated with DM. Notably, lower nadir CD4 and longer time to ART initiation were key HIV-related factors. Additionally, a majority of PWH with DM had multimorbidity (85%) and polypharmacy (90%). Despite the lower complexity of modern ART, the care of PWH remains challenging, partly because of cardiometabolic comorbidities, including DM. Effective diabetes prevention and treatment strategies for PWH should be prioritized. Disclosures All authors: No reported disclosures.

346. Factors Associated with Hypertension in Young Adults with Perinatally-Acquired HIV Infection: a Case–Control Study

BackgroundThe incidence of systemic hypertension (HTN) among perinatally-HIV-infected (PHIV) patients appears to increase as they enter adulthood. Among non-perinatally HIV-infected adults both traditional and HIV-associated risk factors have been found to contribute to HTN. Whether these same factors contribute to HTN in PHIV is unknown. The purpose of this study was to determine the socio-demographic, clinical, virologic, and immunologic factors associated with HTN among a cohort of PHIV adolescents and young adults, aged ≥18 years.MethodsWe conducted a case–control study among a population of 160 PHIV adults with and without HTN who were receiving care at the University of Maryland and aged 18–35 years as of December 31, 2017. Covariates assessed included traditional risk factors such as age, family history of HTN, and smoking, as well as HIV- and antiretroviral-associated covariates.ResultsWe identified 49 HTN cases (30.6%) and 111 (69.4%) controls. There were no significant differences in the odds of most traditional (age, gender, race, family history of HTN, tobacco, alcohol, and/or other drug use) or HIV-associated (CD4 nadir <100 cells/mm3, individual ART exposure, ART interruption) risk factors among PHIV adults with HTN compared with those with no diagnosis of HTN. Cases had lower odds of a history of treatment with lopinavir/ritonavir (LPV/r). Cases had 3.7 (95% CI 1.11, 12.56) times the odds of a prior diagnosis of chronic kidney disease (CKD) compared with controls after controlling for CD4 nadir and ARV treatment history.ConclusionThe results of this study suggest that most traditional and HIV-related risk factors do not appear to increase the odds of having HTN in this PHIV cohort. However, HTN among PHIV may be driven in part by CKD, and a focus on the prevention and early management of CKD in this group may be necessary to prevent the development of HTN. Additionally, there may be as yet unidentified risk factors for HTN among PHIV which require further exploration. Given the large and growing population of PHIV entering adulthood worldwide, it is imperative to explore risk factors for and effects of HTN in large, diverse PHIV populations.Disclosures All authors: No reported disclosures.

Isoniazid Preventive Therapy and Pregnancy Outcomes in Women Living With Human Immunodeficiency Virus in the Tshepiso Cohort.

BackgroundBoth pregnancy and human immunodeficiency virus (HIV) increase the risk of tuberculosis disease, which results in poor maternal, pregnancy, and infant outcomes. Isoniazid preventive therapy (IPT) reduces mortality among individuals living with HIV in high-burden settings but has recently been associated with adverse pregnancy outcomes when initiated during pregnancy.MethodsIn this secondary analysis, we used multivariable logistic regression to evaluate the association between IPT exposure and adverse pregnancy outcomes (fetal demise, prematurity, low birth weight, congenital anomaly) in pregnant women living with HIV enrolled as controls in the Tshepiso study, a prospective observational cohort of pregnant women living with HIV with and without tuberculosis disease in Soweto, South Africa, from 2011–2014.ResultsThere were 151 women enrolled with known pregnancy outcomes; 69 (46%) reported IPT initiation during pregnancy. Of the 69 IPT-exposed women, 11 (16%) had an adverse pregnancy outcome compared with 23 (28%) IPT-unexposed women. The adjusted odds of having an adverse pregnancy outcome was 2.5 (95% confidence interval, 1.0–6.5; P = .048) times higher in IPT-unexposed women compared with IPT-exposed women after controlling for maternal age, CD4 count, viral load, antiretroviral regimen, body mass index, and anemia.ConclusionsIPT exposure during pregnancy was not negatively associated with pregnancy outcomes after controlling for demographic, clinical, and HIV-related factors. These results provide some reassurance that IPT can be safely used in the second or third trimester of pregnancy. Additional research is needed to evaluate the safety of IPT and new short-course tuberculosis preventive therapies during pregnancy.

Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials.

BackgroundInitiation of antiretroviral therapy (ART) often leads to weight gain. While some of this weight gain may be an appropriate return-to-health effect, excessive increases in weight may lead to obesity. We sought to explore factors associated with weight gain in several randomized comparative clinical trials of ART initiation.MethodsWe performed a pooled analysis of weight gain in 8 randomized controlled clinical trials of treatment-naive people living with human immunodeficiency virus (HIV) initiating ART between 2003 and 2015, comprising >5000 participants and 10 000 person-years of follow-up. We used multivariate modeling to explore relationships between demographic factors, HIV disease characteristics, and ART components and weight change following ART initiation.ResultsWeight gain was greater in more recent trials and with the use of newer ART regimens. Pooled analysis revealed baseline demographic factors associated with weight gain including lower CD4 cell count, higher HIV type 1 RNA, no injection drug use, female sex, and black race. Integrase strand transfer inhibitor use was associated with more weight gain than were protease inhibitors or nonnucleoside reverse transcriptase inhibitors (NNRTIs), with dolutegravir and bictegravir associated with more weight gain than elvitegravir/cobicistat. Among the NNRTIs, rilpivirine was associated with more weight gain than efavirenz. Among nucleoside/nucleotide reverse transcriptase inhibitors, tenofovir alafenamide was associated with more weight gain than tenofovir disoproxil fumarate, abacavir, or zidovudine.ConclusionsWeight gain is ubiquitous in clinical trials of ART initiation and is multifactorial in nature, with demographic factors, HIV-related factors, and the composition of ART regimens as contributors. The mechanisms by which certain ART agents differentially contribute to weight gain are unknown.

SUBCLINICAL CORONARY ATHEROSCLEROSIS AMONG INDIVIDUALS WITH HIV ON ANTIRETROVIRAL THERAPY - PRELIMINARY RESULTS FROM THE CANADIAN HIV AND AGING COHORT STUDY (CHACS)

The Canadian HIV and Aging Cohort Study (CHACS) is a large, controlled, prospective cohort recruiting participants living with HIV, and participants unexposed to HIV. The CHACS focus on identifying the prevalence, type and determinants of premature cardiovascular disease in HIV+ individuals. The objective of the present cardiovascular imaging substudy nested in the CHACS is to compare subclinical coronary plaque burden and characteristics between HIV+ and HIV- individuals and to evaluate the association of coronary plaque with HIV-related factors. This cross-sectional study was approved by our ethics committee. Participants provided written consent. Consecutive HIV+ and HIV- participants were prospectively recruited for cardiac computed tomography (CT). Eligibility criteria were absence of known coronary artery disease and low/intermediate 10-yr Framingham risk score (FRS, 5-20%). CT was used for calcium scoring and plaque assessment. Assessors were blinded to HIV status. Multivariate regression models were used. A total of 265 participants (181 HIV+ (92% males), 84 HIV- (77 % males)) were included (mean 56 yo), with similar FRS. Smoking (p < 0.001) and dyslipidemias (p ≤ 0.02) were increased in HIV+ participants. All HIV+ participants were on antiretroviral therapy. After adjusting for cardiovascular risk factors, burden of calcium and overall plaque was similar between HIV+ and HIV- participants. However, HIV+ participants had an increased volume (25 and 5 mm3/participant, p=0.03) of noncalcified plaques compared to HIV- participants. Prevalence and volume of calcified (p= 0.12 and 0.29) and mixed (p= 0.18 and 0.17) plaques, as well as ≥ 70% stenosis (p=0.99) were similar between HIV+ and HIV- participants. In HIV participants, total plaque volume, noncalcified plaque volume and mixed plaque volume (p=0.01, 0.03 and 0.006) increased with the use of protease inhibitors; noncalcified plaque volume (p=0.02) increased with the use of nucleoside reverse transcriptase inhibitors. To our knowledge, this is the largest Canadian imaging study of HIV-associated coronary atherosclerosis. In line with previous studies, our results confirm that asymptomatic HIV+ individuals under antiretroviral therapy have increased noncalcified plaque in comparison to HIV- individuals, after adjustment for cardiovascular risk factors. Noncalcified plaques are usually considered vulnerable and this finding could suggest one anatomic substrate for the known increased risk of myocardial infarction in the HIV population. Additionally, our data are intended as a basis for novel correlative analyses (e.g. carotid wall biomechanics, advanced immunological factors, frailty) planned with other teams of the CHACS.

The HIV-Related Risk Factors of the Cisgender Male Sexual Partners of Transgender Women (MSTW) in the United States: A Systematic Review of the Literature.

Cisgender male sexual partners of transgender women (MSTW) may be at risk for HIV infection. We performed a review of HIV risk factors among MSTW. We searched PubMed database for empirical quantitative U.S.-based studies that included MSTW and were published in English up to November 2018. Of the 4,680 total papers identified, 6 unique studies were included. MSTW displayed heterogeneity in HIV risk factors (e.g., condom use, sexual partners, sexual positions, substance use). In our exploratory meta-analyses, estimated prevalence of self-reported HIV positive status among MSTW was 30.6%, HIV unknown status was 8.8%, and self-reported condomless anal sex with transgender women was 46.1%. Reports of sexual health communication with transgender women was low. More research on MSTW populations is needed to better understand this population's unique needs in the context of recent advancements in HIV prevention.

P5338Atherosclerotic cardiovascular events in people living with Human Immunodeficiency Virus

Abstract Background People living with Human Immunodeficiency Virus (PLWHIV) under antiretrovirals have an increased risk of atherosclerotic cardiovascular disease (ASCVD) events. The risk factors associated with ASCVD events in this high risk population are various including traditional vascular risk factors and specific HIV-related factors. However their respective influence is questionable. Purpose Our aim was to determine the incidence of ASCVD events in a large cohort of PLWHIV and to identify the risk factors associated. Methods We conducted a longitudinal observational cohort study of asymptomatic PLWHIV at high risk of ASCVD addressed to our preventive cardiovascular unit for non-invasive cardiovascular evaluation. The first ASCVD event was censored and included CV death, acute coronary syndromes, coronary and peripheral revascularizations (PCI or CABG or endarterectomy or limb procedures) and ischemic strokes. Results From January 2003 to December 2014, 763 consecutive asymptomatic PLWHIV were enrolled (mean age of 51.3±8.3 years, 87% men, 90% were free of known coronary artery disease, mean Left ventricular ejection fraction 60%). At baseline, traditional CV risk factors were as follow: 54% had dyslipidemia, 43% hypertension, 35% were active smokers, 22% had family history of CAD and 11% were diabetics. Statins were prescribed in 38% of the cohort, aspirin in 14%, clopidogrel in 14% betablockers in 14%, RAS blockers in 32%, Calcium channel blockers in 8%. At baseline, median duration of HIV seropositivity was 19.8 years (14.0–23.6), 94% were under ARV predominantly protease inhibitors (68%). Median CD4 cell count was 545/mm3 (404–745) and 92% had undetectable HIV viral load. During a median follow up of 5.8 years (3.7–8.7), 58 (7.3%) subjects had a first ASCVD event (incidence of 12.70 [9.78–16.51] per 1000 persons-years) including 5 cardiovascular deaths, 14 ACS, 20 coronary revascularizations, 13 peripheral vascular procedures and 6 strokes) with a median time of occurrence of 3.1 years (1.5–5.1). CV death (first and second ASCVD events) occurred in 8 patients (22%) after CV death related to malignancies (33%) but before deaths related to unexplained causes (21%), infectious disease (13%), liver disease (8%) and suicides (3%). Coronary events including coronary death, MI, and coronary revascularization occurred in 39 patients (5.2%); Incidence of 8.28 [6.00–11.43] per 1000 persons-years. Conventional multivariate Cox model shows that age and tobacco were the independent risk factors associated with ACSVD events [Hazard ratio (HR) 1.04, 95% CI 0.99–1.09, p=0.05 and HR 2.17, 95% CI 1.07–4.38, p=0.03]. Conclusion Traditional vascular risk factors (age and active smoking) are associated with the occurrence of ASCVD events predominantly coronary artery disease in our observational cohort of asymptomatic PLWIHV at high risk for ASCVD. Cardiovascular prevention including tobacco cease action is mandatory in the aging HIV population.

Associations of Urine Biomarkers with Kidney Function Decline in HIV-Infected and Uninfected Men

Background: HIV-infected (HIV+) persons are at increased risk of chronic kidney disease, but serum creatinine does not detect early losses in kidney function. We hypothesized that urine biomarkers of kidney damage would be associated with subsequent changes in kidney function in a contemporary cohort of HIV+ and HIV-uninfected (HIV–) men. Methods: In the Multicenter AIDS Cohort Study, we measured baseline urine concentrations of 5 biomarkers from 2009 to 2011 in 860 HIV+ and 337 HIV– men: albumin, alpha-1-microglobulin (α1m), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and procollagen type III N-terminal propeptide (PIIINP). We evaluated associations of urine biomarker concentrations with annual changes in estimated glomerular filtration rate (eGFR) using multivariable linear mixed models adjusted for demographics, traditional kidney disease risk factors, HIV-related risk factors, and baseline eGFR. Results: Over a median follow-up of 4.8 years, the average annual eGFR decline was 1.42 mL/min/1.73 m²/year in HIV+ men and 1.22 mL/min/1.73 m²/year in HIV– men. Among HIV+ men, the highest vs. lowest tertiles of albumin (–1.78 mL/min/1.73 m²/year, 95% CI –3.47 to –0.09) and α1m (–2.43 mL/min/1.73 m²/year, 95% CI –4.14 to –0.73) were each associated with faster annual eGFR declines after multivariable adjustment. Among HIV– men, the highest vs. lowest tertile of α1m (–2.49 mL/min/1.73 m²/year, 95% CI –4.48 to –0.50) was independently associated with faster annual eGFR decline. Urine IL-18, KIM-1, and PIIINP showed no independent associations with eGFR decline, regardless of HIV serostatus. Conclusions: Among HIV+ men, higher urine albumin and α1m are associated with subsequent declines in kidney function, independent of eGFR.

A Person-Centered Approach to HIV-Related Protective and Risk Factors for Young Black Men Who Have Sex with Men: Implications for Pre-exposure Prophylaxis and HIV Treatment as Prevention.

Although young Black men who have sex with men (YBMSM) are disproportionately affected by HIV, they may be more heterogeneous as a group than is typically appreciated. Thus, the present study used a person-centered data-analytic approach to determine profiles of HIV-related risk among YBMSM and whether these profiles could be distinguished by age, HIV status, and socioeconomic risk (i.e., socioeconomic distress). YBMSM (N = 1808) aged 18 to 29years completed a survey of sociodemographic characteristics, HIV status, and HIV-related behavioral and attitudinal factors (i.e., safer-sex self-efficacy, negative condom attitudes, being in difficult sexual situations, being in difficult sexual relationships, HIV treatment optimism, perceived HIV stigma). Latent profile analysis was used to identify HIV risk profiles and whether age, HIV status, and socioeconomic distress were associated with these profiles. Four profiles emerged: low-, medium-, and high-risk profiles, respectively, and a mixed profile characterized by a tendency to be in difficult sexual situations and relationships while also reporting high safer-sex self-efficacy and low negative attitudes toward condom use. Difficult sexual situations emerged as the key defining indicator of whether a profile reflected higher or lower risk. Younger age, being HIV-positive, and socioeconomic distress were associated with having a higher-risk profile. Given that unique risk profiles emerged that were differentially predicted by sociodemographic characteristics and HIV status, these findings have implications for tailoring interventions to the needs of different subgroups of YBMSM. Also, disempowering or risky sexual situations and relationships among YBMSM must be addressed.

Predictors of Ischemic and Hemorrhagic Strokes Among People Living With HIV: The D:A:D International Prospective Multicohort Study

BackgroundHypertension is a stronger predictor of hemorrhagic than ischemic strokes in the general population. We aimed to identify whether hypertension or other risk factors, including HIV-related factors, differ in their associations with stroke subtypes in people living with HIV (PLWHIV). MethodsHIV-1-positive individuals from the Data collection on Adverse events of anti-HIV Drugs (D:A:D) study were followed from the time of first blood pressure (BP) measurement after 1/1/1999 or study entry until the first of a validated stroke, 6 months after last follow-up or 1/2/2014. Stroke events were centrally validated using standardized criteria. Hypertension was defined as one systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg. Poisson and Cox proportional hazards regression models determined associations of established cerebro/cardiovascular disease and HIV-related risk factors with stroke and tested whether these differed by stroke subtype. Findings590 strokes (83 hemorrhagic, 296 ischemic, 211 unknown) occurred over 339,979 person-years (PYRS) (incidence rate/1000 PYRS 1.74 [95% confidence interval (CI) 1.60–1.88]). Common predictors of both hemorrhagic and ischemic strokes were hypertension (relative hazard 3.55 [95% CI 2.29–5.50] and 2.24 [1.77–2.84] respectively) and older age (1.28 [1.17–1.39] and 1.19 [1.12–1.25]). Male gender (1.62 [1.14–2.31] and 0.60 [0.35–0.91]), previous cardiovascular events (4.03 [2.91–5.57] and 1.44 [0.66–3.16]) and smoking (1.90 [1.41–2.56] and 1.08 [0.68–1.71]) were stronger predictors of ischemic then hemorrhagic strokes, whereas hypertension, hepatitis C (1.32 [0.72–2.40] and 0.46 [0.30–0.70]) and estimated glomerular filtration rate <60 mL/min/1.72 m3 (4.80 [2.47–9.36] and 1.04 [0.67–1.60]) were stronger predictors of hemorrhagic than ischemic strokes. A CD4 count <200 cells/μL was associated with an increased risk of hemorrhagic stroke only. InterpretationRisk factors for stroke may differ by subtype in PLWHIV, emphasizing the importance of further research to increase the precision of stroke risk estimation.

Prevalence of impaired renal function in virologically suppressed people living with HIV compared with controls: the Copenhagen Comorbidity in HIV Infection (COCOMO) study*

While renal impairment is reported more frequently in people living with HIV (PLWH) than in the general population, the PLWH samples in previous studies have generally been dominated by those at high renal risk. Caucasian PLWH who were virologically suppressed on antiretroviral treatment and did not have injecting drug use or hepatitis C were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) study. Sex- and age-matched controls were recruited 1:4 from the Copenhagen General Population Study up to November 2016. We defined renal impairment as one measurement of estimated glomerular filtration rate≤60mL/min/1.73m2 , and assessed associated factors using adjusted logistic regression models. The impact of HIV-related factors was explored in a subanalysis. Among 598 PLWH and 2598 controls, the prevalence of renal impairment was 3.7% [95% confidence interval (CI) 2.3-5.5%] and 1.7% (95% CI 1.2-2.2%; P=0.0014), respectively. After adjustment, HIV status was independently associated with renal impairment [odds ratio (OR) 3.4; 95% CI 1.8-6.3]. In addition, older age [OR 5.4 (95% CI 3.9-7.5) per 10years], female sex [OR 5.0 (95% CI 2.6-9.8)] and diabetes [OR 2.9 (95% CI 1.3-6.7)] were strongly associated with renal impairment. The association between HIV status and renal impairment became stronger with older age (P=0.02 for interaction). Current and nadir CD4 counts, duration of HIV infection and previous AIDS-defining diagnosis were not associated with renal impairment among virologically suppressed PLWH. The prevalence of renal impairment is low among low-risk virologically suppressed Caucasian PLWH, but remains significantly higher than in controls. Renal impairment therefore remains a concern in all PLWH and requires ongoing attention.

Agreement and Discrepancy on Emotional and Behavioral Problems Between Caregivers and HIV-Infected Children and Adolescents From Uganda.

Background: HIV-infected children and adolescents (CA-HIV) face significant mental health challenges related to a broad range of biological and psychosocial factors. Data are scarce on the agreement and discrepancy between caregivers and CA-HIV regarding emotional and behavioral problems (EBPs) in CA-HIV. Objectives: We determined agreement between self- versus caregiver- reported EBPs and describe factors associated with informant discrepancy among caregiver–youth dyads who participated in the “Mental health among HIV-infected CHildren and Adolescents in KAmpala and Masaka, Uganda” (CHAKA) study. Methods: In a cross-sectional sample, caregiver-reported EBPs were assessed with the Child and Adolescent Symptom Inventory-5 (CASI-5), and self-reported problems were evaluated with the Youth Inventory-4 (YI-4) in 469 adolescents aged 12–17 years and the Child Inventory-4 (CI-4) in 493 children aged 8–11 years. Adolescents were questioned about experiences of HIV stigma. Caregiver psychological distress was assessed with the Self-Reporting Questionnaire (SRQ-20). Linear regression models were applied to identify variables associated with discrepancy scores. Results: Self-reported emotional problems (EPs) were present in 28.8% of adolescents and 36.9% of children, and 14.5% of adolescents self-reported behavioral problems (BPs). There was only a modest correlation (r ≤ 0.29) between caregiver- and CA-HIV-reported EBPs, with caregivers reporting more EPs whereas adolescents reported more BPs. Informant discrepancy between adolescents and caregivers for BPs was associated with adolescent age and caregiver’s employment and HIV status. Among adolescents, EP discrepancy scores were associated with adolescent’s WHO HIV clinical stage, caregiver level of education, and caregivers caring for other children. Among children, EP discrepancy scores were associated with child and caregiver age, caregiver level of education, and caregiver self-rated health status. HIV stigma and caregiver psychological distress were also associated with discrepancy, such that adolescents who experienced HIV stigma rated their EPs as more severe than their caregivers did and caregivers with increased psychological distress rated EBPs as more severe than CA-HIV self-rated. Conclusions: EBPs are frequently endorsed by CA-HIV, and agreement between informants is modest. Informant discrepancy is related to unique psychosocial and HIV-related factors. Multi-informant reports enhance the evaluation of CA-HIV and informant discrepancies can provide additional insights into the mental health of CA-HIV.

How Monocytes Contribute to Increased Risk of Atherosclerosis in Virologically-Suppressed HIV-Positive Individuals Receiving Combination Antiretroviral Therapy.

Combination antiretroviral therapy (ART) is effective at suppressing HIV viremia to achieve persistently undetectable levels in peripheral blood in the majority of individuals with access and ability to maintain adherence to treatment. However, evidence suggests that ART is less effective at eliminating HIV-associated inflammation and innate immune activation. To the extent that residual inflammation and immune activation persist, virologically suppressed people living with HIV (PLWH) may have increased risk of inflammatory co-morbidities, and adjunctive therapies may need to be considered to reduce HIV-related inflammation and fully restore the health of virologically suppressed HIV+ individuals. Cardiovascular disease (CVD) is the single leading cause of death in the developed world and is becoming more important in PLWH with access to ART. Arterial disease due to atherosclerosis, leading to acute myocardial infarction (AMI) and stroke, is a major component of CVD. Atherosclerosis is an inflammatory disease, and epidemiological comparisons of atherosclerosis and AMI show a higher prevalence and suggest a greater risk in PLWH compared to the general population. The reasons for greater prevalence of CVD in PLWH can be broadly grouped into four categories: (a) the higher prevalence of traditional risk factors e.g., smoking and hypertension (b) dyslipidemia (also a traditional risk factor) caused by off-target effects of ART drugs (c) HIV-related inflammation and immune activation and (d) other undefined HIV-related factors. Management strategies aimed at reducing the impact of traditional risk factors in PLWH are similar to those for the general population and their effectiveness is currently being evaluated. Together with improvements in ART regimens and guidelines for treatment, and a greater awareness of its impact on CVD, the HIV-related risk of AMI and stroke is decreasing but remains elevated compared to the general community. Monocytes are key effector cells which initiate the formation of atherosclerotic plaques by migrating into the intima of coronary arteries and accumulating as foam cells full of lipid droplets. This review considers the specific role of monocytes as effector cells in atherosclerosis which progresses to AMI and stroke, and explores mechanisms by which HIV may promote an atherogenic phenotype and function independent of traditional risk factors. Altered monocyte function may represent a distinct HIV-related factor which increases risk of CVD in PLWH.