Prevalence and 1-year incidence of frailty among women with and without HIV in the Women's Interagency HIV Study

A previous cross-sectional analysis of 2028 women in the Women’s Interagency HIV Study (WIHS), who were on average 39 years old, found a frailty prevalence of 17% and 10% in women with or at risk for HIV, respectively [1]. To our knowledge, the only two longitudinal studies of frailty among people with HIV were conducted in the Multicenter AIDS Cohort Study (MACS), which includes only men [2,3]. Data on the distribution of frailty components are limited, and have not been reported for HIV-seropositive people in the United State

The clinical profile of moderate amblyopia in children younger than 7 years

Objective To describe the demographic and clinical characteristics of a cohort of children with moderate amblyopia participating in the Amblyopia Treatment Study 1, a randomized trial comparing atropine and patching. Methods The children enrolled were younger than 7 years and had strabismic, anisometropic, or combined strabismic and anisometropic amblyopia. Visual acuity, measured with a standardized testing protocol using single-surround HOTV optotypes, was 20/40 to 20/100 in the amblyopic eye, with an intereye acuity difference of 3 or more logMAR lines. There were 419 children enrolled, 409 of whom met these criteria and were included in the analyses. Results The mean age of the 409 children was 5.3 years. The cause of the amblyopia was strabismus in 38%, anisometropia in 37%, and both strabismus and anisometropia in 24%. The mean visual acuity of the amblyopic eyes (approximately 20/60) was similar among the strabismic, anisometropic, and combined groups (P = .24), but visual acuity of the sound eyes was worse in the strabismic group compared with the anisometropic group (P<.001). For the patients randomized into the patching group, 43% were initially treated for 6 hours per day, whereas 17% underwent full-time patching. Patients with poorer visual acuity in the amblyopic eye were prescribed more hours of patching than patients with better acuity (P = .003). Conclusions In the Amblyopia Treatment Study 1, there were nearly equal proportions of patients with strabismic and anisometropic amblyopia. A similar level of visual impairment was found irrespective of the cause of amblyopia. There was considerable variation in treatment practices with regard to the number of hours of initial patching prescribed

Hormone therapy and fractures in postmenopausal women

Background:Fracture rates have been reported to be higher among older women living with HIV (WLWH) than HIV- women. Hormone therapy with estrogen can reduce vasomotor symptoms (VMS) associated with menopause and prevent fractures. As data are limited on the benefits of hormone therapy use in WLWH, we examined associations of hormone therapy, use and fractures.Methods:A prospective study of 1765 (1350 WLWH and 415 HIV-) postmenopausal Women's Interagency HIV Study (WIHS) participants was performed, including self-reported hormone therapy, use and fracture data from 2003 to 2017. Proportional hazard models determined predictors of new fractures at any site or at typical fragility fracture sites (hip, spine, wrist).Results:At the first postmenopausal visit, the median (IQR) age of WLWH was slightly younger than HIV- women [49.8 (46.4-53) vs. 50.7 (47.5-54), P = 0.0002] and a smaller proportion of WLWH reported presence of VMS (17% vs. 26%, P < 0.0001). A greater proportion of WLWH than HIV- women reported hormone therapy use (8% vs. 4%, P = 0.007) at the first postmenopausal visit. In multivariate analyses, white race and smoking were significant predictors of incident fracture at any site but hormone therapy (P = 0.69) and HIV status (P = 0.53) were not.Conclusion:Our study did not find evidence of benefit or harm with regards to fracture outcomes in postmenopausal WLWH receiving hormone therapy. Further research is needed to determine whether hormone therapy has benefits beyond treatment of VMS, such as prevention of adverse aging-associated outcomes

Midlife body mass index, central adiposity and neuropsychological performance over 10 years in women living with and without HIV

Background and objective: Observations of overweight and obesity in association with neuropsychological performance (NP) vary over the adult life course depending on baseline levels, biological sex, age, race, temporality of measurements, and other factors. Therefore, similar published analyses across cohorts are inconsistent. In our sample of women living with HIV (WLWH) and women without HIV (WWOH), we conducted comparable analyses as those published in men with and without HIV. We examined cross-sectional and longitudinal associations between body mass index (BMI) and waist circumference (WC) and NP. Methods: Four hundred thirty two 432 virologically-suppressed WLWH and 367 WWOH, ≥40 years in the Women’s Interagency HIV Study (WIHS) with anthropometry and NP assessments every two years from 2009-2019 were included in the study. Demographically-adjusted T-scores were calculated for six NP domains: learning, memory, executive function, processing speed, attention and working memory, and motor function. Multivariable linear regression models stratified by HIV status were used to examine cross-sectional associations of BMI and WC by NP domain; repeated measures analyses assessed baseline BMI and WC in association with longitudinal change in NP. Covariates included sociodemographic, behavioral, and HIV-related characteristics. Results: At baseline among all women, the median age was 45 years, 65% were Non-Latinx Black women, and 45% were obese women. Obese WLWH (BMI≥30.0 kg/m2) had poorer executive function (β=-2.27, 95%CI [-4.46, -0.07]) versus WLWH with healthy BMI (18.5–24.9 kg/m2). Longitudinally over ~8 years, obese versus overweight WWOH improved on memory (β=2.19, 95%CI [0.13, 4.26]), however overweight versus healthy WWOH experienced declining memory (β= -2.67, 95%CI [-5.40, -0.07]). Increasing WC was associated with declining executive, processing speed, and motor function (p’s<0.05); an at-risk WC was associated with improved memory (β=1.81, 95%CI [0.19, 3.44]) among WWOH. Among WLWH, increasing BMI was associated with improved learning (β=0.07, 95%CI [0.00, 0.15]. Conclusion: Our cross-sectional and longitudinal analyses evaluating the associations of BMI and WC and NP were mixed compared to previous reports. This illustrates the importance of sociodemographic characteristics, baseline levels of exposures and outcomes, HIV status, temporality of measurements, and other factors when evaluating aging HIV epidemiology study results

Weight and Body Mass Index Change after Switching to Integrase Inhibitors or Tenofovir Alafenamide among Women Living with HIV

Weight and body mass index (BMI) change was assessed among women after switch to integrase inhibitors (INSTIs) and/or tenofovir alafenamide (TAF). From 2006 to 2019, 1,458 women living with HIV enrolled in the Women's Interagency HIV Study and on antiretroviral therapy (ART) with ≥1 study visit before and after switching to INSTIs and/or TAF were included. Weight and BMI were compared pre- and postswitch to INSTI (by class and type) and/or TAF using multivariable linear mixed effects models; all models were also stratified by preswitch presence or absence of obesity (BMI ≥30 vs. <30 kg/m2). Mean age preswitch was 47 ± 6 years, 64% were black, mean CD4 = 475 ± 201 cells/mm3, 56% had HIV RNA <200 copies/mL, 36% switched to TAF but not INSTI, 60% to INSTI but not TAF, and 3.5% to TAF+INSTI. Time from pre- to postswitch was 12.8 ± 11.8 months. The INSTI-only group but not TAF groups had small but significant increases in weight and BMI: mean 79.2-80.6 kg and 30.2-30.7 kg/m2, p's < .001, respectively, with congruent findings by INSTI type (p's ≤ .01). In stratified (preswitch BMI) analyses, only nonobese subgroups experienced increases in weight and BMI across all ART treatment groups (p's < .05). Significant, although small-to-medium, increases in weight and BMI occurred among nonobese women who switched to INSTIs and/or TAF over short follow-up. Given long-term health consequences of obesity particularly as a low-grade inflammatory condition, identifying women at highest risk of ART-associated weight gain is imperative

White Blood Cell Counts, Lymphocyte Subsets, and Incident Diabetes Mellitus in Women Living with and without HIV

Diabetes mellitus (DM) is associated with expansion of proinflammatory lymphocyte subsets. We investigated the relationship of total white blood cell (WBC) count and lymphocyte subsets with incident DM in the Women's Interagency HIV Study (WIHS). Higher CD4 and CD8 T cell counts, lymphocyte count, and total WBC count were associated with incident DM among both women with and without HIV, although the association of CD8 was not statistically significant among women without HIV

Menopausal Hormone Therapy and Subclinical Cardiovascular Disease in Women With and Without Human Immunodeficiency Virus

Background: Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with human immunodeficiency virus (HIV), who have heightened immune activation and cardiovascular risks. Methods: Among 609 postmenopausal women (1234 person-visits) in the Women's Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis: carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004-2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors. Results: Women (mean age, 51 years; 80% HIV positive) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never-users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio, 0.57 [95% confidence interval {CI},. 40-.80]; P <. 01), 2.51 μm less progression of CIMT per year (95% CI, -4.60, to -.41; P =. 02), and marginally lower incidence of plaque over approximately 7 years (risk ratio, 0.38 [95% CI,. 14-1.03; P =. 06), compared with never-users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment. Conclusions: HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness