Computationally inferred cell-type specific epigenome-wide DNA methylation analysis unveils distinct methylation patterns among immune cells for HIV infection in three cohorts.

BACKGROUND: Epigenome-wide association studies (EWAS) have identified CpG sites associated with HIV infection in blood cells in bulk, which offer limited knowledge of cell-type specific methylation patterns associated with HIV infection. In this study, we aim to identify differentially methylated CpG sites for HIV infection in immune cell types: CD4+ T-cells, CD8+ T-cells, B cells, Natural Killer (NK) cells, and monocytes. METHODS: Applying a computational deconvolution method, we performed a cell-type based EWAS for HIV infection in three independent cohorts (Ntotal = 1,382). DNA methylation in blood or in peripheral blood mononuclear cells (PBMCs) was profiled by an array-based method and then deconvoluted by Tensor Composition Analysis (TCA). The TCA-computed CpG methylation in each cell type was first benchmarked by bisulfite DNA methylation capture sequencing in a subset of the samples. Cell-type EWAS of HIV infection was performed in each cohort separately and a meta-EWAS was conducted followed by gene set enrichment analysis. RESULTS: The meta-analysis unveiled a total of 2,021 cell-type unique significant CpG sites for five inferred cell types. Among these inferred cell-type unique CpG sites, the concordance rate in the three cohorts ranged from 96% to 100% in each cell type. Cell-type level meta-EWAS unveiled distinct patterns of HIV-associated differential CpG methylation, where 74% of CpG sites were unique to individual cell types (false discovery rate, FDR <0.05). CD4+ T-cells had the largest number of unique HIV-associated CpG sites (N = 1,624) compared to any other cell type. Genes harboring significant CpG sites are involved in immunity and HIV pathogenesis (e.g. CD4+ T-cells: NLRC5, CX3CR1, B cells: IFI44L, NK cells: IL12R, monocytes: IRF7), and in oncogenesis (e.g. CD4+ T-cells: BCL family, PRDM16, monocytes: PRDM16, PDCD1LG2). HIV-associated CpG sites were enriched among genes involved in HIV pathogenesis and oncogenesis that were enriched among interferon-α and -γ, TNF-α, inflammatory response, and apoptotic pathways. CONCLUSION: Our findings uncovered computationally inferred cell-type specific modifications in the host epigenome for people with HIV that contribute to the growing body of evidence regarding HIV pathogenesis.

A web-based positive-affect intervention to reduce stress and improve well-being in women living with HIV - feasibility and acceptability of a single-arm, pilot study.

Women living with HIV (WLWH) experience high rates of depression but are underrepresented in mental health research. Positive emotions are associated with beneficial health outcomes in WLWH and should be a targeted component of psychological interventions in this population. Positive psychological interventions aim to increase positive emotions through the use of simple exercises, such as keeping a gratitude journal. We conducted a single-arm feasibility/acceptability study of a five-week, self-guided, web-based positive affect skills intervention in a sample of WLWH (N = 23) who also participate in a longitudinal observational study, the Women's Interagency HIV Study. The intervention was feasible as measured by home practice and post-intervention assessment completion, and acceptable as measured by exit interview feedback regarding recommendation of the program to friends or others living with HIV. On average, participants completed home practice for about 8 out of 9 skills. The mean response for recommendation of the program to a friend was 9.26/10 (SD = 1.63) and the mean response for recommendation of the program to others living with HIV was 9.68/10 (SD = 0.82). Participant feedback will be used to adapt and enhance the delivery of this intervention. Further studies are needed to assess efficacy and impact on psychological outcomes.

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.

Psychosocial Syndemic Classes and Longitudinal Transition Patterns Among Sexual Minority men Living with or Without HIV in the Multicenter AIDS Cohort Study (MACS).

Mental health and substance use epidemics interact to create psychosocial syndemics, accelerating poor health outcomes. Using latent class and latent transition analyses, we identified psychosocial syndemic phenotypes and their longitudinal transition pathways among sexual minority men (SMM) in the Multicenter AIDS Cohort Study (MACS, n = 3,384, mean age 44, 29% non-Hispanic Black, 51% with HIV). Self-reported depressive symptoms and substance use indices (i.e., smoking, hazardous drinking, marijuana, stimulant, and popper use) at the index visit, 3-year and 6-year follow-up were used to model psychosocial syndemics. Four latent classes were identified: "poly-behavioral" (19.4%), "smoking and depression" (21.7%), "illicit drug use" (13.8%), and "no conditions" (45.1%). Across all classes, over 80% of SMM remained in that same class over the follow-ups. SMM who experienced certain psychosocial clusters (e.g., illicit drug use) were less likely to transition to a less complex class. These people could benefit from targeted public health intervention and greater access to treatment resources.

Longitudinal Relationship Between Food Insecurity, Engagement in Care, and ART Adherence Among US Women Living with HIV.

Food insecurity disproportionately affects people with HIV and women in the United States (US). More evidence is needed to understand the interplay between levels of food insecurity and levels of antiretroviral therapy (ART) adherence over time, as well as how food insecurity relates to engagement in HIV care. We used random effects models with longitudinal data from the US Women's Interagency HIV Study to estimate the (1) adjusted associations of current and 6-month lagged food security with ART adherence categories (n = 1646), and (2) adjusted associations of food security with engagement-in-care (n = 1733). Very low food security was associated with a higher relative risk of ART non-adherence at prior and current visits compared with food security, and this association increased across non-adherence categories. Very low food security was associated with lower odds of receiving HIV care and higher odds of a missed visit. Food insecurity among US women with HIV is associated with poorer engagement in care and degree of ART non-adherence over time.

Dual trajectories of antiretroviral therapy adherence and polypharmacy in women with HIV in the United States.

BACKGROUND: Polypharmacy, using five or more medications, may increase the risk of nonadherence to prescribed treatment. We aimed to identify the interrelationship between trajectories of adherence to antiretroviral therapy (ART) and polypharmacy. METHODS: We included women with HIV (aged ≥ 18) enrolled in the Women's Interagency HIV Study in the United States from 2014 to 2019. We used group-based trajectory modeling (GBTM) to identify trajectories of adherence to ART and polypharmacy and the dual GBTM to identify the interrelationship between adherence and polypharmacy. RESULTS: Overall, 1,538 were eligible (median age of 49 years). GBTM analysis revealed five latent trajectories of adherence with 42% of women grouped in the consistently moderate trajectory. GBTM identified four polypharmacy trajectories with 45% categorized in the consistently low group. CONCLUSIONS: The joint model did not reveal any interrelationship between ART adherence and polypharmacy trajectories. Future research should consider examining the interrelationship between both variables using objective measures of adherence.

A new monocyte epigenetic clock reveals nonlinear effects of alcohol consumption on biological aging in three independent cohorts (N = 2242).

BACKGROUND: Assessing the effect of alcohol consumption on biological age is essential for understanding alcohol use-related comorbidities and mortality. Previously developed epigenetic clocks are mainly based on DNA methylation in heterogeneous cell types, which provide limited knowledge on the impacts of alcohol consumption at the individual cellular level. Evidence shows that monocytes play an important role in both alcohol-induced pathophysiology and the aging process. In this study, we developed a novel monocyte-based DNA methylation clock (MonoDNAmAge) to assess the impact of alcohol consumption on monocyte age. METHODS: A machine learning method was applied to select a set of chronological age-associated DNA methylation CpG sites from 1202 monocyte methylomes. Pearson correlation was tested between MonoDNAmAge and chronological age in three independent cohorts (Ntotal  = 2242). Using the MonoDNAmAge clock and four established clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge), we then evaluated the effect of alcohol consumption on epigenetic aging in the three cohorts [i.e., Yale Stress Center Community Study (YSCCS), Veteran Aging Cohort Study (VACS), Women's Interagency HIV Study (WIHS)] using linear and quadratic models. RESULTS: The MonoDNAmAge, comprised of 186 CpG sites, was moderately to strongly correlated with chronological age in the three cohorts (r = 0.90, p = 3.12E-181 in YSCCS; r = 0.54, p = 1.75E-96 in VACS; r = 0.66, p = 1.50E-60 in WIHS). More importantly, we found a nonlinear association between MonoDNAmAge and alcohol consumption (pmodel  = 4.55E-08, px2  = 7.80E-08 in YSCCS; pmodel  = 1.85E-02, px2  = 3.46E-02 in VACS). Heavy alcohol consumption increased EAAMonoDNAmAge up to 1.60 years while light alcohol consumption decreased EAAMonoDNAmAge up to 2.66 years. These results were corroborated by the four established epigenetic clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge). CONCLUSIONS: The results suggest a nonlinear relationship between alcohol consumption and its effects on epigenetic age. Considering adverse effects of alcohol consumption on health, nonlinear effects of alcohol use should be interpreted with caution. The findings, for the first time, highlight the complex effects of alcohol consumption on biological aging.

Intensity of Social Support Matters: A Latent Class Analysis to Identify Levels of Social Support Associated with Optimal Health Outcomes Among Women Living with HIV.

Social support is associated with improved HIV care and quality of life. We utilized latent class analysis to identify three classes of baseline emotional and tangible perceived social support, termed "Strong", "Wavering" and "Weak". "Weak" vs. "Strong" perceived social support was associated over time with an 8% decreased risk of optimal antiretroviral therapy (ART) adherence for emotional and 6% decreased risk for tangible perceived social support. Importantly, "Wavering" vs "Strong" social support also showed a decreased risk of ART adherence of 6% for emotional and 3% for tangible support. "Strong" vs. "Weak" perceived support had a similar association with undetectable viral load, but the association for "Strong" vs. "Wavering" support was not statistically significant. Intensity of social support is associated with HIV care outcomes, and strong social support may be needed for some individuals. It is important to quantify the level or intensity of social support that is needed to optimize HIV outcomes.

RESUMEN: El apoyo social está asociado con una mejor atención y calidad de vida del virus de inmunodeficiencia humana (VIH). Utilizamos el análisis de clase latente para identificar tres clases de apoyo social percibido emocional y tangible de referencia, denominado "fuerte", "vacilante" y "débil". El apoyo social percibido "débil" versus el "fuerte" se asoció con el tiempo con una disminución del 8% en el riesgo de una adherencia óptima al terapia antirretroviral (TAR) para el apoyo emocional y del 6% en el riesgo de un apoyo social percibido tangible. Es importante destacar que el apoyo social "vacilante" frente a "fuerte" también mostró una disminución del riesgo de adherencia al TAR del 6% para el apoyo emocional y del 3% para el apoyo tangible. El apoyo percibido "fuerte" frente a "débil" tuvo una asociación similar con una carga viral indetectable, pero la asociación entre el apoyo "fuerte" y el apoyo "vacilante" no fue estadísticamente significativa. La intensidad del apoyo social está asociada con los resultados de la atención del VIH, y algunas personas pueden necesitar un fuerte apoyo social. Es importante cuantificar el nivel o la intensidad del apoyo social que se necesita para optimizar los resultados del VIH.

Long-Acting Injectable ART and PrEP Among Women in Six Cities Across the United States: A Qualitative Analysis of Who Would Benefit the Most.

Long-acting injectable (LAI) modalities have been developed for ART and PrEP. Women face unique barriers to LAI use yet little research has examined women's perceptions of potential LAI HIV therapy candidates. We conducted 89 in-depth interviews at six Women's Interagency HIV Study (WIHS) sites with women living with HIV (n = 59) and HIV-negative women (n = 30) from 2017 to 2018. Interviews were recorded, transcribed, and analyzed using thematic content analysis. Participants identified specific sub-populations who could most benefit from LAI over daily pills: (1) young people; (2) women with childcare responsibilities; (3) people with adherence-related psychological distress; (4) individuals with multiple sex partners; and (5) people facing structural insecurities such as homelessness. Women are underserved by current HIV care options and their perspectives are imperative to ensure a successful scale-up of LAI PrEP and LAI ART that prioritizes equitable access and benefit for all individuals.

Patient Health Literacy and Communication with Providers Among Women Living with HIV: A Mixed Methods Study.

In this mixed-methods study, we examine the relationship between provider communication and patient health literacy on HIV continuum of care outcomes among women living with HIV in the United States. We thematically coded qualitative data from focus groups and interviews (N = 92) and conducted mediation analyses with quantitative survey data (N = 1455) collected from Women's Interagency HIV Study participants. Four qualitative themes related to provider communication emerged: importance of respect and non-verbal cues; providers' expressions of condescension and judgement; patient health literacy; and unclear, insufficient provider communication resulting in diminished trust. Quantitative mediation analyses suggest that higher health literacy is associated with higher perceived patient-provider interaction quality, which in turn is associated with higher levels of trust in HIV providers, improved antiretroviral medication adherence, and reduced missed clinical visits. Findings indicate that enhancing provider communication and bolstering patient health literacy could have a positive impact on the HIV continuum of care.

RESUMEN: En este estudio de métodos mixtos, examinamos la relación entre la comunicación del proveedor y la alfabetización sanitaria del paciente sobre los resultados de la atención continua del VIH entre las mujeres que viven con el VIH en los Estados Unidos. Codificamos temáticamente datos cualitativos de grupos focales y entrevistas (N = 92) y realizamos análisis de mediación con datos de encuestas cuantitativas (N = 1455) recopilados de participantes del Estudio de VIH entre agencias de mujeres. Surgieron cuatro temas cualitativos relacionados con la comunicación con el proveedor: la importancia del respeto y las señales no verbales; las expresiones de condescendencia y juicio de los proveedores; alfabetización en salud del paciente; y una comunicación poco clara e insuficiente con el proveedor que da como resultado una disminución de la confianza. Los análisis de mediación cuantitativa sugieren que una mayor alfabetización en salud se asocia con una mayor calidad de interacción percibida entre el paciente y el proveedor, que a su vez se asocia con niveles más altos de confianza en los proveedores de VIH, una mejor adherencia a la medicación antirretroviral y una reducción de las visitas clínicas perdidas. Los resultados indican que mejorar la comunicación con los proveedores y reforzar la alfabetización sanitaria del paciente podría tener un impacto positivo en la atención continua del VIH.

Positive Psychological Factors and Life Themes in Relation to Health Outcomes in Women Living with HIV.

BACKGROUND: This mixed methods study identified positive psychological factors and life themes expressed in autobiographical narratives of predominantly Black women living with HIV (WLWH) and investigated these in relation to depressive symptoms, antiretroviral therapy (ART) adherence (≥ 95% of time), and undetectable HIV viral load (VL) (< 80 copies/ml). METHOD: Ninety-eight WLWH from the Women's Interagency HIV Study Chicago site (M age = 45.3; 91% Black) narrated three autobiographical life turning points, reliably coded for positive factors and life themes. ART adherence, VL and depressive symptoms, assessed with Center for Epidemiologic Studies Depression Scale total score (TOT) including its four factors (negative affect (NA), positive affect (PA), somatic symptoms (SS), and interpersonal problems (IP)), were collected over two time points: concurrently with narratives and 6 months later. Composite scores across the two time points were used in all analyses. RESULTS: Ten positive psychological factors (gratitude, insight, compassion, meaning-making, acceptance, mindfulness, generativity, optimism, self-reliance, and benevolent God beliefs) and three positive life themes (health improvements, positive relationships, and accomplishments) were identified in narratives. Higher accomplishments, overall positive factors, insight, mindfulness, self-reliance, optimism, meaning-making, and acceptance related to lower depressive symptoms (TOT, NA, SS, or IP). Positive factors and life themes did not significantly relate to PA. Higher compassion related to higher ART adherence. Higher accomplishments related to undetectable VL independent of ART adherence. CONCLUSION: Findings that positive psychological factors and life accomplishments may relate to better health, especially to lower depression, potentially contribute to developing positive psychology interventions for Black WLWH.

Direct-Acting Antiviral Hepatitis C Treatment Cascade and Barriers to Treatment Initiation Among US Men and Women With and Without HIV.

BACKGROUND: People with HIV are disproportionately coinfected with hepatitis C virus (HCV) and experience accelerated liver-related mortality. Direct-acting antivirals (DAAs) yield high sustained virologic response (SVR) rates, but uptake is suboptimal. This study characterizes the DAA-era HCV treatment cascade and barriers among US men and women with or at risk for HIV. METHODS: We constructed HCV treatment cascades using the Women's Interagency HIV Study (women, 6 visits, 2015-2018, n = 2447) and Multicenter AIDS Cohort Study (men, 1 visit, 2015-2018, n = 2221). Cascades included treatment-eligible individuals (ie, HCV RNA-positive or reported DAAs). Surveys captured self-reported clinical (eg, CD4), patient (eg, missed visits), system (eg, appointment access), and financial/insurance barriers. RESULTS: Of 323/92 (women/men) treatment eligible, most had HIV (77%/70%); 69%/63% were black. HIV-positive women were more likely to attain cascade outcomes than HIV-negative women (39% vs 23% initiated, 21% vs 12% SVR); similar discrepancies were noted for men. Black men and substance users were treated less often. Women initiating treatment (vs not) reported fewer patient barriers (14%/33%). Among men not treated, clinical barriers were prevalent (53%). CONCLUSIONS: HIV care may facilitate HCV treatment linkage and barrier navigation. HIV-negative individuals, black men, and substance users may need additional support. CLINICAL TRIALS REGISTRATION: NCT00000797 (Women's Interagency HIV Study); NCT00046280 (Multicenter AIDS Cohort Study).

Food Insecurity and T-cell Dysregulation in Women Living With Human Immunodeficiency Virus on Antiretroviral Therapy.

BACKGROUND: Food insecurity is associated with increased morbidity and mortality in people with human immunodeficiency virus (HIV) on antiretroviral therapy, but its relationship with immune dysregulation, a hallmark of HIV infection and comorbidity, is unknown. METHODS: In 241 women participating in the Women's Interagency HIV Study, peripheral blood mononuclear cells were characterized by flow cytometry to identify cell subsets, comprising surface markers of activation (%CD38+HLADR+), senescence (%CD57+CD28-), exhaustion (%PD-1+), and co-stimulation (%CD57- CD28+) on CD4+ and CD8+ T cells. Mixed-effects linear regression models were used to assess the relationships of food insecurity with immune outcomes, accounting for repeated measures at ≤3 study visits and adjusting for sociodemographic and clinical factors. RESULTS: At the baseline study visit, 71% of participants identified as non-Hispanic Black, 75% were virally suppressed, and 43% experienced food insecurity. Food insecurity was associated with increased activation of CD4+ and CD8+ T cells, increased senescence of CD8+ T cells, and decreased co-stimulation of CD4+ and CD8+ T cells (all P < .05), adjusting for age, race/ethnicity, income, education, substance use, smoking, HIV viral load, and CD4 count. In stratified analyses, the association of food insecurity with CD4+ T-cell activation was more pronounced in women with uncontrolled HIV (viral load >40 copies/mL and CD4 <500 cells/mm3) but remained statistically significant in those with controlled HIV. CONCLUSIONS: Food insecurity may contribute to the persistent immune activation and senescence in women with HIV on antiretroviral therapy, independently of HIV control. Reducing food insecurity may be important for decreasing non-AIDS-related disease risk in this population.

Characteristics of the MACS/WIHS Combined Cohort Study: Opportunities for Research on Aging With HIV in the Longest US Observational Study of HIV.

In 2019, the National Institutes of Health combined the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS) into the MACS/WIHS Combined Cohort Study (MWCCS). In this paper, participants who made a study visit during October 2018-September 2019 (targeted for MWCCS enrollment) are described by human immunodeficiency virus (HIV) serostatus and compared with people living with HIV (PLWH) in the United States. Participants include 2,115 women and 1,901 men with a median age of 56 years (interquartile range, 48-63); 62% are PLWH. Study sites encompass the South (18%), the Mid-Atlantic/Northeast (45%), the West Coast (22%), and the Midwest (15%). Participant race/ethnicity approximates that of PLWH throughout the United States. Longitudinal data and specimens collected for 35 years (men) and 25 years (women) were combined. Differences in data collection and coding were reviewed, and key risk factor and comorbidity data were harmonized. For example, recent use of alcohol (62%) and tobacco (28%) are common, as are dyslipidemia (64%), hypertension (56%), obesity (42%), mildly or severely impaired daily activities (31%), depressive symptoms (28%), and diabetes (22%). The MWCCS repository includes serum, plasma, peripheral blood mononuclear cells, cell pellets, urine, cervicovaginal lavage samples, oral samples, B-cell lines, stool, and semen specimens. Demographic differences between the MACS and WIHS can confound analyses by sex. The merged MWCCS is both an ongoing observational cohort study and a valuable resource for harmonized longitudinal data and specimens for HIV-related research.

Poverty, Deprivation, and Mortality Risk Among Women With HIV in the United States.

BACKGROUND: Prior studies suggest neighborhood poverty and deprivation are associated with adverse health outcomes including death, but evidence is limited among persons with HIV, particularly women. We estimated changes in mortality risk from improvement in three measures of area-level socioeconomic context among participants of the Women's Interagency HIV Study. METHODS: Starting in October 2013, we linked geocoded residential census block groups to the 2015 Area Deprivation Index (ADI) and two 2012-2016 American Community Survey poverty variables, categorized into national tertiles. We used parametric g-computation to estimate, through March 2018, impacts on mortality of improving each income or poverty measure by one and two tertiles maximum versus no improvement. RESULTS: Of 1596 women with HIV (median age 49), 91 (5.7%) were lost to follow-up and 83 (5.2%) died. Most women (62%) lived in a block group in the tertile with the highest proportions of individuals with income:poverty <1; 13% lived in areas in the tertile with the lowest proportions. Mortality risk differences comparing a one-tertile improvement (for those in the two highest poverty tertiles) in income:poverty <1 versus no improvement increased over time; the risk difference was -2.2% (95% confidence interval [CI] = -3.7, -0.64) at 4 years. Estimates from family income below poverty level (-1.0%; 95% CI = -2.7, 0.62) and ADI (-1.5%; 95% CI = -2.8, -0.21) exposures were similar. CONCLUSIONS: Consistent results from three distinct measures of area-level socioeconomic environment support the hypothesis that interventions to ameliorate neighborhood poverty or deprivation reduce mortality risk for US women with HIV. See video abstract at, http://links.lww.com/EDE/B863.

Interest in Long-Acting Injectable Pre-exposure Prophylaxis (LAI PrEP) Among Women in the Women's Interagency HIV Study (WIHS): A Qualitative Study Across Six Cities in the United States.

Long-acting injectable (LAI) pre-exposure prophylaxis (PrEP) has the potential to facilitate adherence and transform HIV prevention. However, little LAI PrEP research has occurred among women, who face unique barriers. We conducted 30 in-depth interviews with HIV-negative women from 2017-2018 across six sites (New York; Chicago; San Francisco; Atlanta; Washington, DC; Chapel Hill) of the Women's Interagency HIV Study. Interviews were recorded, transcribed, and analyzed using thematic content analysis. Few women expressed interest in PrEP and when prompted to choose a regimen, 55% would prefer LAI, 10% daily pills, and 33% said they would not take PrEP regardless of formulation. Perceived barriers included: (1) the fear of new-and perceived untested-injectable products and (2) potential side effects (e.g., injection-site pain, nausea). Facilitators included: (1) believing shots were more effective than pills; (2) ease and convenience; and (3) confidentiality. Future studies should incorporate women's LAI PrEP-related experiences to facilitate uptake.

Associations between population density and clinical and sociodemographic factors in women living with HIV in the Southern United States.

To explore the associations of urbanicity with clinical/behavioral outcomes and sociodemographic factors among women living with HIV in the Southern United States, 523 participants of the Women's Interagency HIV Study were classified into population density quartiles. Rural-Urban Commuting Area codes revealed that 7% resided in areas where >30% commute to urban areas, 2% resided in small towns or rural areas, and 91% resided in varying densities of urban areas. Although women in lower density, mostly suburban areas reported higher socioeconomic indicators such as advanced education and greater annual household income, larger proportions of women in the lowest density quartile perceived discrimination in health care settings and agreed with several internalized HIV stigma scale items. Women in the lower quartiles had higher CD4 counts, while those in the lowest quartile were more likely to have a suppressed HIV viral load, report being employed, and not report a history of drug use or current heavy alcohol use. More research is needed to understand the interplay between population density and mechanisms contributing to HIV control as well as increased internalized stigma and perceived discrimination, along with how to target interventions to improve outcomes for individuals with HIV across urban, suburban, and rural areas.

Health insurance and AIDS Drug Assistance Program (ADAP) increases retention in care among women living with HIV in the United States.

Our objective was to examine the association between healthcare payer type and missed HIV care visits among 1,366 US women living with HIV (WLWH) enrolled in the prospective Women's Interagency HIV Study (WIHS). We collected secondary patient-level data (October 1, 2017-September 30, 2018) from WLWH at nine WIHS sites. We used bivariate and multivariable binary logistic regression to examine the relationship between healthcare payer type (cross-classification of patients' ADAP and health insurance enrollment) and missed visits-based retention in care, defined as no-show appointments for which patients did not reschedule. Our sample included all WLWH who self-reported having received HIV care at least once during the two consecutive biannual WIHS visits a year prior to October 1, 2017-September 30, 2018. In the bivariate model, compared to uninsured WLWH without ADAP, WLWH with private insurance + ADAP were more likely to be retained in care, as were WLWH with Medicaid only and private insurance only. In the adjusted model, WLWH with private insurance only were more likely to be retained in care compared to uninsured WLWH without ADAP. Private health insurance and ADAP are associated with increased odds of retention in care among WLWH.

Associations of CKD risk factors and longitudinal changes in urine biomarkers of kidney tubules among women living with HIV.

BACKGROUND: Novel urine biomarkers have enabled the characterization of kidney tubular dysfunction and injury among persons living with HIV, a population at an increased risk of kidney disease. Even though several urine biomarkers predict progressive kidney function decline, antiretroviral toxicity, and mortality in the setting of HIV infection, the relationships among the risk factors for chronic kidney disease (CKD) and urine biomarkers are unclear. METHODS: We assessed traditional and infection-related CKD risk factors and measured 14 urine biomarkers at baseline and at follow-up among women living with HIV in the Women's Interagency Health Study (WIHS). We then used simultaneously adjusted multivariable linear regression models to evaluate the associations of CKD risk factors with longitudinal changes in biomarker levels. RESULTS: Of the 647 women living with HIV in this analysis, the majority (67%) were Black, the median age was 45 years and median follow-up time was 2.5 years. Each traditional and infection-related CKD risk factor was associated with a unique set of changes in urine biomarkers. For example, baseline hemoglobin a1c was associated with worse tubular injury (higher interleukin [IL]-18), proximal tubular reabsorptive dysfunction (higher α1-microglobulin), tubular reserve (lower uromodulin) and immune response to injury (higher chitinase-3-like protein-1 [YKL-40]). Furthermore, increasing hemoglobin a1c at follow-up was associated with further worsening of tubular injury (higher kidney injury molecule-1 [KIM-1] and IL-18), as well as higher YKL-40. HCV co-infection was associated with worsening proximal tubular reabsorptive dysfunction (higher ß2-microglobulin [ß2m]), and higher YKL-40, whereas HIV viremia was associated with worsening markers of tubular and glomerular injury (higher KIM-1 and albuminuria, respectively). CONCLUSIONS: CKD risk factors are associated with unique patterns of biomarker changes among women living with HIV, suggesting that serial measurements of multiple biomarkers may help in detecting and monitoring kidney disease in this setting.

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

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 ß-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 ß-cell functions and incident DM in non-Hispanic, Black women with HIV and alters the relationship between insulin resistance and DM.