Subclinical Atherosclerosis Across the Menopausal Transition in Women With and Without HIV.

The menopausal transition is a pivotal time of cardiovascular risk, but knowledge is limited in HIV. We studied longitudinal carotid artery intima-media thickness (CIMT) in the Women's Interagency HIV Study (2004-2019; 979 women/3247 person-visits; 72% with HIV). Among women with HIV only, those who transitioned had greater age-related CIMT progression compared to those remaining premenopausal (difference in slope = 1.64 µm/year, P = .002); and CIMT increased over time in the pretransition (3.47 µm/year, P = .002) and during the menopausal transition (9.41 µm/year, P < .0001), but not posttransition (2.9 µm/year, P = .19). In women with HIV, menopause may accelerate subclinical atherosclerosis as measured by CIMT.

Life course history of physical and sexual abuse is associated with cardiovascular disease risk among women living with and without HIV.

OBJECTIVE: Sexual and physical abuse predict cardiovascular disease (CVD) among women in the general population. Women living with HIV (WLWH) report more abuse and have higher CVD risk compared with other women, yet associations between abuse history and CVD have not been considered among WLWH. This study fills this gap, and describes possible pathways linking abuse to CVD risk among WLWH and women living without HIV (WLWOH). METHODS: Using 25 years of data from the Women's Interagency HIV Study (WIHS; n  = 2734; WLWH n  = 1963; WLWOH n  = 771), we used longitudinal generalized estimating equations (GEE) to test associations between sexual and physical abuse with CVD risk. Framingham (FRS-H) and the American College of Cardiology/American Heart Association-Pooled Cohort Equation (ACC/AHA-PCE) scores were examined. Analyses were stratified by HIV-serostatus. RESULTS: Among WLWH, childhood sexual abuse was associated with higher CVD risk ( ßFRS-H  = 1.25, SE = 1.08, P  = 0.005; ßACC/AHA-PCE  = 1.14, SE = 1.07, P  = 0.04) compared with no abuse. Adulthood sexual abuse was associated with higher CVD risk for WLWH ( ßFRS-H  = 1.39, SE = 1.08, P  < 0.0001) and WLWOH ( ßFRS-H  = 1.58, SE = 1.14, P  = 0.0006). Childhood physical abuse was not associated with CVD risk for either group. Adulthood physical abuse was associated with CVD risk for WLWH ( ßFRS-H  = 1.44, SE = 1.07; P  < 0.0001, ßACC/AHA-PCE  = 1.18, SE = 1.06, P  = 0.002) and WLWOH ( ßFRS-H  = 1.68, SE = 1.12, P  < 0.0001; ßACC/AHA-PCE  = 1.24, SE = 1.11, P  = 0.03). Several pathway factors were significant, including depression, smoking, and hepatitis C infection. CONCLUSION: Life course abuse may increase CVD risk among WLWH and women at high risk of acquiring HIV. Some comorbidities help explain the associations. Assessing abuse experiences in clinical encounters may help contextualize cardiovascular risk among this vulnerable population and inform intervention.

Hypertension burden, treatment, and control among people with HIV at a clinical care center in the Southeastern US, 2014-2019.

Hypertension management outcomes in people with HIV (PWH) are not well characterized, despite high hypertension burden. We assessed hypertension prevalence, incidence, treatment, and outcomes among patients with HIV at a clinical center in the southeastern US, from 2014 to 2019. To identify characteristics associated with treatment and outcomes, we estimated adjusted risk ratios (aRR) and 95% confidence intervals (CI). Among 2274 patients, 72% were cisgender men, 56% non-Hispanic Black, median age 47 years, 48% MSM, 12% had CD4 cell count <200 cells/µl, 72% HIV RNA level <400 copies/mL and 39% prevalent hypertension. Hypertension incidence rate was 6.3/100 person-years (95% CI, 5.6-7.0). Among incident hypertension cases (n = 275), 16% (95% CI, 11-20) initiated an antihypertensive within one year. Compared to non-Hispanic white patients, Hispanic (aRR, 6.68; 95% CI, 1.50-29.74) and non-Hispanic Black patients (aRR, 2.18; 95% CI, 0.91-5.24) were more likely to initiate an antihypertensive. Among patients initiating an antihypertensive (n = 178), 63% (95% CI 56-70) experienced blood pressure control within one year. Patients with HIV experienced a high burden of hypertension with notable delays in antihypertensive initiation, as well as gaps in achieving blood pressure control, highlighting opportunities for interventions designed to minimize delays in controlling hypertension in this vulnerable population.

Elevated CD4 + T-cell glucose metabolism in HIV+ women with diabetes mellitus.

OBJECTIVE: Immune dysfunction and chronic inflammation are characteristic of HIV infection and diabetes mellitus, with CD4 + T-cell metabolism implicated in the pathogenesis of each disease. However, there is limited information on CD4 + T-cell metabolism in HIV+ persons with diabetes mellitus. We examined CD4 + T-cell glucose metabolism in HIV+ women with and without diabetes mellitus. DESIGN: A case-control study was used to compare CD4 + T-cell glucose metabolism in women with HIV with or without diabetes mellitus. METHODS: Nondiabetic (HIV+DM-, N = 20) or type 2 diabetic HIV+ women with (HIV+DM+, N  = 16) or without (HIV+DMTx+, N  = 18) antidiabetic treatment were identified from the WIHS and matched for age, race/ethnicity, smoking status and CD4 + cell count. CD4 + T-cell immunometabolism was examined by flow cytometry, microfluidic qRT-PCR of metabolic genes, and Seahorse extracellular flux analysis of stimulated CD4 + T cells. RESULTS: HIV+DM+ displayed a significantly elevated proportion of CD4 + T cells expressing the immunometabolic marker GLUT1 compared with HIV+DMTx+ and HIV+DM- ( P  = 0.04 and P  = 0.01, respectively). Relative expression of genes encoding key enzymes for glucose metabolism pathways were elevated in CD4 + T cells of HIV+DM+ compared with HIV+DMTx+ and HIV+DM-. T-cell receptor (TCR)-activated CD4 + T cells from HIV+DM+ showed elevated glycolysis and oxidative phosphorylation compared with HIV+DM-. CONCLUSION: CD4 + T cells from HIV+DM+ have elevated glucose metabolism. Treatment of diabetes mellitus among women with HIV may partially correct CD4 + T-cell metabolic dysfunction.

Polypharmacy Is Associated With Falls in Women With and Without HIV.

BACKGROUND: Aging in people with HIV is associated with increased risk of developing synergistic conditions such as neurocognitive impairment, polypharmacy, and falls. We assessed associations between polypharmacy (use of 5 or more non-ART medications), use of neurocognitive adverse effects (NCAE) medications, and odds of falls in women with HIV (WWH) and without HIV (HIV-). METHODS: Self-reported falls and medication use data were contributed semiannually by 1872 (1315 WWH and 557 HIV-) Women's Interagency HIV Study participants between 2014 and 2016. Polypharmacy and NCAE medication use were evaluated separately and jointly in multivariable models to assess their independent contributions to single and multiple falls risk. RESULTS: The proportion of women who reported any fall was similar by HIV status (19%). WWH reported both greater polypharmacy (51% vs. 41%; P < 0.001) and NCAE medication use (44% vs. 37%; P = 0.01) than HIV- women. Polypharmacy conferred elevated odds of single fall [adjusted odds ratio (aOR) 1.67, 95% CI: 1.36 to 2.06; P < 0.001] and multiple falls (aOR 2.31, 95% CI: 1.83 to 2.93; P < 0.001); the results for NCAE medications and falls were similar. Both polypharmacy and number of NCAE medications remained strongly and independently associated with falls in multivariable models adjusted for HIV serostatus, study site, sociodemographics, clinical characteristics, and substance use. CONCLUSIONS: Polypharmacy and NCAE medication use were greater among WWH compared with HIV-, and both were independently and incrementally related to falls. Deprescribing and avoidance of medications with NCAEs may be an important consideration for reducing fall risk among WWH and sociodemographically similar women without HIV.

Stable Latent HIV Infection and Low-level Viremia Despite Treatment With the Broadly Neutralizing Antibody VRC07-523LS and the Latency Reversal Agent Vorinostat.

We tested the combination of a broadly neutralizing HIV antibody with the latency reversal agent vorinostat (VOR). Eight participants received 2 month-long cycles of VRC07-523LS with VOR. Low-level viremia, resting CD4+ T-cell-associated HIV RNA (rca-RNA) was measured, and intact proviral DNA assay (IPDA) and quantitative viral outgrowth assay (QVOA) were performed at baseline and posttreatment. In 3 participants, IPDA and QVOA declines were accompanied by significant declines of rca-RNA. However, no IPDA or QVOA declines clearly exceeded assay variance or natural decay. Increased resistance to VRC07-523LS was not observed. This combination therapy did not reduce viremia or the HIV reservoir. Clinical Trials Registration. NCT03803605.

Addressing and Inspiring Vaccine Confidence in Black, Indigenous, and People of Color During the Coronavirus Disease 2019 Pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, we have witnessed profound health inequities suffered by Black, Indigenous, and People of Color (BIPOC). These manifested as differential access to testing early in the pandemic, rates of severe disease and death 2-3 times higher than white Americans, and, now, significantly lower vaccine uptake compared with their share of the population affected by COVID-19. This article explores the impact of these COVID-19 inequities (and the underlying cause, structural racism) on vaccine acceptance in BIPOC populations, ways to establish trustworthiness of healthcare institutions, increase vaccine access for BIPOC communities, and inspire confidence in COVID-19 vaccines.

Assessment of Coronary Artery Disease With Computed Tomography Angiography and Inflammatory and Immune Activation Biomarkers Among Adults With HIV Eligible for Primary Cardiovascular Prevention.

Importance: Cardiovascular disease (CVD) is increased among people with HIV (PWH), but little is known regarding the prevalence and extent of coronary artery disease (CAD) and associated biological factors in PWH with low to moderate traditional CVD risk. Objectives: To determine unique factors associated with CVD in PWH and to assess CAD by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation. Design, Setting, and Participants: This cohort study among male and female PWH, aged 40 to 75 years, without known CVD, receiving stable antiretroviral therapy, and with low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to the 2013 American College of Cardiology/American Heart Association pooled cohort equation, was part of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH conducted at 31 US sites. Participants were enrolled from May 2015 to February 2018. Data analysis was conducted from May to December 2020. Exposure: HIV disease. Main Outcomes and Measures: The primary outcome was the prevalence and composition of CAD assessed by coronary CTA and, secondarily, the association of CAD with traditional risk indices and circulating biomarkers, including insulin, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP). Results: The sample included 755 participants, with a mean (SD) age of 51 (6) years, 124 (16%) female participants, 267 (35%) Black or African American participants, 182 (24%) Latinx participants, a low median (interquartile range) ASCVD risk (4.5% [2.6%-6.8%]), and well-controlled viremia. Overall, plaque was seen in 368 participants (49%), including among 52 of 175 participants (30%) with atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at least 50% was rare (25 [3%]), but vulnerable plaque and high Leaman score (ie, >5) were more frequently observed (172 of 755 [23%] and 118 of 743 [16%], respectively). Overall, 251 of 718 participants (35%) demonstrated coronary artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels were higher in those with plaque compared with those without (eg, median [IQR] IL-6 level, 1.71 [1.05-3.04] pg/mL vs 1.45 [0.96-2.60] pg/mL; P = .008). LpPLA2 and IL-6 levels were associated with plaque in adjusted modeling, independent of traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 95% CI, 1.02-1.12; P = .01). Conclusions and Relevance: In this study of a large primary prevention cohort of individuals with well-controlled HIV and low to moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable plaque, was highly prevalent. Participants with plaque demonstrated higher levels of immune activation and arterial inflammation, independent of traditional ASCVD risk and HIV parameters.

Indoleamine 2,3 dioxygenase, age, and immune activation in people living with HIV.

Immune activation complicates HIV despite antiretroviral therapy (ART). Indoleamine 2,3 dioxygenase (IDO) catabolizes tryptophan (T) to kynurenine (K), regulating immune activity, and IDO activity increases with age. This study examines the relationship of IDO activity, bacterial translocation, and aging in people living with HIV (PLWH) on ART. Samples and data from PLWH on ART from the Centers for AIDS Research Network of Integrated Clinical Systems and from matched HIV-uninfected patients (controls) from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study were analyzed. The ratio of K to T (K:T) and neopterin were indicators of inflammation; 16S ribosomal DNA (16S rDNA) and lipopolysaccharide (LPS) were markers of bacterial translocation. Samples and data from 205 PLWH and 99 controls were analyzed. PLWH had higher K:T values across all ages, with a significant relationship between age and K:T for both groups. CD4 count or CD4 nadir had no association with K:T. There was no positive association between level of 16S rDNA or LPS detection and K:T. K:T and neopterin were associated. PLWH had elevated IDO activity, at younger ages, despite ART. This study suggests K:T ratio increases with age in both groups and is elevated in PLWH at all ages compared with age-matched controls.

High Frequency of Recurrent Falls Among Prefrail and Frail Women With and Without HIV.

BACKGROUND: Frailty may occur at younger ages among HIV+ populations. We evaluated associations of the frailty status with self-reported single and recurrent falls in the Women's Interagency HIV Study (WIHS). METHODS: The frailty status was defined using the Fried Frailty Phenotype (FFP) among 897 HIV+ and 392 HIV- women; median age 53 years. Women were classified as robust (FFP 0), prefrail (FFP 1-2), and frail (FFP 3-5). Stepwise logistic regression models adjusting for the HIV status and study site were fit to evaluate associations of the FFP with self-reported single (1 vs. 0) and recurrent falls (≥2 vs. 0) over the prior 12 months. RESULTS: HIV+ women were less likely to be frail (9% vs. 14% vs. P = 0.009), but frequency of falls did not differ by the HIV status. In multivariate analyses, recurrent falls were more common among prefrail [adjusted odds ratio (AOR) 2.23, 95% confidence interval (CI): 1.40 to 3.57, P = 0.0008] and frail (AOR 3.61, 95% CI: 1.90 to 6.89, P < 0.0001) than robust women. Among HIV+ women, single (AOR 2.88, 95% CI: 1.16 to 7.20, P = 0.023) and recurrent falls (AOR 3.50, 95% CI: 1.24 to 9.88, P = 0.018) were more common among those who were frail; recurrent, but not single falls, were more common among prefrail than robust HIV+ women (AOR 2.00, 95% CI: 1.03 to 3.91, P = 0.042). CONCLUSIONS: HIV+ women were less likely to be frail. Compared with robust women, prefrail and frail women with and without HIV were more likely to experience single or recurrent falls within a 12-month period. Additional studies are needed to develop interventions that decrease development of frailty and reduce risk of recurrent falls among HIV+ women.

Innovations in Human Immunodeficiency Virus (HIV) Care Delivery During the Coronavirus Disease 2019 (COVID-19) Pandemic: Policies to Strengthen the Ending the Epidemic Initiative-A Policy Paper of the Infectious Diseases Society of America and the HIV Medicine Association.

The goal of the Ending the HIV Epidemic Initiative is to reduce new infections in the United States by 90% by 2030. Success will require fundamentally changing human immunodeficiency virus (HIV) prevention and care delivery to engage more persons with HIV and at risk of HIV in treatment. While the coronavirus disease 2019 (COVID-19) pandemic reduced in-person visits to care facilities and led to concern about interruptions in care, it also accelerated growth of alternative options, bolstered by additional funding support. These included the use of telehealth, medication delivery to the home, and increased flexibility facilitating access to Ryan White HIV/AIDS Program services. While the outcomes of these programs must be studied, many have improved accessibility during the pandemic. As the pandemic wanes, long-term policy changes are needed to preserve these options for those who benefit from them. These new care paradigms may provide a roadmap for progress for those with other chronic health issues as well.

Impaired Cognition Predicts Falls Among Women With and Without HIV Infection.

OBJECTIVE: To determine whether domain-specific neurocognitive (NC) impairments predict falls in HIV+ compared with HIV- women. DESIGN: Cross-sectional data analysis from 825 HIV+ and 392 HIV- women in the Women's Interagency HIV Study with NC testing within 2 years before falls surveys. METHODS: NC impairment (T score <40) was assessed in 7 domains: executive function, psychomotor speed, attention, learning, memory, fluency, and fine motor function. For domains associated with any fall within 6 months in simple logistic regression (P < 0.05), hierarchical regression models evaluated associations between NC impairment and odds of falling, adjusting for: (1) study site and HIV, (2) demographics, (3) comorbid conditions, (4) substance use/central nervous system active medications, and HIV-specific factors. RESULTS: Median age was higher in HIV+ than HIV- women (51 vs. 48 yrs); prevalence of falls was similar (19% HIV+, 16% HIV-). Overall, executive function [OR (odds ratio) = 1.82, 95% CI (confidence interval): 1.21 to 2.74; P = 0.004], psychomotor speed (OR = 1.59, 95% CI: 1.05 to 2.42, P = 0.03), and fine motor (OR 1.70, 95% CI: 1.11 to 2.61, P = 0.02) impairments were associated with greater odds of falls in fully adjusted models. In fully adjusted models, associations of executive function, psychomotor speed, and fine motor were nonsignificant among HIV+ women; conversely, among HIV- women, associations with impaired executive and fine motor functions were strengthened and remained significant. CONCLUSIONS: Cognitive impairment was associated with falls among middle-aged HIV- but not HIV+ women. Additional studies should elucidate mechanisms by which domain-specific NC impairment impacts fall risk among older HIV+ and HIV- women and how different factors modify relationships between cognition and falls.

Computerized Adjudication of Coronary Heart Disease Events Using the Electronic Medical Record in HIV Clinical Research: Possibilities and Challenges Ahead.

This pilot study assessed feasibility of computer-assisted electronic medical record (EMR) abstraction to ascertain coronary heart disease (CHD) event hospitalizations. We included a sample of 87 hospitalization records from participants the University of North Carolina (UNC) site of the Women's Interagency HIV Study (WIHS) and UNC Center for AIDS Research (CFAR) HIV Clinical Cohort who were hospitalized within UNC Healthcare System from July 2004 to July 2015. We compared a computer algorithm utilizing diagnosis/procedure codes, medications, and cardiac enzyme levels to adjudicate CHD events [myocardial infarction (MI)/coronary revascularization] from the EMR to standardized manual chart adjudication. Of 87 hospitalizations, 42 were classified as definite, 25 probable, and 20 non-CHD events by manual chart adjudication. A computer algorithm requiring presence of ≥1 CHD-related International Classification of Diseases, 9th Revision (ICD-9)/Current Procedural Terminology (CPT) code correctly identified 24 of 42 definite (57%), 29 of 67 probable/definite CHD (43%), and 95% of non-CHD events; additionally requiring clinically defined cardiac enzyme levels or administration of MI-related medications correctly identified 55%, 42%, and 95% of such events, respectively. Requiring any one of the ICD-9/CPT or cardiac enzyme criteria correctly identified 98% of definite, 97% of probable/definite CHD, and 85% of non-CHD events. Challenges included difficulty matching hospitalization dates, incomplete diagnosis code data, and multiple field names/locations of laboratory/medication data. Computer algorithms comprising only ICD-9/CPT codes failed to identify a sizable proportion of CHD events. Using a less restrictive algorithm yielded fewer missed events but increased the false-positive rate. Despite potential benefits of EMR-based research, there remain several challenges to fully computerized adjudication of CHD events.

A Randomized, Double-blinded, Placebo-controlled Trial of Sitagliptin for Reducing Inflammation and Immune Activation in Treated and Suppressed Human Immunodeficiency Virus Infection.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have pleotropic anti-inflammatory and immune regulatory effects in addition to glucoregulation. We evaluated inflammation and immune markers in suppressed human immunodeficiency virus (HIV) infection during treatment with the DPP-4 inhibitor sitagliptin. METHODS: Virologically suppressed adults with HIV without diabetes on stable antiretroviral therapy (ART) with ≥100/µL CD4 cells were randomized to 16 weeks of sitagliptin 100 mg/day vs placebo in a multicenter trial. The primary endpoint was the change in plasma soluble CD14 (sCD14) from baseline to week 15-16. RESULTS: Ninety participants were randomized, and 42 from each arm were included in per-protocol analyses. Participants were 45% non-Hispanic white, 38% non-Hispanic black, and 15% Hispanic, with a median age of 51 years; 83% were male; and the median CD4 count was 602 cells/µL. At week 15-16, there was no difference in sCD14 change between the 2 arms (P = .69). Relative to placebo, the sitagliptin arm had 47% greater decline in CXCL10 (95% confidence interval, -57% to -35%) at week 15 (P < .001). There were no significant between-arm differences in other soluble biomarkers, total CD4 and CD8 counts, or markers of lymphocyte or monocyte activation. Sitagliptin was well tolerated. CONCLUSIONS: Sixteen weeks of sitagliptin had no effect on sCD14 levels in virologically suppressed participants with HIV. CXCL10, a chemokine involved in atherogenesis that predicts non-AIDS events during ART, declined markedly with sitagliptin. This suggests that DPP-4 inhibition has the potential to reduce cardiovascular morbidity in treated HIV infection. CLINICAL TRIALS REGISTRATION: NCT01426438.

Low-density lipoprotein cholesterol response after statin initiation among persons living with human immunodeficiency virus.

BACKGROUND: Meta-analyses of general population studies report mean low-density lipoprotein cholesterol (LDL-C) reductions of 30% to <50% with moderate-intensity and ≥50% with high-intensity statins. Persons living with human immunodeficiency virus (PLWH) are at high risk for atherosclerotic cardiovascular disease (ASCVD), yet many have elevated LDL-C. OBJECTIVE: To evaluate LDL-C response after statin initiation among PLWH. METHODS: We conducted a retrospective cohort study of PLWH initiating statins between 2009 and 2013 (N = 706). Patients were categorized into mutually exclusive groups in the following hierarchy: history of coronary heart disease (CHD), diabetes, prestatin LDL-C ≥190 mg/dL, 10-year predicted ASCVD risk ≥7.5%, and none of the above (ie, unknown statin indication). The primary outcome was a ≥30% reduction in LDL-C after statin initiation. RESULTS: Among patients initiating statins, 5.8% had a history of CHD, 13.6% had diabetes, 6.2% had LDL-C ≥190 mg/dL, 35.4% had 10-year ASCVD risk ≥7.5%, and 39.0% had an unknown statin indication. Among patients with a history of CHD, 31.7% achieved a ≥30% LDL-C reduction compared with 25.0%, 59.1%, and 33.9% among those with diabetes, LDL-C ≥190 mg/dL, and 10-year ASCVD risk ≥7.5%, respectively. In multivariable adjusted analyses and compared to patients with an unknown statin indication, LDL-C ≥ 190 mg/dL was associated with a prevalence ratio for an LDL-C reduction ≥30% of 1.81 (95% confidence interval, 1.34-2.45), whereas no statistically significant association was present for history of CHD, diabetes, and 10-year ASCVD risk ≥7.5%. CONCLUSION: A low percentage of PLWH achieved the expected reductions in LDL-C after statin initiation, highlighting an unmet need for ASCVD risk reduction.

Longitudinal study of falls among HIV-infected and uninfected women: the role of cognition.

BACKGROUND: Although fracture rates are higher in HIV+ than HIV- women, whether HIV infection increases risk of falls is unclear. We determined the longitudinal occurrence and risk factors for falls in the Women's Interagency HIV Study (WIHS), and explored associations with cognitive complaints. METHODS: Recent (prior 6 months) self-reported falls were collected in 1,816 (1,250 HIV+; 566 HIV-) women over 24 months. Generalized estimating equation models using stepwise selection determined odds of any fall (versus none). RESULTS: HIV+ women were older than HIV- women (median 49 versus 47 years; P=0.0004), more likely to report neuropathy (20% versus 16%; P=0.023), and had greater central nervous system (CNS) medication use. At least one fall was reported in 41% HIV+ versus 42% HIV- women, including ≥2 falls in 25% HIV+ and 24% HIV- (overall P=0.30). Cognitive complaints were associated with falls among HIV+ (odds ratio [OR] 2.38; 95% CI 1.83, 3.09) and HIV- women (OR 3.43; 95% CI 2.37, 4.97); in adjusted models, cognitive complaints remained significant only in HIV- women (adjusted [aOR] 2.26; 95% CI 1.46, 3.48). Factors associated with any fall in adjusted analyses included: depressive symptoms and neuropathy (both HIV+ and HIV-); age, marijuana use, multiple CNS medications, and HCV infection (HIV+ only); and cognitive complaints, quality of life, hypertension and obesity (HIV- only). CONCLUSIONS: Middle-aged HIV+ and HIV- women had similar fall rates. Among HIV+ women, factors affecting cognition such as age, depressive symptoms, marijuana use and multiple CNS medications were important predictors of falls, however, cognitive complaints were not.

Genome-wide admixture and association study of subclinical atherosclerosis in the Women's Interagency HIV Study (WIHS).

Cardiovascular disease (CVD) is a major comorbidity among HIV-infected individuals. Common carotid artery intima-media thickness (cCIMT) is a valid and reliable subclinical measure of atherosclerosis and is known to predict CVD. We performed genome-wide association (GWA) and admixture analysis among 682 HIV-positive and 288 HIV-negative Black, non-Hispanic women from the Women's Interagency HIV study (WIHS) cohort using a combined and stratified analysis approach. We found some suggestive associations but none of the SNPs reached genome-wide statistical significance in our GWAS analysis. The top GWAS SNPs were rs2280828 in the region intergenic to mediator complex subunit 30 and exostosin glycosyltransferase 1 (MED30 | EXT1) among all women, rs2907092 in the catenin delta 2 (CTNND2) gene among HIV-positive women, and rs7529733 in the region intergenic to family with sequence similarity 5, member C and regulator of G-protein signaling 18 (FAM5C | RGS18) genes among HIV-negative women. The most significant local European ancestry associations were in the region intergenic to the zinc finger and SCAN domain containing 5D gene and NADH: ubiquinone oxidoreductase complex assembly factor 1 (ZSCAN5D | NDUF1) pseudogene on chromosome 19 among all women, in the region intergenic to vomeronasal 1 receptor 6 pseudogene and zinc finger protein 845 (VN1R6P | ZNF845) gene on chromosome 19 among HIV-positive women, and in the region intergenic to the SEC23-interacting protein and phosphatidic acid phosphatase type 2 domain containing 1A (SEC23IP | PPAPDC1A) genes located on chromosome 10 among HIV-negative women. A number of previously identified SNP associations with cCIMT were also observed and included rs2572204 in the ryanodine receptor 3 (RYR3) and an admixture region in the secretion-regulating guanine nucleotide exchange factor (SERGEF) gene. We report several SNPs and gene regions in the GWAS and admixture analysis, some of which are common across HIV-positive and HIV-negative women as demonstrated using meta-analysis, and also across the two analytic approaches (i.e., GWA and admixture). These findings suggest that local European ancestry plays an important role in genetic associations of cCIMT among black women from WIHS along with other environmental factors that are related to CVD and may also be triggered by HIV. These findings warrant confirmation in independent samples.

Increased glucose transporter-1 expression on intermediate monocytes from HIV-infected women with subclinical cardiovascular disease.

OBJECTIVE: People living with HIV (PLWH) have chronic immune activation and increased cardiovascular disease (CVD) risk. Activation of monocytes and T lymphocytes causes upregulation of glucose transporter-1 (GLUT1) for efficient function. PLWH have an increased percentage of GLUT1-expressing monocytes and T lymphocytes, but it is unclear if these cells are associated with CVD. We evaluated the expression of GLUT1 and CD38 on monocyte and T lymphocyte populations from HIV-infected women with subclinical CVD. METHODS: Participants with more than 75th percentile (n = 15) and less than 25th percentile (n = 15) age-adjusted intima-media thickness (IMT) at the right common carotid artery and bifurcation were identified from the Women's Interagency HIV Study. Groups were matched by age, race/ethnicity, smoking status, and CD4 cell count. All women were receiving suppressive antiretroviral therapy except for one high and one low IMT participant. Monocyte and T lymphocyte populations were evaluated for GLUT1 and CD38 expression using flow cytometry. RESULTS: Intermediate monocytes from high IMT women had significantly increased expression of GLUT1 (310 MFI vs. 210 MFI, P = 0.024) (66.4% vs. 48.5%, P = 0.031) and CD38 (339 MFI vs. 211 MFI, P = 0.002) (10.5% vs. 3.8%, P = 0.0002) compared with women with low IMT. High and low IMT participants showed no differences in GLUT1 or CD38 expression on classical monocytes, nonclassical monocytes, CD4 and CD8 T lymphocytes. CONCLUSION: GLUT1-expressing intermediate monocytes are elevated in HIV-infected women with subclinical CVD. These cells may contribute to development of CVD in PLWH and could be a novel target to limit inflammation.

Falls among middle-aged women in the Women's Interagency HIV Study.

BACKGROUND: To determine the frequency and risk factors for falls among middle-aged HIV+ and HIV- women in the Women's Interagency HIV Study (WIHS). METHODS: We quantified self-report of any and multiple (≥2) falls in the prior 6 months among 1,412 HIV+ and 650 HIV- women with mean age 48 years. Logistic regression was used to evaluate associations of demographics, behavioural factors, comorbid conditions and medications with odds of any fall (versus none) and multiple falls (versus ≤1 fall). RESULTS: At least one fall was reported in 263 HIV+ (19%) versus 119 HIV- (18%) women, and ≥2 falls reported in 133 HIV+ (9%) versus 65 HIV- (10%) women. HIV infection was not associated with falls in multivariate analyses. Factors independently associated with any fall included age (adjusted odds ratio [aOR] 1.71, 95% CI 1.17, 2.49 age 50-59 versus <39 years; aOR 2.26, 95% CI 1.38, 3.71 age ≥60 versus <39), current marijuana use (aOR 2.19, 95% CI 1.53, 3.13) depressive symptoms (aOR 1.57, 95% CI 1.21, 2.05 for Center for Epidemiology Studies Depression score ≥16), subjective cognitive complaints (aOR 2.19, 95% CI 1.56, 3.08), neuropathy (aOR 1.59, 95% CI 1.19, 2.13), obesity (aOR 1.39, 95% CI 1.08, 1.80), number of central nervous system active agents (aOR 2.98, 95% CI 1.90, 4.68 for ≥3 agents versus 0) and WIHS site. Factors associated with ≥2 falls included age, marijuana use, number of central nervous system active agents, subjective cognitive complaints, depressive symptoms, neuropathy and study site. CONCLUSIONS: Falls were associated with factors affecting cognition, but not HIV status in this large cohort of women. Longitudinal studies are needed to determine the incidence and consequences of falls by HIV status as women age.