Publications by authors named "Deborah Gustafson"

166 Publications

Commentary on Lahiri et al. Weight and Body Mass Index Change After Switching to Integrase Inhibitors or Tenofovir Alafenamide Among Women Living with HIV.

J AIDS HIV Treat 2021 ;3(2):21-23

Department of Neurology, Section for NeuroEpidemiology, State University of New York Downstate Health Sciences University, Brooklyn, New York, USA.

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http://dx.doi.org/10.33696/AIDS.3.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291731PMC
January 2021

Menopause is associated with immune activation in women with HIV.

J Infect Dis 2021 Jun 26. Epub 2021 Jun 26.

Division of HIV, Infectious Diseases, and Global Medicine, University of California San Francisco, San Francisco, CA, USA.

Background: Persistent immune activation due to gut barrier dysfunction is a suspected cause of morbidity in HIV, but the impact of menopause on this pathway is unknown.

Methods: In 350 women with HIV from the Women's Interagency HIV Study, plasma biomarkers of gut barrier dysfunction (intestinal fatty acid binding protein; IFAB), innate immune activation (soluble CD14 and CD163; sCD14, sCD163), and systemic inflammation (interleukin-6 and tumor necrosis factor receptor 1; IL-6, TNFR1), were measured at 674 person-visits spanning ≤2 years.

Results: Menopause (post- vs. pre-menopausal status) was associated with higher plasma sCD14 and sCD163 in linear mixed-effects regression adjusting for age and other covariates (B [95% CI]=161.89ng/mL [18.37, 305.41] and 65.48 ng/mL [6.64, 124.33], respectively); but not with plasma IFAB, IL-6, or TNFR1. In piece-wise linear mixed-effects regression of biomarkers on years before/after the final menstrual period, sCD14 increased during the menopausal transition by 250.71 ng/mL per year (95% CI: 16.63, 484.79; p=0.04), but not in the pre-menopausal or post-menopausal periods.

Conclusions: In women with HIV, menopause may increase innate immune activation, but data did not support an influence on the gut barrier or inflammation. Clinical implications of immune activation during the menopausal transition warrants further investigation.
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http://dx.doi.org/10.1093/infdis/jiab341DOI Listing
June 2021

Urine Biomarkers of Kidney Tubule Health and Incident CKD Stage 3 in Women Living With HIV: A Repeated Measures Study.

Kidney Med 2021 May-Jun;3(3):395-404.e1. Epub 2021 Apr 17.

Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California, San Francisco, San Francisco, CA.

Rationale & Objective: Single measurements of urinary biomarkers reflecting kidney tubule health are associated with chronic kidney disease (CKD) risk in HIV infection, but the prognostic value of repeat measurements over time is unknown.

Study Design: Cohort study.

Setting & Participants: 647 women living with HIV infection enrolled in the Women's Interagency Health Study.

Exposures: 14 urinary biomarkers of kidney tubule health measured at 2 visits over a 3-year period.

Outcome: Incident CKD, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m at two 6-month visits and an average eGFR decline ≥ 3% per year.

Analytical Approach: We used multivariable generalized estimating equations adjusting for CKD risk factors to evaluate baseline, time-updated, and change-over-time biomarker associations with incident CKD. We compared CKD discrimination between models with and without a parsimoniously selected set of biomarkers.

Results: During a median 7 years of follow-up, 9.7% (63/647) developed CKD. In multivariable-adjusted analyses, 3 of 14 baseline biomarkers associated with incident CKD. In contrast, 10 of 14 time-updated biomarkers and 9 of 14 biomarkers modeled as change over time associated with incident CKD. Urinary epidermal growth factor (EGF), α-microglobulin (A1M), and albumin were selected using penalized regression methods. In the time-updated model, lower urinary EGF (risk ratio [RR] per 2-fold higher time-updated biomarker levels, 0.69; 95% CI, 0.58-0.81), higher urinary A1M (RR, 1.47; 95% CI, 1.25-1.73), and higher urinary albumin excretion (RR, 1.21; 95% CI, 1.03-1.42) were jointly associated with increased risk for CKD. Compared with a base model (C statistic, 0.75), CKD discrimination improved after adding urinary EGF, A1M, and albumin values across baseline (C = 0.81), time-updated (C = 0.83), and change-over-time (C = 0.83) models ( < 0.01 for all).

Limitations: Observational design, incident CKD definition limited to eGFR.

Conclusions: Repeat urinary biomarker measurements for kidney tubule health have stronger associations with incident CKD compared with baseline measurements and moderately improve CKD discrimination in women living with HIV infection.
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http://dx.doi.org/10.1016/j.xkme.2021.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178470PMC
April 2021

Food insecurity and frailty among women with and without HIV in the United States: a cross-sectional analysis.

J Int AIDS Soc 2021 Jun;24(6):e25751

Center for AIDS Prevention Studies, University of California, San Francisco (UCSF), San Francisco, CA, USA.

Introduction: Frailty is frequently observed among people with HIV, and food insecurity is associated with frailty in the general population. Evidence is scarce on the associations between food insecurity and frailty among women with HIV who may be particularly vulnerable to the impacts of food insecurity. The goal of this study was to assess associations between food insecurity and frailty among women with and without HIV.

Methods: There were 1265 participants from the Women's Interagency HIV Study who participated in frailty assessments in 2017. Frailty was measured using the Fried Frailty Phenotype, and women were subsequently categorized as robust, pre-frail or frail. Food insecurity was assessed using the U.S. Household Food Security Survey Module, with women categorized as having high, marginal, low or very low food security. Multinomial logistic regression models were conducted to examine cross-sectional associations between food insecurity and frailty while adjusting for socio-demographic, behavioural and HIV status covariates.

Results And Discussion: Approximately one-third (31.9%) of the women had marginal, low or very low food security, and the proportions of women who met the criteria for frailty or pre-frailty were 55.6% and 12.4% respectively. In the adjusted model, the relative risk ratio (RRR) of frailty for women with very low food security versus women with high food security was 3.37 (95% CI [1.38 to 8.24], p < 0.01); the corresponding RRR of pre-frailty was 3.63 (95% CI [1.76 to 7.51], p < 0.001). Higher annual household income was associated with lower RRRs of frailty or pre-frailty (p < 0.01). Similarly, older age was associated with more frequent frailty (RRR=1.06, 95% CI [1.03 to 1.09], p < 0.001). HIV serostatus was not significantly associated with either pre-frailty (RRR=0.97, 95% CI [0.71 to 1.31]) or frailty (RRR=0.75, 95% CI [0.48 to 1.16]).

Conclusions: Very low food security was associated with more frequent frailty and pre-frailty among women with and without for HIV. HIV serostatus was not associated with frailty.
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http://dx.doi.org/10.1002/jia2.25751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204023PMC
June 2021

Psychosocial Mechanisms of Self-rated Successful Aging with HIV: A Structural Equation Model.

AIDS Behav 2021 Jun 11. Epub 2021 Jun 11.

Emory University Nell Hodgson Woodruff School of Nursing, Atlanta, GA, USA.

This study tested a conceptual psychosocial model of self-rated successful aging (SRSA) with HIV. Our sample (n = 356) included older women living with HIV (OWLH): average age 56.5 years, 73% Black. SRSA was assessed using a research-based 10-point scale (higher scores = better outcomes). We conducted adjusted structural equation modeling. The global model included two latent variables-protective attributes (composite of positive psychosocial factors: resilience, personal mastery, optimism, spirituality) and psychological distress (composite of negative psychosocial factors: anxiety, depression, loneliness, internalized HIV-related stigma). The model showed good fit (χ(58) = 76, p = 0.06; RMSEA = 0.03; CFI = 0.99). Increased protective attributes were associated with improved SRSA both directly and mediated by improved coping with stress. While psychological distress did not have a direct effect on SRSA, it was indirectly associated with worsened SRSA via diminished protective attributes and via decreased coping with stress. Findings suggest the need for interventions enhancing positive and mitigating negative psychosocial factors in OWLH.
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http://dx.doi.org/10.1007/s10461-021-03340-7DOI Listing
June 2021

Dietary intake is associated with neuropsychological impairment in women with HIV.

Am J Clin Nutr 2021 Jul;114(1):378-389

Department of Medicine, Division of HIV, Infectious Diseases, and Global Medicine, University of California San Francisco, San Francisco, CA, USA.

Background: Diet is a modifiable risk factor that may influence cognition in people with HIV.

Objectives: We examined the association between dietary intake and cognition in women with HIV (WWH) and HIV-seronegative women.

Methods: An 18-item dietary National Cancer Institute screener was completed by 729 WWH and 346 HIV-seronegative Women's Interagency HIV Study participants. Daily intake frequencies of processed meats, sweet beverages, fish, whole milk, and vegetables were calculated. Participants completed biennial neuropsychological (NP) testing. NP domains included attention/working memory, executive function, processing speed, memory, learning, fluency, and motor function. NP impairment was defined as demographically adjusted T-scores (mean = 50; SD = 10) ≤40 at ≥1 visit after completing the dietary screener. Multivariable logistic regression, stratified by HIV serostatus, examined associations between intake frequency tertile (referent = lowest intake) and NP performance.

Results: Dietary intake frequencies of individual food line items were similar between WWH and HIV-seronegative women, except for sweet beverages, for which HIV-seronegative women reported higher intake frequencies than WWH (P values < 0.05). In WWH, multivariable-adjusted models indicated higher odds of NP impairment with higher intake frequencies of processed meat [P = 0.006; ORupper tertile = 1.91 (95% CI: 1.23-2.95; P = 0.003); ORmiddle tertile = 1.66 (95% CI: 1.14-2.42; P = 0.01)], sweet beverages [P = 0.02; ORupper tertile = 1.75 (95% CI: 1.17-2.64; P = 0.007)], fish [P = 0.01; ORupper tertile = 1.70 (95% CI: 1.10-2.64; P = 0.02)], and whole milk [P = 0.029; ORupper tertile = 1.66 (95% CI: 1.14-2.42; P = 0.008)]. Lower odds of NP impairment [P = 0.005; ORupper tertile = 0.65 (95% CI: 0.45-0.95; P = 0.02); ORmiddle tertile = 0.42 (95% CI: 0.24-0.73; P = 0.002)] were associated with higher vegetable intakes. In HIV-seronegative women, multivariable-adjusted models did not show associations between food line items/diet quality score and NP outcomes.

Conclusions: Intakes of processed meat, sweet beverages, whole milk, fish, and vegetables may be associated with NP functions among WWH. Associations among WWH are not directly comparable to those among HIV-seronegative women, because models were conducted on each group separately given controls for HIV-specific covariates in WWH. Further studies are needed using more rigorous dietary assessment methods and lengthier longitudinal follow-ups.
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http://dx.doi.org/10.1093/ajcn/nqab038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246600PMC
July 2021

Obesity is associated with lower bacterial vaginosis prevalence in menopausal but not pre-menopausal women in a retrospective analysis of the Women's Interagency HIV Study.

PLoS One 2021 8;16(3):e0248136. Epub 2021 Mar 8.

Hektoen Institute of Medicine, Chicago, IL, United States of America.

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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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248136PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939367PMC
March 2021

Patterns and Predictors of Cognitive Function Among Virally Suppressed Women With HIV.

Front Neurol 2021 11;12:604984. Epub 2021 Feb 11.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Cognitive impairment remains frequent and heterogeneous in presentation and severity among virally suppressed (VS) women with HIV (WWH). We identified cognitive profiles among 929 VS-WWH and 717 HIV-uninfected women from 11 Women's Interagency HIV Study sites at their first neuropsychological (NP) test battery completion comprised of: Hopkins Verbal Learning Test-Revised, Trail Making, Symbol Digit Modalities, Grooved Pegboard, Stroop, Letter/Animal Fluency, and Letter-Number Sequencing. Using 17 NP performance metrics (T-scores), we used Kohonen self-organizing maps to identify patterns of high-dimensional data by mapping participants to similar nodes based on T-scores and clustering those nodes. Among VS-WWH, nine clusters were identified (entropy = 0.990) with four having average T-scores ≥45 for all metrics and thus combined into an "unimpaired" profile ( = 311). Impaired profiles consisted of weaknesses in: (1) sequencing (; = 129), (2) speed (; = 144), (3) learning + recognition (; = 137), (4) learning + memory (; = 86), and (5) learning + processing speed + attention + executive function (; = 122). Sociodemographic, behavioral, and clinical variables differentiated profile membership using Random Forest models. The top 10 variables distinguishing the combined impaired vs. unimpaired profiles were: clinic site, age, education, race, illicit substance use, current and nadir CD4 count, duration of effective antiretrovirals, and protease inhibitor use. Additional variables differentiating each impaired from unimpaired profile included: depression, stress-symptoms, income (); depression, employment (); depression, integrase inhibitor (INSTI) use (); employment, INSTI use, income, atazanavir use, non-ART medications with anticholinergic properties (); and marijuana use (). Findings highlight consideration of NP profile heterogeneity and potential modifiable factors contributing to impaired profiles.
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http://dx.doi.org/10.3389/fneur.2021.604984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928382PMC
February 2021

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

J Acquir Immune Defic Syndr 2021 06;87(2):842-850

Department of Medicine, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY.

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.
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http://dx.doi.org/10.1097/QAI.0000000000002651DOI Listing
June 2021

Cognitive changes during the menopausal transition: a longitudinal study in women with and without HIV.

Menopause 2021 01 11;28(4):360-368. Epub 2021 Jan 11.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Objective: To assess longitudinal changes in cognitive performance across menopause stages in a sample comprised primarily of low-income women of color, including women with HIV (WWH).

Methods: A total of 443 women (291 WWH; 69% African American; 18% Hispanic; median age = 42 y) from the Women's Interagency HIV Study completed tests of verbal learning and memory, attention/working memory, processing speed, verbal fluency, motor skills, and executive function first at an index premenopausal visit and thereafter once every 2 years for up to six visits (mean follow-up = 5.7 y). General linear-mixed effects regression models were run to estimate associations between menopause stages and cognition, in the overall sample and in WWH. We examined both continuous scores and categorical scores of cognitive impairment (yes/no >1 standard deviation below the mean).

Results: Adjusting for age and relevant covariates, the overall sample and WWH showed longitudinal declines in continuous measures of learning, memory, and attention/working memory domains from the premenopause to the early perimenopause and from the premenopause to the postmenopause, Ps < 0.05 to < 0.001. Effects on those same domains were also evident in categorical scores of cognitive impairment, with the increased odds of impairment ranging from 41% to 215%, Ps < 0.05 to < 0.001. The increase in predicted probability of impairment by menopausal stage (% affected) ranged from 4% to 13%.

Conclusions: Menopause stage was a key determinant of cognition in a sample of low-income women of color, including WWH. Many of these changes reached a clinically significant level of cognitive impairment.
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http://dx.doi.org/10.1097/GME.0000000000001725DOI Listing
January 2021

Menopausal status and observed differences in the gut microbiome in women with and without HIV infection.

Menopause 2021 01 11;28(5):491-501. Epub 2021 Jan 11.

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.

Objective: Gut microbiota respond to host physiological phenomena, yet little is known regarding shifts in the gut microbiome due to menopausal hormonal and metabolic changes in women. HIV infection impacts menopause and may also cause gut dysbiosis. We therefore sought to determine the association between menopausal status and gut microbiome composition in women with and without HIV.

Methods: Gut microbiome composition was assessed in stool from 432 women (99 premenopausal HIV+, 71 premenopausal HIV-, 182 postmenopausal HIV+, 80 postmenopausal HIV-) via 16S rRNA gene sequencing. We examined cross-sectional associations of menopause with gut microbiota overall diversity and composition, and taxon and inferred metagenomic pathway abundance. Models were stratified by HIV serostatus and adjusted for age, HIV-related variables, and other potential confounders.

Results: Menopause, ie post- versus premenopausal status, was associated with overall microbial composition only in women with HIV (permutational MANOVA of Jensen Shannon Divergence: P = 0.01). In women with HIV, menopause was associated with enrichment of gram-negative order Enterobacteriales, depletion of highly abundant taxa within Prevotella copri, and alterations in other low-abundance taxa. Additionally, menopause in women with HIV was associated with enrichment of metagenomic pathways related to Enterobacteriales, including degradation of amino acids and phenolic compounds, biosynthesis of enterobactin, and energy metabolism pathways. Menopause-related differences in some low-abundance taxa were also observed in women without HIV.

Conclusions: A changing gut microbiome may be an overlooked phenomenon of reproductive aging in women with HIV. Longitudinal assessments across all reproductive stages are necessary to confirm these findings and identify health implications.
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http://dx.doi.org/10.1097/GME.0000000000001730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068580PMC
January 2021

Plasma Lipidomic Profiles and Risk of Diabetes: 2 Prospective Cohorts of HIV-Infected and HIV-Uninfected Individuals.

J Clin Endocrinol Metab 2021 Mar;106(4):999-1010

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.

Objectives: Antiretroviral therapy (ART) use is associated with disrupted lipid and glucose metabolism in people with HIV infection. We aimed to identify plasma lipid species associated with risk of diabetes in the context of HIV infection.

Research Design And Methods: We profiled 211 plasma lipid species in 491 HIV-infected and 203 HIV-uninfected participants aged 35 to 55 years from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Cox proportional hazards model was used to examine associations between baseline lipid species and incident diabetes (166 diabetes cases were identified during a median follow-up of 12.6 years).

Results: We identified 11 lipid species, representing independent signals for 8 lipid classes/subclasses, associated with risk of diabetes (P < 0.05 after FDR correction). After adjustment for multiple covariates, cholesteryl ester (CE) (22:4), lysophosphatidylcholine (LPC) (18:2), phosphatidylcholine (PC) (36:4), phosphatidylcholine plasmalogen (34:3), and phosphatidylethanolamine (PE) (38:2) were associated with decreased risk of diabetes (HRs = 0.70 to 0.82 per SD increment), while diacylglycerol (32:0), LPC (14:0), PC (38:3), PE (36:1), and triacylglycerol (50:1) were associated with increased risk of diabetes (HRs = 1.26 to 1.56 per SD increment). HIV serostatus did not modify any lipid-diabetes associations; however, most of these lipid species were positively associated with HIV and/or ART use, including 3 diabetes-decreased ( CE [22:4], LPC [18:2], PE [38:2]) and all 5 diabetes-increased lipid species.

Conclusions: This study identified multiple plasma lipid species associated with incident diabetes. Regardless of the directions of their associations with diabetes, most diabetes-associated lipid species were elevated in ART-treated people with HIV infection. This suggests a complex role of lipids in the link between ART and diabetes in HIV infection.
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http://dx.doi.org/10.1210/clinem/dgab011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993589PMC
March 2021

Integrase Strand Transfer Inhibitor Start or Switch Impacts Learning in Women With HIV.

J Acquir Immune Defic Syndr 2021 04;86(5):593-599

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.

Background: Integrase strand transfer inhibitors (INSTIs) are first-line regimens for HIV treatment. We aimed to examine their impact on cognitive performance and depressive symptoms in women with HIV (WWH).

Setting: Women's Interagency HIV Study, a multisite, prospective, cohort study.

Methods: WWH who started or switched to INSTI-based antiretroviral therapy (ART) and completed neuropsychological testing and the Center for Epidemiological Studies-Depression (CES-D) scale before and after INSTI start/switch were included in the analyses. Primary outcomes were demographically corrected cognitive domain T-scores. Linear mixed-effects models adjusted for relevant covariates were used to examine effects of start/switch of any INSTI and individual INSTI drugs on cognition and CES-D scores.

Results: Six hundred thirty-nine WWH, median age 49 (interquartile range 12) years, 66% Black non-Hispanic, had neuropsychological and CES-D scale data before and after INSTI start/switch. Although 14% started INSTI-based ART, the remainder switched to INSTI-based ART from another regimen. Overall, any INSTI use was associated with poorer learning post-INSTI. Specifically, use of dolutegravir and elvitegravir, but not raltegravir, was associated with poorer learning. In analyses restricted to INSTI switch, any INSTI use, and dolutegravir use, was associated with poorer learning. Among those switching from a PI-based regimen, INSTIs overall and dolutegravir remained associated with poorer learning; switching from a nonnucleoside reverse transcriptase inhibitor to dolutegravir was also associated with poorer learning. INSTI start/switch was not related to depressive symptom changes.

Conclusions: INSTI use was associated with poorer learning among WWH. These changes were mainly observed in elvitegravir and dolutegravir users, indicating that the impact of INSTI on cognition in WWH may not be a class effect.
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http://dx.doi.org/10.1097/QAI.0000000000002608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319920PMC
April 2021

Weight and Body Mass Index Change After Switching to Integrase Inhibitors or Tenofovir Alafenamide Among Women Living with HIV.

AIDS Res Hum Retroviruses 2021 06 12;37(6):461-467. Epub 2021 Jan 12.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

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.
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http://dx.doi.org/10.1089/AID.2020.0197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213005PMC
June 2021

COVID-19 symptoms and SARS-CoV-2 infection among people living with HIV in the US: the MACS/WIHS combined cohort study.

HIV Res Clin Pract 2020 10 19;21(5):130-139. Epub 2020 Nov 19.

Department of Medicine, UNC School Division of Medicine, The Infectious Diseases, University of North Carolina School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Background: SARS-CoV-2 infection among People Living With HIV (PLWH) is not well-described.

Objective: To study COVID-19 symptoms and SARS-CoV-2 PCR-based swab testing among participants of the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS).

Methods: A telephone survey was collected April-June 30, 2020. Symptom and testing prevalence were explored. Multivariable logistic regression was used to examine the factors associated with SARS-CoV-2 positivity.

Results: The survey was completed by 3411 participants, including 2078 (61%) PLWH and 1333 HIV-seronegative (SN) participants from across the US. Thirteen percent (n = 441) were tested for SARS-CoV-2 infection (13.4% of PLWH vs 12.2% of SN). Among those tested, positivity was higher in PLWH than SN (11.2% vs 6.1%,  = 0.08). Reasons for not being tested included testing not being available (30% of participants) and not knowing where to get tested (16% of participants). Most symptoms reported since January 2020 were similar in PLWH and SN, including headache (23% vs. 24%), myalgias (19% vs 18%), shortness of breath (14% vs 13%), chills (12% vs 10%), fever (6% vs 6%) and loss of taste or smell (6% vs 7%). Among PLWH who tested positive for SARS-CoV-2 DNA, the most common symptoms were headache (71%), myalgia (68%), cough (68%) and chills (65%). In multivariable analysis among those tested, the odds of SARS-CoV-2 positivity were higher among PLWH than SN (aOR = 2.22 95%CI = 01.01-4.85,  = 0.046) and among those living with others versus living alone (aOR = 2.95 95%CI = 1.18-7.40).

Conclusion: Prevalence and type of COVID-19 symptoms were similar in PLWH and SN. SARS-CoV-2 infection may be elevated among PLWH.
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http://dx.doi.org/10.1080/25787489.2020.1844521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682380PMC
October 2020

Factors Predicting Detrimental Change in Declarative Memory Among Women With HIV: A Study of Heterogeneity in Cognition.

Front Psychol 2020 15;11:548521. Epub 2020 Oct 15.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Objective: Statistical techniques used to study cognitive function in HIV typically yield normative estimates and can mask the heterogeneity in cognitive trajectories over time. We applied a novel statistical approach to identify clusters of individuals with distinct patterns of change in declarative memory in HIV-seropositive (HIV+) and HIV-seronegative (HIV-) women.

Methods: 1731 women from the Women's Interagency HIV Study, a multi-center, prospective cohort study, completed the Hopkins Verbal Learning Test-Revised (HLVT-R) at >2 visits. To derive subgroups with similar patterns of decline by HIV-serostatus, we used a mixed-effects framework that modeled the trajectory of multiple declarative memory outcomes over time, while simultaneously clustering individuals.

Results: Of the 1731 participants, 1149 were HIV+ (70% Black/African American [AA]; 30% White/Other [W/O]) and 582 were HIV- (68% AA; 32% W/O). Race stratification was necessary to optimize clustering. Among HIV+AA's, four subgroups emerged: a subgroup with minimal decline, two with accelerated decline, and one with stable but low performance. In HIV- AA, three subgroups emerged: one with minimal decline and two with accelerated decline. In multivariable-adjusted models among HIV+, individuals with accelerated decline were less educated ( < 0.001) and more likely to have a history of depression ( < 0.001) versus those with minimal decline. Similar subgroups were identified in W/O HIV+ and W/O HIV- participants.

Conclusion: We identified clinically meaningful subgroups of women with distinct phenotypes of declarative memory decline, which depend on race and HIV-serostatus using a data driven approach. Identification of underlying mechanisms and risk factors contributing to the observed differences are warranted. More broadly our modeling approach could be other populations to identify risk factors for accelerated cognitive decline and to personalize interventions.
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http://dx.doi.org/10.3389/fpsyg.2020.548521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594511PMC
October 2020

Metabolic Changes Associated With the Use of Integrase Strand Transfer Inhibitors Among Virally Controlled Women.

J Acquir Immune Defic Syndr 2020 11;85(3):355-362

Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA.

Background: Integrase strand transfer inhibitors (INSTIs) have been associated with weight gain among women living with HIV. We aimed to investigate the association between INSTIs and change in cardiometabolic risk indicators.

Setting: Retrospective cohort.

Methods: Data from 2006 to 2017 were analyzed from women living with HIV enrolled in the longitudinal Women's Interagency HIV Study who were virally controlled on antiretroviral therapy (ART) for ≥5 consecutive semiannual visits. Women who switched/added an INSTI to ART (INSTI group) were compared with women who remained on non-INSTI ART (non-INSTI group). Outcomes included changes in fasting lipids and glucose, hemoglobin A1c (HbA1c), blood pressure (BP), and incident diabetes, hypertension, and insulin resistance. Outcomes were measured 6-12 months before and 6-18 months after INSTI switch/add in the INSTI group with comparable visits in the non-INSTI group. Longitudinal linear regression models compared change over time in each outcome by the study group.

Results: One thousand one hundred eighteen participants (234 INSTI, 884 non-INSTI) were followed for a median 2.0 (Q1 1.9, Q3 2.0) years. Participants were median age 49 years, 61% Black, and 73% overweight or obese (body mass index ≥25 kg/m). Compared with non-INSTI, the INSTI group experienced greater increases in HbA1c (+0.05 vs. -0.06 mg/dL, P = 0.0318), systolic BP (+3.84 vs. +0.84 mm Hg, P = 0.0191), and diastolic BP (+1.62 vs. -0.14 mm Hg, P = 0.0121), with greatest change in HbA1c among women on INSTIs with ≥5% weight gain.

Conclusions: INSTI use was associated with unfavorable changes in HbA1c and systolic and diastolic BP during short-term follow-up. Further research is needed to understand long-term cardiometabolic effects of INSTI use.
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http://dx.doi.org/10.1097/QAI.0000000000002447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577246PMC
November 2020

Women's HIV disclosure to the dentist: Does frequent contact matter?

J Public Health Dent 2021 12 13;81(1):65-76. Epub 2020 Oct 13.

School of General Studies and Mailman School of Public Health, Department of Sociomedical Sciences, Columbia University, New York, NY, USA.

Objectives: Research has shown inconsistent patterns of patients' HIV serostatus disclosure to their dentists. Common barriers to disclosure have included confidentiality concerns, fear of treatment refusal, and discrimination. This study evaluated the prevalence of HIV serostatus disclosure to the dentist, whether the frequency of dental care utilization is associated with disclosure, and reasons for nondisclosure among women living with HIV.

Methods: We administered a cross-sectional oral health survey to 1,526 women living with HIV in the Women's Interagency HIV Study including questions regarding HIV serostatus disclosure to dentists. Logistic regression models were used to analyze the association between dental care utilization (at least annually versus less than annually) and HIV serostatus disclosure to dentists.

Results: Overall, 83 percent of women reported that they disclosed their HIV serostatus to their dentist. The most common reasons for nondisclosure were: a) the dentist did not ask, b) believing that the dentist did not need to know, and c) not having a consistent dentist. In the multivariable logistic regression model, at least annual dental care utilization, compared to less than annual, led to a 59 percent reduction in the odds of HIV nondisclosure to the dentist.

Discussion: Study findings highlight that dentists who see their patients infrequently should consider methods for overcoming barriers to HIV nondisclosure and the possibility that their patient's HIV serostatus is undisclosed. Educating women living with HIV about how disclosure to dentists is a critical component of their dental assessment and treatment, and how preventive dental treatment can improve overall health outcomes, is important.
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http://dx.doi.org/10.1111/jphd.12403DOI Listing
December 2021

Dietary fatty acids and risk of Alzheimer's disease and related dementias: Observations from the Washington Heights-Hamilton Heights-Inwood Columbia Aging Project (WHICAP).

Alzheimers Dement 2020 12 27;16(12):1638-1649. Epub 2020 Jul 27.

Department of Neurology, The Gertrude H. Sergievsky Center, Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University and The New York Presbyterian Hospital, New York, New York, USA.

Introduction: High dietary intake of long chain, polyunsaturated fatty acids is associated with lower Alzheimer's disease (AD) risk.

Methods: Washington Heights-Hamilton Heights-Inwood Columbia Aging Project is a multiethnic, prospective observational study of aging and dementia among elderly (≥ 65 years). Dietary intake was measured using a food frequency questionnaire. Dietary short-, medium-, and long-chain fatty acid intakes were categorized by number of carbons and double bonds. Consensus AD diagnoses were made. Associations between AD risk and dietary fatty acid and cholesterol intakes were estimated using multivariable Cox proportional hazards regression models.

Results: Of 2612 multiethnic women (67%) and men (baseline age 76.3 [6.4] years), 380 developed AD over an average 4.5 years follow-up. Lower risk of AD was associated with increasing intakes of docosahexaenoic acid (DHA; hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.57 to 0.95, P = 0.018) and eicosapentaenoic acid (EPA; HR = 0.74, 95% CI: 0.57 to 0.95, P = 0.021), and longer AD-free survival (P < 0.05).

Discussion: Higher intake of DHA and EPA are protective for AD.
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http://dx.doi.org/10.1002/alz.12154DOI Listing
December 2020

Starting or Switching to an Integrase Inhibitor-Based Regimen Affects PTSD Symptoms in Women with HIV.

AIDS Behav 2021 Jan;25(1):225-236

Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street/ Meyer 6-113, Baltimore, MD, 21287-7613, USA.

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.
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http://dx.doi.org/10.1007/s10461-020-02967-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948485PMC
January 2021

Oral health-related quality of life and unmet dental needs among women living with HIV.

J Am Dent Assoc 2020 07;151(7):527-535

Background: Oral health-related quality of life (OHRQoL) is a multidimensional, perception-based measure of how oral health affects social and physical functioning and self-image. OHRQoL is important for assessing women living with HIV (WLWH) who may have unmet dental needs and experience disparities that impact dental care accessibility.

Methods: In 2016, the authors conducted an assessment of OHRQoL among a national sample of 1,526 WLWH in the Women's Interagency HIV Study using the Oral Health Impact Profile instrument, which assesses the frequency of 14 oral health impact items. OHRQoL was measured using multivariable linear regression with a negative binomial distribution to assess the association between report of a recent unmet dental need and OHRQoL.

Results: "Fair or poor" oral health condition was reported by 37.8% (n = 576) of WLWH. Multivariable linear regression showed that unmet dental needs had the strongest positive association with poor OHRQoL (difference in Oral Health Impact Profile mean, 2.675; P < .001) compared with not having unmet needs. The frequency of dental care utilization was not associated with higher OHRQoL. Older age, fair or poor dental condition, smoking, symptoms of anxiety and loneliness, and poor OHRQoL were also associated with worse OHRQoL.

Conclusion: Self-perceived impact of oral health on social and physical function and self-image, as measured by OHRQoL, may be an easily assessable but underrecognized aspect of OHRQoL, particularly among women aging with HIV.

Practical Implications: Dentists should implement OHRQoL assessments in their management of the care of patients with HIV to identify those who do have significant oral health impacts.
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http://dx.doi.org/10.1016/j.adaj.2020.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337358PMC
July 2020

Early Inflammatory Signatures Predict Subsequent Cognition in Long-Term Virally Suppressed Women With HIV.

Front Integr Neurosci 2020 24;14:20. Epub 2020 Apr 24.

Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, United States.

Immunologic function is an important determinant of cognition. Here we examined the contribution of early immune signatures to cognitive performance among HIV-infected, virally suppressed women (HIV+VS) and in HIV-uninfected (HIV-) women. Specifically, we measured serum inflammatory markers, developed combinatory immune signatures, and evaluated their associations with cognition. Forty-nine HIV+VS women in the Women's Interagency HIV Study (WIHS) who achieved viral suppression shortly after effective antiretroviral therapy (ART) initiation, and 56 matched HIV- women were selected. Forty-two serum inflammatory markers were measured within 2 years of effective ART initiation for HIV+VS women, and at an initial timepoint for HIV- women. The same inflammatory markers were also measured approximately 1, 7, and 12 years later for all women. Of the 105 women with complete immune data, 83 (34 HIV+VS, 49 HIV-) also had cognitive data available 12 years later at ≥1 time points (median = 3.1). We searched for combinatory immune signatures by adapting a dynamic matrix factorization analytic method that builds upon Tucker decomposition followed by Ingenuity Pathway Analysis to facilitate data interpretation. Seven combinatory immune signatures emerged based on the Frobenius residual. Three signatures were common between HIV+VS and HIV- women, while four signatures were unique. These inflammatory signatures predicted subsequent cognitive performance in both groups using mixed-effects modeling, but more domain-specific associations were significant in HIV+VS than HIV- women. Leukocyte influx into brain was a major contributor to cognitive function in HIV+VS women, while T cell exhaustion, inflammatory response indicative of depressive/psychiatric disorders, microglial activity, and cytokine signaling predicted both global and domain-specific performance for HIV- women. Our findings suggest that immune signatures may be useful diagnostic, prognostic, and immunotherapeutic targets predictive of subsequent cognitive performance. Importantly, they also provide insight into common and distinct inflammatory mechanisms underlying cognition in HIV- and HIV+VS women.
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http://dx.doi.org/10.3389/fnint.2020.00020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193823PMC
April 2020

Associations between Antiretrovirals and Cognitive Function in Women with HIV.

J Neuroimmune Pharmacol 2021 03 24;16(1):195-206. Epub 2020 Mar 24.

Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Cognitive complications persist in antiretroviral therapy(ART)-treated people with HIV. However, the pattern and severity of domain-specific cognitive performance is variable and may be exacerbated by ART-mediated neurotoxicity. 929 women with HIV(WWH) from the Women's Interagency HIV Study who were classified into subgroups based on sociodemographic and longitudinal behavioral and clinical data using semi-parametric latent class trajectory modelling. Five subgroups were comprised of: 1) well-controlled HIV with vascular comorbidities(n = 116); 2) profound HIV legacy effects(CD4 nadir <250 cells/μL; n = 275); 3) primarily <45 year olds with hepatitis C(n = 165); 4) primarily 35-55 year olds(n = 244), and 5) poorly-controlled HIV/substance use(n = 129). Within each subgroup, we fitted a constrained continuation ratio model via penalized maximum likelihood to examine adjusted associations between recent ART agents and cognition. Most drugs were not associated with cognition. However, among the few drugs, non-nucleoside reverse transcriptase inhibitor (NNRTIs) and protease inhibitors(PIs) were most commonly associated with cognition, followed by nucleoside reverse transcriptase inhibitors(NRTIs) and integrase inhibitors(IIs). Directionality of ART-cognition associations varied by subgroup. Better psychomotor speed and fluency were associated with ART for women with well-controlled HIV with vascular comorbidities. This pattern contrasts women with profound HIV legacy effects for whom poorer executive function and fluency were associated with ART. Motor function was associated with ART for younger WWH and primarily 35-55 year olds. Memory was associated with ART only for women with poorly-controlled HIV/substance abuse. Findings demonstrate interindividual variability in ART-cognition associations among WWH and highlight the importance of considering sociodemographic, clinical, and behavioral factors as an underlying contributors to cognition. Are antiretroviral agents a risk factor for cognitive complications in women with HIV? We examind associations between ART-agents and cognitive function among similar subgroups of women with HIV from the Women's Interagency HIV study. The patterns of associations depended on sociodemographic, clinical, and behavioral characteristics of women.
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http://dx.doi.org/10.1007/s11481-020-09910-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511435PMC
March 2021

Psychosocial Resources and Emotions in Women Living With HIV Who Have Cognitive Impairment: Applying the Socio-Emotional Adaptation Theory.

Res Theory Nurs Pract 2020 01;34(1):49-64

Emory University School of Medicine, Division of Infectious Disease, Atlanta, GA.

Decreased cognitive function is related to undesirable psychological outcomes such as greater emotional distress and lower quality of life, particularly among women living with HIV who experience cognitive impairment (WLWH-CI). Yet, few studies have examined the psychosocial resources that may attenuate these negative emotional outcomes. The current study sought to identify the interrelated contributions of social relationships and psychological resources in 399 WLWH-CI by applying Socio-Emotional Adaptation (SEA) theory using data from the Women's Interagency HIV Study (WIHS). Cognitive impairment (CI) was defined as impairment on two or more cognitive domains. Logistic regression models were used to estimate the odds of experiencing specific emotions due to a combination of four psychosocial resources. Emotions (i.e., depression, apathy, fear, anger, and acceptance) were related to a combination of binary (positive/negative) psychosocial resources including relationship with an informal support partner, relationship with a formal caregiver, coping, and perceived control. Understanding the conditions that may influence emotions in WLWH-CI is important for identifying and appropriately addressing the needs of this population. As CI increases, these individuals experience increasing challenges with articulating their care needs and having their needs met. As such, it becomes increasingly important to identify possible triggers for emotional responses to best address these underlying challenges.
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http://dx.doi.org/10.1891/1541-6577.34.1.49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062986PMC
January 2020

Associations between Antiretroviral Drugs on Depressive Symptomatology in Homogenous Subgroups of Women with HIV.

J Neuroimmune Pharmacol 2021 03 13;16(1):181-194. Epub 2020 Jan 13.

Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street/ Meyer 6-113, Baltimore, MD, 21287-7613, USA.

Antiretroviral therapy (ART) is inconsistently associated with depression. These associations may depend on factors such as biological sex, age, and health status. Identifying such factors may help optimize treatment of HIV and depression. We implemented a novel approach to examine interindividual variability in the association between ART agents and depressive symptoms. 3434 women living with HIV (WLWH) from the Women's Interagency HIV Study (WIHS) were computationally divided into subgroups based on sociodemographic (e.g., age) and longitudinal (from 1995 to 2016) behavioral and clinical profiles (e.g., substance use, HIV RNA, CD4 counts). Five subgroups (n's ranged from 482 to 802) were identified and characterized as those with: controlled HIV/vascular comorbidities; profound HIV legacy effects; younger women [<45 years of age] with hepatitis C; primarily 35-55 year olds; and poorly controlled HIV/substance use. Within each subgroup, we examined associations between ART agents used over the past 6 months and item-level depressive symptoms on the Center for Epidemiologic Studies Depression Scale. Tenofovir (4 of 5 subgroups) followed by efavirenz, emtricitabine, stavudine, lopinavir, etravirine, nelfinavir, ritonavir, and maraviroc were the most common agents associated with depressive symptoms, although the pattern and directionality varied by subgroup. For example, lopinavir was associated with fewer symptoms among the subgroup with a legacy HIV effect but more symptoms among the subgroup with well-controlled HIV/vascular comorbidities. Unexpectedly, dolutegravir and raltegravir were not associated with depressive symptoms among any subgroup. Findings underscore marked interindividual variability in ART agents on depression in WLWH. Sociodemographic, clinical, and behavioral factors are important determinants of the relationship between ART agents and depressive symptoms in WLWH. Graphical Abstract Are antiretroviral agents a risk factor for depressive symptoms in women with HIV? We examined associations between ART-agents and depressive symptoms among similar subgroups of women with HIV from the Women's Interagency HIV Study. The patterns of associations depended on sociodemographic, clinical, and behavioral characteristics of women.
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http://dx.doi.org/10.1007/s11481-019-09899-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430262PMC
March 2021

White matter fiber density abnormalities in cognitively normal adults at risk for late-onset Alzheimer's disease.

J Psychiatr Res 2020 03 3;122:79-87. Epub 2020 Jan 3.

Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta, Instituto de Neurociencias FLENI-CONICET, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Departamento de Física, Facultad de Cs. Exactas y Naturales, Universidad de Buenos Aires, Argentina.

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.
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http://dx.doi.org/10.1016/j.jpsychires.2019.12.019DOI Listing
March 2020

African Mitochondrial DNA Haplogroup L2 Is Associated With Slower Decline of β-cell Function and Lower Incidence of Diabetes Mellitus in Non-Hispanic, Black Women Living With Human Immunodeficiency Virus.

Clin Infect Dis 2020 11;71(8):e218-e225

Tennessee Valley Healthcare System-Veterans Affairs Hospital, Nashville, Tennessee, USA.

Background: Susceptibility to metabolic diseases may be influenced by mitochondrial genetic variability among people living with human immunodeficiency virus (HIV; PLWH), but remains unexplored in populations with African ancestry. We investigated the association between mitochondrial DNA (mtDNA) haplogroups and the homeostatic model assessments of β-cell function (HOMA-B) and insulin resistance (HOMA-IR), as well as incident diabetes mellitus (DM), among Black women living with or at risk for HIV.

Methods: Women without DM who had fasting glucose (FG) and insulin (FI) data for ≥2 visits were included. Haplogroups were inferred from genotyping data using HaploGrep. HOMA-B and HOMA-IR were calculated using FG and FI data. Incident DM was defined by a combination of FG ≥ 126 mg/dL, the use of DM medication, a DM diagnosis, or hemoglobin A1c ≥ 6.5%. We compared HOMA-B, HOMA-IR, and incident DM by haplogroups and assessed the associations between HOMA-B and HOMA-IR and DM by haplogroup.

Results: Of 1288 women (933 living with HIV and 355 living without HIV), PLWH had higher initial HOMA-B and HOMA-IR than people living without HIV. PLWH with haplogroup L2 had a slower decline in HOMA-B per year (Pinteraction = .02) and a lower risk of incident DM (hazard ratio [HR], 0.51; 95% confidence interval [CI], .32-.82) than PLWH with other haplogroups after adjustments for age, body mass index, combination antiretroviral therapy use, CD4 cell counts, and HIV RNA. The impact of HOMA-IR on incident DM was less significant in those with haplogroup L2, compared to non-L2 (HR, 1.28 [95% CI, .70-2.38] vs 4.13 [95% CI, 3.28-5.22], respectively; Pinteraction < .01), among PLWH.

Conclusions: Mitochondrial genetic variation is associated with β-cell functions and incident DM in non-Hispanic, Black women with HIV and alters the relationship between insulin resistance and DM.
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http://dx.doi.org/10.1093/cid/ciaa026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755007PMC
November 2020

Computerized cognitive performance assessments in the Brooklyn Cognitive Impairments in Health Disparities Pilot Study.

Alzheimers Dement 2019 11;15(11):1420-1426

Department of Neurology, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA. Electronic address:

Introduction: Detecting cognitive impairment in diverse, health disparities communities is an urgent health care priority.

Methods: The Brooklyn Cognitive Impairments in Health Disparities Pilot Study investigated quantitative aspects and liking of a computerized cognitive performance assessment, Cognigram, among individuals ≥ 40 years in traditional and nontraditional primary care settings.

Results: Cognigram was piloted in the Emergency Department, Family Medicine, and Geriatric Psychiatry clinics: 58 adults (23 men, 35 women), 67.9 ± 9.8 years (range 43-91), completed the Cognigram and 5-item liking survey. The observed liking range was 2 to maximum score 5 (67% scored 4-5; no sex or age differences).

Discussion: The Cognigram was well liked in waiting rooms of primary care settings. Assistance from a trained adult and clinic endorsement were keys to success. How the Cognigram performs in a geographically compact, population-dense global setting, such as Brooklyn with high vascular disease risk and a plethora of health disparities, is being tested.
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http://dx.doi.org/10.1016/j.jalz.2019.07.004DOI Listing
November 2019

White Blood Cell Counts, Lymphocyte Subsets, and Incident Diabetes Mellitus in Women Living With and Without HIV.

AIDS Res Hum Retroviruses 2020 02 17;36(2):131-133. Epub 2019 Dec 17.

Department of Medicine, Weill Cornell Medical College, New York, New York.

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.
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http://dx.doi.org/10.1089/AID.2019.0174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044769PMC
February 2020

Prevalence and Correlates of Self-Rated Successful Aging Among Older Women Living With HIV.

J Acquir Immune Defic Syndr 2019 12;82 Suppl 2:S162-S169

Emory University Nell Hodgson Woodruff School of Nursing, Atlanta, GA.

Background: Despite marked gains in longevity attributable to antiretroviral therapy (ART), older women living with HIV (OWLH) experience substantial health challenges, and few studies addressed whether they can achieve successful aging (SA). This is among the first studies examining prevalence and psychosocial correlates of self-rated SA (SRSA) among OWLH and women at risk of HIV.

Methods: The sample included 386 OWLH and 137 HIV-seronegative women enrolled in the Women's Interagency HIV Study (WIHS) who were aged 50 years and older and participated in the "From Surviving to Thriving" (FROST) substudy. The FROST survey included measures of SRSA and positive psychosocial constructs.

Results: Participants were on average 57 years (SD = 5.3), 74% African American and 30% unemployed. Among OWLH, 94% were on ART and 73% were virally suppressed. Compared with OWLH, a higher proportion of HIV-seronegative women had an annual income ≤ $6000, no health insurance, and reported lower optimism and health-related quality of life. We found no differences in SRSA prevalence by HIV status: 84% of OWLH and 83% of HIV-seronegative women reported SRSA ≥7 (range = 2-10, higher scores signify better SRSA). Having SRSA ≥7 was associated with higher levels of positive psychosocial characteristics (eg, resilience and optimism) among both OWLH and HIV-seronegative women.

Conclusions: SRSA is achievable among older women with and at risk of HIV despite health complications. Among disadvantaged women, factors other than HIV may be primary drivers of SRSA. Future research is needed to examine determinants of SRSA and to design public health interventions enhancing SA within this population.
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http://dx.doi.org/10.1097/QAI.0000000000002175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830959PMC
December 2019
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