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/m
). Mean age preswitch was 47 ± 6 years, 64% were black, mean CD4 = 475 ± 201 cells/mm
, 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/m
,
s < .001, respectively, with congruent findings by INSTI type (
s ≤ .01). In stratified (preswitch BMI) analyses, only nonobese subgroups experienced increases in weight and BMI across all ART treatment groups (
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.
To understand the relationship between cardiovascular disease (CVD) risk and frailty among men (MWH) and women living with HIV (WWH), or at risk for HIV.
We considered 10-year coronary heart disease ...and atherosclerotic CVD risk by Framingham risk score (FRS, 2001 National Cholesterol Education Program Adult Treatment Program III) and Pooled Cohort Equations (PCE, 2013 American College of Cardiology/American Heart Association) in relation to the Fried Frailty Phenotype (FFP) in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS).
FFP was ascertained in MACS from 2004 to 2019 and in WIHS from 2005 to 2006 and 2011-2019. FFP score at least three of five components defined frailty. Repeated measures logistic regression (both cohorts) and Cox proportional hazards regression (MACS) were performed, controlled for education, income, cholesterol medication and hepatitis C virus serostatus, and among MWH and WWH, CD4+ cell count/μl, antiretroviral therapy, and HIV viral load.
There were 5554 participants (1265 HIV seronegative/1396 MWH; 768 seronegative/1924 WWH) included. Among men, high-risk FRS was associated with increased risk of incident frailty among seronegative adjusted hazard ratio (aHR)) = 2.12, 95% confidence interval (CI):1.22-3.69 and MWH (aHR = 2.19, 95% CI: 1.33-3.61). Similar associations were seen with high-risk PCE and incident frailty among SN (aHR = 1.88, 95% CI: 1.48-2.39) and MWH (aHR = 1.59, 95% CI: 1.26-2.00). Among women, high-risk PCE was associated with frailty in SN adjusted odds ratio (aOR) = 1.43, 95% CI: 1.02-2.00 and WWH (aOR = 1.36, 95% CI: 1.08-1.71); however, high-risk FRS was not (seronegative: aOR = 1.03, 95% CI: 0.30-3.49; WWH: aOR = 0.86, 95% CI: 0.23-3.20).
Higher CVD risk was associated with increased frailty regardless of HIV serostatus among men and women. These findings may inform clinical practices of screening for frailty.
To assess the association of race with clinical outcomes in HIV-positive women on continuous HAART.
Prospective study that enrolled women from 1994 to 1995 and 2001 to 2002.
Women's Interagency HIV ...Study, a community-based cohort in five US cities.
One thousand, four hundred and seventy-one HIV-positive continuous HAART users.
Times to AIDS and non-AIDS death and incident AIDS-defining illness (ADI) after HAART initiation.
In adjusted analyses, black vs. white women had higher rates of AIDS death adjusted hazard ratio (aHR) 2.14, 95% confidence interval (CI) 1.30, 3.50; P = 0.003 and incident ADI (aHR 1.58, 95% CI 1.08, 2.32; P = 0.02), but not non-AIDS death (aHR 0.91, 95% CI 0.59, 1.39; P = 0.65). Cumulative AIDS death incidence at 10 years was 17.3 and 8.3% for black and white women, respectively. Other significant independent pre-HAART predictors of AIDS death included peak viral load (aHR 1.70 per log₁₀, 95% CI 1.34, 2.16; P < 0.001), nadir CD4⁺ cell count (aHR 0.65 per 100 cells/μl, 95% CI 0.56, 0.76; P < 0.001), depressive symptoms by Center for Epidemiology Studies Depression score at least 16 (aHR 2.10, 95% CI 1.51, 2.92; P < 0.001), hepatitis C virus infection (aHR 1.57, 95% CI 1.02, 2.40; P = 0.04), and HIV acquisition via transfusion (aHR 2.33, 95% CI 1.21, 4.49; P = 0.01). In models with time-updated HAART adherence, association of race with AIDS death remained statistically significant (aHR 3.09, 95% CI 1.38, 6.93; P = 0.006).
In continuous HAART-using women, black women more rapidly died from AIDS or experienced incident ADI than their white counterparts after adjusting for confounders. Future studies examining behavioral and biologic factors in these women may further the understanding of HAART prognosis.
Background Rapid and accurate acute ischemic stroke (AIS) diagnosis is needed to expedite emergent thrombolytic and mechanical thrombectomy treatment. Changes in blood-based protein biomarkers during ...the first 24 h of AIS, the time window for treatment, could complement imaging techniques and facilitate rapid diagnosis and treatment. Methods We performed a systematic review according to PRISMA guidelines. MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched for eligible studies comparing levels of blood-based protein biomarkers in AIS patients with levels in healthy controls and stroke mimics. Protein biomarkers from the following pathophysiological categories were included: neurovascular inflammation (MMP-9, TNF-alpha), endothelial integrity (VCAM-1, ICAM-1), cell migration (E-Selectin, P-Selectin, L-Selectin), markers of glial and neuronal origin (GFAP, S100, S100B, NSE), and cardiac dysfunction (BNP, NT-proBNP). The literature search was limited to English-language publications before November 7th, 2023. Results A total of 61 studies from 20 different countries were identified, which included in total, 4,644 AIS patients, 2,242 stroke mimics, and 2,777 controls. Studies investigating TNF-alpha, MMP-9, VCAM-1, ICAM-1, E-Selectin, L-Selectin, GFAP, NSE, and S100B showed pronounced methodological heterogeneity, making between-study comparisons difficult. However, in 80% of NT-proBNP and BNP studies, and all P-selectin studies, higher biomarker levels were observed in AIS patients compared to healthy controls and/or patients with stroke mimics. Conclusion None of the biomarkers included showed sufficient evidence for additional diagnostic benefit for AIS. Comprehensive standardized global multicenter studies are needed to (1) permit comparability, (2) enable valid statements about protein-based biomarkers, and (3) reflect real-world scenarios.
As the use of Integrase inhibitor (INSTI)-class antiretroviral medications becomes more common to maintain long-term viral suppression, early reports suggest the potential for CNS side-effects when ...starting or switching to an INSTI-based regimen. In a population already at higher risk for developing mood and anxiety disorders, these drugs may have significant effects on PTSD scale symptom scores, particularly in women with HIV (WWH). A total of 551 participants were included after completing ≥ 1 WIHS study visits before and after starting/switching to an INSTI-based ART regimen. Of these, 14% were ART naïve, the remainder switched from primarily a protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. Using multivariable linear mixed effects models, we compared PTSD Civilian Checklist subscale scores before and after a “start/switch” to dolutegravir (DTG), raltegravir (RAL), or elvitegravir (EVG). Start/switch to EVG improved re-experiencing subscale symptoms (
P
’s < 0.05). Switching to EVG improved symptoms of avoidance (
P
= 0.01). Starting RAL improved arousal subscale symptoms (
P
= 0.03); however, switching to RAL worsened re-experiencing subscale symptoms (
P
< 0.005). Starting DTG worsened avoidance subscale symptoms (
P
= 0.03), whereas switching to DTG did not change subscale or overall PTSD symptoms (
P
’s > 0.08). In WWH, an EVG-based ART regimen is associated with improved PTSD symptoms, in both treatment naïve patients and those switching from other ART. While a RAL-based regimen was associated with better PTSD symptoms than in treatment naïve patients, switching onto a RAL-based regimen was associated with worse PTSD symptoms. DTG-based regimens either did not affect, or worsened symptoms, in both naïve and switch patients. Further studies are needed to determine mechanisms underlying differential effects of EVG, RAL and DTG on stress symptoms in WWH.
Frailty and falls occur commonly and prematurely in HIV-infected populations. Whether frailty in middle-age predicts future falls among HIV-infected women is unknown.
We evaluated associations of ...frailty with single and recurrent falls 10 years later among 729 HIV-infected and 326 uninfected women in the Women's Interagency HIV Study (WIHS) with frailty measured in 2005 and self-reported falls in 2014-2016. Frailty was defined as ≥3 of 5 Fried Frailty Index components: slow gait, reduced grip strength, exhaustion, unintentional weight loss and low physical activity. Stepwise logistic regression models determined odds of single (versus 0) or recurrent falls (≥2 versus 0) during the 2-year period; separate models evaluated frailty components.
HIV-infected women were older (median 42 versus 39 years; P<0.0001) and more often frail (14% versus 9%; P=0.04) than uninfected women. Over 2 years, 40% of HIV-infected versus 39% of uninfected women reported a fall (single fall in 15% HIV+ versus 18% HIV- women; recurrent falls in 25% HIV+ versus 20% HIV- women overall P=0.20). In multivariate models, frailty independently predicted recurrent falls (adjusted odds ratio aOR 1.84, 95% CI: 1.13, 2.97; P=0.01), but not a single fall. Among frailty components, unintentional weight loss independently predicted single fall (aOR 2.31, 95% CI: 1.28, 4.17; P=0.005); unintentional weight loss (aOR 2.26, 95% CI: 1.32, 3.86; P=0.003) and exhaustion (aOR 1.66, 95% CI: 1.10, 2.50; P=0.02) independently predicted recurrent falls.
Early frailty measurement among middle-aged women with or at-risk for HIV may be a useful tool to assess future fall risk.
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).
...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.
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).
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.
Objective
Physical activity is negatively associated with depressive symptoms. However, few studies consider dynamic associations of changes in physical activity and reciprocal relationships. This ...study aimed to perform comprehensive evaluations of relationships between physical activity and depression scores in women followed from mid‐ to late life.
Method
The Prospective Population Study of Women in Gothenburg, Sweden, provided repeated measures of self‐reported physical activity and depressive symptoms between 1974 and 2005 (baseline N = 676, 84.5% response rate). Depressive symptoms were assessed using the Montgomery–Åsberg Depression Rating Scale, and physical activity was evaluated by the Saltin–Grimby Physical Activity Level Scale. Latent growth curve analyses were used to evaluate associations of change, and cross‐lagged models were used to study the reciprocal relationship between physical activity and depression scores.
Results
At baseline, lower levels of physical activity were related to higher depression scores. Individuals with decreasing physical activity over time evidenced higher depression scores at 32‐year follow‐up. Higher average baseline depression score was related to declining levels of physical activity at subsequent examinations.
Conclusion
Reduced physical activity may be a long‐term consequence of depression. It is important to address individual changes in physical activity and not merely absolute levels of physical activity in relationship to depression.
Tau accumulation affecting white matter tracts is an early neuropathological feature of late-onset Alzheimer's disease (LOAD). There is a need to ascertain methods for the detection of early LOAD ...features to help with disease prevention efforts. The microstructure of these tracts and anatomical brain connectivity can be assessed by analyzing diffusion MRI (dMRI) data. Considering that family history increases the risk of developing LOAD, we explored the microstructure of white matter through dMRI in 23 cognitively normal adults who are offspring of patients with Late-Onset Alzheimer's Disease (O-LOAD) and 22 control subjects (CS) without family history of AD. We also evaluated the relation of white matter microstructure metrics with cortical thickness, volumetry, in vivo amyloid deposition (with the help of PiB positron emission tomography -PiB-PET) and regional brain metabolism (as FDG-PET) measures. Finally we studied the association between cognitive performance and white matter microstructure metrics. O-LOAD exhibited lower fiber density and fractional anisotropy in the posterior portion of the corpus callosum and right fornix when compared to CS. Among O-LOAD, reduced fiber density was associated with lower amyloid deposition in the right hippocampus, and greater cortical thickness in the left precuneus, while higher mean diffusivity was related with greater cortical thickness of the right superior temporal gyrus. Additionally, compromised white matter microstructure was associated with poorer semantic fluency. In conclusion, white matter microstructure metrics may reveal early differences in O-LOAD by virtue of parental history of the disorder, when compared to CS without a family history of LOAD. We demonstrate that these differences are associated with lower fiber density in the posterior portion of the corpus callosum and the right fornix.
•Healthy offspring of late-onset AD (O-LOAD) patients show decreased connectivity.•Gray matter anomalies are associated to altered white matter integrity among O-LOAD.•White matter dysconnectivity involves right fornix and splenium of corpus callosum.
The vaginal microbiota is known to impact women's health, but the biological factors that influence the composition of the microbiota are not fully understood. We previously observed that levels of ...glycogen in the lumen of the vagina were higher in women that had a high body mass index (BMI). Vaginal glycogen is thought to impact the composition of the vaginal microbiota. We therefore sought to determine if BMI was associated having or not having bacterial vaginosis (BV), as determined by the Amsel criteria. We also hypothesized that increased blood glucose levels could lead to the previously-observed higher vaginal glycogen levels and therefore investigated if hemoglobin A1c levels were associated with BV. We analyzed data from the Women's Interagency HIV Study using multiple multivariable (GEE) logistic regression models to assess the relationship between BMI, BV and blood glucose. Women with a BMI >30 kg/m2 (obese) had a lower rate (multivariable adjusted OR 0.87 (0.79-0.97), p = 0.009) of BV compared to the reference group (BMI 18.5-24.9 kg/m2). There was a significantly lower rate of BV in post-menopausal obese women compared to the post-menopausal reference group, but not in pre-menopausal women. HIV- post-menopausal obese women had a significantly lower rate of BV, but this was not seen in HIV+ post-menopausal obese women. Pre-menopausal women with a higher hemoglobin A1c (≥6.5%) had a significantly lower rate (multivariable adjusted OR 0.66 (0.49-0.91), p = 0.010) of BV compared to pre-menopausal women with normal hemoglobin A1c levels (<5.7%), but there was no difference in post-menopausal women. This study shows an inverse association of BMI with BV in post-menopausal women and hemoglobin A1c with BV in pre-menopausal women. Further studies are needed to confirm these relationships in other cohorts across different reproductive stages and to identify underlying mechanisms for these observed associations.
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