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ObjectiveSexual and physical abuse predict cardiovascular disease (CVD) among women in the general population. Women living with HIV (WLWH) report more abuse and have higher CVD risk compared with other women, yet associations between abuse history and CVD have not been considered among WLWH. This study fills this gap, and describes possible pathways linking abuse to CVD risk among WLWH and women living without HIV (WLWOH).MethodsUsing 25 years of data from the Women's Interagency HIV Study (WIHS; n  = 2734; WLWH n  = 1963; WLWOH n  = 771), we used longitudinal generalized estimating equations (GEE) to test associations between sexual and physical abuse with CVD risk. Framingham (FRS-H) and the American College of Cardiology/American Heart Association-Pooled Cohort Equation (ACC/AHA-PCE) scores were examined. Analyses were stratified by HIV-serostatus.ResultsAmong WLWH, childhood sexual abuse was associated with higher CVD risk ( βFRS-H  = 1.25, SE = 1.08, P  = 0.005; βACC/AHA-PCE  = 1.14, SE = 1.07, P  = 0.04) compared with no abuse. Adulthood sexual abuse was associated with higher CVD risk for WLWH ( βFRS-H  = 1.39, SE = 1.08, P

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.

BackgroundHeavy drinking, smoking, and depression are common among people with HIV. Little is known about the co-occurring, synergistic effect of having two or more of these conditions long-term -a sustained syndemic - on mortality among women with HIV (WWH).MethodsData from 3282 WWH of the Women's Interagency HIV Study from 1994 to 2017 were utilized. National Death Index review identified cause of death (n=616). Sustained syndemic phenotypes were based on membership in high-risk groups defined by group-based trajectory models of repeated self-reported alcohol use, smoking, and depressive symptoms and their co-occurrence. Cox proportional hazard models estimated associations of sustained syndemic phenotypes with all-cause, non-AIDS, and non-overdose mortality, adjusting for age, race/ethnicity, education, enrollment wave, illicit drug use, and time-varying HIV viral load and CD4+ T-cell count.ResultsWWH were 58% Black and 26% Hispanic, with a mean baseline age of 36.7 years. Syndemic phenotypes included zero (45%, n=1463), heavy drinking only (1%, n=35), smoking only (28%, n=928), depressive symptoms only (9%, n=282), and 2+ trajectories (17%, n=574). Compared to zero trajectories, having 2+ trajectories was associated with 3.93 times greater all-cause mortality risk (95% CI 3.07, 5.04) after controlling for confounders and each high-risk trajectory alone. These findings persisted in sensitivity analyses, removing AIDS- and overdose-related mortalities.ConclusionsClustering of 2+ conditions of heavy drinking, smoking, and depression affected nearly one in five WWH and was associated with higher mortality than zero or one condition. Our findings underscore the need for coordinated screening and parsimonious treatment strategies for these co-occurring conditions.

BackgroundSubstance use (SU) contributes to poor health outcomes, yet limited data exist to inform strategies to optimize SU treatment among persons with human immunodeficiency virus (HIV). We describe SU and SU treatment utilization among women with and without HIV in the Women's Interagency HIV Study (WIHS).MethodsWe included data from women enrolled in WIHS from 2013 to 2020. Current SU was self-reported, nonmedical use of drugs in the past year, excluding use of only marijuana. SU treatment utilization was self-reported use of a drug treatment program in the past year. Multivariable regression models were used to investigate associations between participant characteristics and SU treatment.ResultsAmong 2559 women (1802 women living with HIV [WWH], 757 women without HIV), 14% reported current SU. Among those with current SU (n = 367), 71% reported crack/cocaine followed by 40% reporting opioids, and 42% reported any treatment in the past year. The most common treatments were methadone (64%), Narcotics Anonymous (29%), inpatient programs (28%), and outpatient programs (16%). Among women using opioids (n = 147), 67% reported methadone use in the past year compared to 5% using buprenorphine/naloxone. Multivariable analysis showed lower odds of treatment utilization among WWH with concurrent alcohol or marijuana use. Visiting a psychiatrist/counselor was associated with higher odds of treatment. Among WWH, SU treatment was not associated with HIV-related clinical outcomes.ConclusionsTreatment utilization was high, especially for methadone use. Our results highlight opportunities for accessing SU treatment for WWH, such as the need to prioritize buprenorphine and comprehensive, wraparound services in HIV care settings.

Resilience and optimism may not only have main effects on health outcomes, but may also moderate and buffer negative effects of stressors. We examined whether dispositional resilience and optimism moderate the associations between HIV-related stigma in health care settings and health-related outcomes (trust in HIV health care providers and depression symptoms) among women living with HIV (WLHIV). One thousand four hundred five WLHIV in nine US cities completed validated questionnaires for cross-sectional analyses. Higher self-reported experienced and anticipated stigma and lower resilience and optimism were associated with higher depression symptoms and with lower trust in HIV providers. Importantly, resilience moderated the effects of experienced stigma (but not of anticipated stigma): When resilience was high, the association of experienced stigma with higher depression symptoms and lower trust in HIV providers was weaker compared with when resilience was low. Further, significant moderation effects suggested that when optimism was high, experienced and anticipated stigma was both less strongly associated with depression symptoms and with lower trust in one's HIV care providers compared with when optimism was low. Thus, the effects of experienced stigma on depression symptoms and provider trust were moderated by both resilience and optimism, but the effects of anticipated stigma were moderated only by optimism. Our findings suggest that in addition to their main effects, resilience and optimism may function as buffers against the harmful effects of stigma in health care settings. Therefore, optimism and resilience may be valuable intervention targets to reduce depression symptoms or improve trust in providers among populations that experience or anticipate stigma, such as WLHIV.

Rationale: Human immunodeficiency virus (HIV) infection is associated with chronic lung disease and impaired pulmonary function; however, longitudinal pulmonary function phenotypes in HIV are undefined. Objectives: To identify pulmonary function trajectories, their determinants, and outcomes. Methods: We used data from participants with HIV in the Pittsburgh HIV Lung Cohort with three or more pulmonary function tests between 2007 and 2020. We analyzed post-bronchodilator forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC, and diffusing capacity of the lung for carbon monoxide (DlCO) using group-based trajectory modeling to identify subgroups of individuals whose measurements followed a similar pattern over time. We examined the association between participant characteristics and trajectories using multivariable logistic regression. In exploratory adjusted analyses restricted to individuals with available plasma cytokine data, we investigated the association between 18 individual standardized cytokine concentrations and trajectories. We compared mortality, dyspnea prevalence, respiratory health status, and 6-minute-walk distance between phenotypes. Results: A total of 265 participants contributed 1,606 pulmonary function measurements over a median follow-up of 8.1 years. We identified two trajectories each for FEV1 and FVC: "low baseline, slow decline" and "high baseline, rapid decline." There were three trajectory groups for FEV1/FVC: "rapid decline," "moderate decline," and "slow decline." Finally, we identified two trajectories for DlCO: "baseline low" and "baseline high." The low baseline, slow decline FEV1 and FVC, rapid decline, and moderate decline FEV1/FVC, and baseline low DlCO phenotypes were associated with increased dyspnea prevalence, worse respiratory health status, and decreased 6-minute-walk distance. The baseline low DlCO phenotype was also associated with worse mortality. Current smoking and pack-years of smoking were associated with the adverse FEV1, FEV1/FVC, and DlCO phenotypes. Detectable viremia was the only HIV marker associated with the adverse DlCO phenotype. C-reactive protein and endothelin-1 were associated with the adverse FEV1 and FVC phenotypes, and endothelin-1 trended toward an association with the adverse DlCO phenotype. Conclusions: We identified novel, distinct longitudinal pulmonary function phenotypes with significant differences in characteristics and outcomes. These findings highlight the importance of lung dysfunction over time in people with HIV and should be validated in additional cohorts.

ObjectiveTo test whether substance use mediates the associations between gender-based violence (GBV) and suboptimal adherence to antiretroviral therapy (ART), and GBV and poor engagement in care, among women living with HIV (WLHIV) in the United States (US).DesignWe analyzed longitudinal data collected among 1717 WLHIV in the Women's Interagency HIV Study (WIHS).MethodsFrom 2013 to 2017, WLHIV completed semi-annual assessments on GBV, substance use, and HIV treatment and care. Adjusted multilevel logistic regression models were built to estimate the impact of GBV on; suboptimal (

Neuropsychiatric complications are common among women with HIV (WWH). The pathophysiological mechanisms underlying these complications are not fully known but likely driven in part by immune modulation. We examined associations between T-cell activation states which are required to mount an effective immune response (activation, co-stimulation/normal function, exhaustion, senescence) and neuropsychiatric complications in WWH. 369 WWH (78% HIV RNA undetectable/

The prevalence of HIV-associated neurocognitive impairment persists despite highly effective antiretroviral therapy (ART). In this study we explore the role of internalized stigma, acceptance of negative societal characterizations, and perceptions about people living with HIV (PLWH) on neurocognitive functioning (executive function, learning, memory, attention/working memory, psychomotor speed, fluency, motor skills) in a national cohort of women living with HIV (WLWH) in the United States. We utilized observational data from a multicenter study of WLWH who are mostly African American living in low-resource settings. Neurocognitive function was measured using an eight-test battery. A multiple linear regression model was constructed to investigate the relationship between internalized stigma and overall neurocognitive functioning (mean of all neurocognitive domain standardized T-scores), adjusting for age, education, race, previous neuropsychological battery scores, illicit drug use, viral load, and years on ART. Our analysis revealed that internalized HIV-related stigma is significantly associated with worse performance on individual domain tests and overall neurocognitive performance (B = 0.27, t = 2.50, p = 0.01). This suggests HIV-related internalized stigma may be negatively associated with neurocognitive functioning for WLWH. This finding highlights a specific psychosocial factor associated with poor neurocognitive function that may be targeted to better promote the health of PLWH. Future research on the longitudinal relationship between these variables and the effects of other stigma dimensions on poor neurocognitive function would provide further insights into the pathways explaining the relationship between internalized stigma and neurocognition.

BackgroundAs employment, financial status, and residential location change, people can gain, lose, or switch health insurance coverage, which may affect care access and health. Among Women's Interagency HIV Study participants with HIV and participants at risk for HIV attending semiannual visits at 10 U.S. sites, we examined whether the prevalence of coverage types and rates of coverage changes differed by HIV status and Medicaid expansion in their states of residence.MethodsGeocoded addresses were merged with dates of Medicaid expansion to indicate, at each visit, whether women lived in Medicaid expansion states. Age-adjusted rate ratios (RRs) and rate differences of self-reported insurance changes were estimated by Poisson regression.ResultsFrom 2008 to 2018, 3,341 women (67% Black, 71% with HIV) contributed 43,329 visits at aged less than 65 years (27% under Medicaid expansion). Women with and women without HIV differed in their proportions of visits at which no coverage (14% vs. 19%; p

ObjectivesThis study of people with HIV (PWH) and those without HIV conducted during the COVID-19 pandemic in the United States in 2020 examines the impact of posttraumatic stress disorder (PTSD) on COVID-19 burden, defined as pandemic-related disruptions.MethodsData consisted of survey responses on PTSD among participants (N = 2434) enrolled in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV (WIHS) cohorts. Unadjusted and adjusted regression models were used to examine the association of PTSD with COVID-19 burden (overall and domain-specific burdens). Quasi-Poisson regression models were used to assess associations with the COVID-19 burden score and 2 domain-specific burdens: (1) changes in resources and (2) interruptions in health care. Analyses was adjusted for age, race/ethnicity, HIV serostatus, current smoking status, number of comorbidities, education, and study regions.ResultsStudy participants were a median age of 58 (interquartile range, 52-65) years. In both bivariate and multivariable models, PTSD severity was associated with greater overall COVID-19 burden. PTSD severity was associated with the number of resource changes and number of interruptions in medical care. These findings were also consistent across cohorts (MACS/WIHS) and across HIV serostatus, suggesting a greater risk for COVID-19 burden with greater PTSD severity, which remained significant after controlling for covariates.ConclusionsThis study builds on emerging literature demonstrating the impact of mental health on the burden and disruption associated with the COVID-19 pandemic, providing context specific to PWH. The ongoing pandemic requires structural and social interventions to decrease disruption to resources and health resource needs among these vulnerable populations.

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.

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.

BackgroundGender-based violence (GBV) is associated with poorer engagement in HIV care and treatment. However, there is a dearth of research on the psychological (eg, mental health) and structural (eg, food insecurity) factors that mediate and moderate this association. GBV could lead to poor mental health, which in turn affects adherence, whereas food insecurity could worsen the effect of GBV on engagement in care. This study uses data from the Women's Interagency HIV Study to address these gaps.MethodsWomen completed 6 assessments from 2013 to 2016 on GBV, mental health, food insecurity, adherence to antiretroviral therapy, and missed HIV care appointments in the past 6 months. Multilevel logistic regression models estimated associations between GBV and engagement in care and whether associations were mediated by depression, generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD) and moderated by food insecurity.ResultsGBV was associated with higher odds of suboptimal adherence (adjusted odds ratio: 1.88; 95% confidence interval: 1.24 to 2.87) and missed appointments (adjusted odds ratio: 1.76; 95% confidence interval: 1.16 to 2.67). The association between GBV and adherence was mediated by depressive symptoms, GAD, and PTSD, accounting for 29.7%, 15.0%, and 16.5%, respectively, of the total association. The association between GBV and missed appointments was mediated by depression and GAD, but not PTSD, with corresponding figures of 25.2% and 19.7%. Associations did not differ by food insecurity.ConclusionsGBV is associated with suboptimal engagement in care, which may be explained by mental health. Interventions should address women's mental health needs, regardless of food insecurity, when improving engagement in HIV care.

BackgroundAt the start of the COVID-19 pandemic, HIV experts suggested that an increase in mental health diagnoses and substance use among people living with HIV (PLHIV) may be an unintended consequence of COVID-19 mitigation efforts (e.g., limiting social contact). We evaluated short-term trajectories in binge drinking, marijuana, and recreational drug use in a prospective cohort of PLHIV.MethodsData (N = 2121 PLHIV) consist of survey responses on substance use behaviors from two pre-COVID-19 (October 2018-September 2019) and one COVID-19-era (April 2020-September 2020) timepoints within the MACS/WIHS Combined Cohort Study (MWCCS). We conducted group-based trajectory models, triangulated with generalized linear mixed models, to assess changes in binge drinking, daily marijuana use, and recreational drug use at the start of the pandemic. Controlling for age and race/ethnicity, we tested whether trajectories differed by sex and early-pandemic depressive symptoms, loneliness, and social support.ResultsGroup-based trajectory models yielded two trajectory groups for binge drinking (none vs. any), marijuana (none/infrequent vs. daily), and recreational drug use (none vs. any). Binge drinking and recreational drug use decreased at the beginning of the pandemic. Generalized linear mixed model supported these trends. Consistent with prior research, male sex and having depressive symptoms early pandemic were positively associated with each substance use outcomes. Social support was inversely associated with recreational drug use.ConclusionsContrary to hypotheses, problematic substance use behaviors decreased from pre-pandemic to the post-pandemic follow-up in our sample of PLHIV. Ongoing surveillance is needed to assess whether this pattern persists as the pandemic continues.

ObjectivesThis study describes prevention behavior and psychosocial health among people living with HIV (PLHIV) and HIV-negative people during the early wave of the coronavirus disease 2019 (COVID-19) pandemic in the United States. We assessed differences by HIV status and associations between social disruption and psychosocial health.DesignA cross-sectional telephone/videoconference administered survey of 3411 PLHIV and HIV-negative participants in the Multicenter AIDS Cohort Study/WIHS Combined Cohort Study (MWCCS).MethodsAn instrument combining new and validated measures was developed to assess COVID-19 prevention efforts, social disruptions (loss of employment, childcare, health insurance, and financial supports), experiences of abuse, and psychosocial health. Interviews were performed between April and June 2020. Associations between social disruptions and psychosocial health were explored using multivariable logistic regression, adjusting for sociodemographics and HIV status.ResultsAlmost all (97.4%) participants reported COVID-19 prevention behavior; 40.1% participants reported social disruptions, and 34.3% reported health care appointment disruption. Men living with HIV were more likely than HIV-negative men to experience social disruptions (40.6% vs. 32.9%; P < 0.01), whereas HIV-negative women were more likely than women with HIV to experience social disruptions (51.1% vs. 39.8%, P < 0.001). Participants who experienced ≥2 social disruptions had significantly higher odds of depression symptoms [aOR = 1.32; 95% confidence interval (CI): 1.12 to 1.56], anxiety (aOR = 1.63; 95% CI: 1.17 to 2.27), and social support dissatisfaction (aOR = 1.81; 95% CI: 1.26 to 2.60).ConclusionsThis study builds on emerging literature demonstrating the psychosocial health impact related to the COVID-19 pandemic by providing context specific to PLHIV. The ongoing pandemic requires structural and social interventions to decrease social disruption and address psychosocial health needs among the most vulnerable populations.

BackgroundNovel 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.MethodsWe 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.ResultsOf 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 β2-microglobulin [β2m]), and higher YKL-40, whereas HIV viremia was associated with worsening markers of tubular and glomerular injury (higher KIM-1 and albuminuria, respectively).ConclusionsCKD 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.

Stigma in health care settings can have negative consequences on women living with HIV, such as increasing the likelihood of missed visits and reducing trust in their clinical providers. Informed by prior stigma research and considering knowledge gaps related to the effect of patient-provider race concordance, we conducted this study to assess if patient-provider race concordance moderates the expected association between HIV-related stigma in health care settings and patients' trust in their providers. Moderation analyses were conducted using Women's Interagency HIV Study data (N = 931). We found significant main effects for patient-provider race concordance. Higher experienced stigma was associated with lower trust in providers in all patient-provider race combinations [White-White: B = -0.89, standard error (SE) = 0.14, p = 0.000, 95% confidence interval, CI (-1.161 to -0.624); Black patient-White provider: B = -0.19, SE = 0.06, p = 0.003, 95% CI (-0.309 to -0.062); and Black-Black: B = -0.30, SE = 0.14, p = 0.037, 95% CI (-0.575 to -0.017)]. Higher anticipated stigma was also associated with lower trust in providers [White-White: B = -0.42, SE = 0.07, p = 0.000, 95% CI (-0.552 to -0.289); Black patient-White provider: B = -0.17, SE = 0.03, p = 0.000, 95% CI (-0.232 to -0.106); and Black-Black: B = -0.18, SE = 0.06, p = 0.002, 95% CI (-0.293 to -0.066)]. Significant interaction effects indicated that the negative associations between experienced and anticipated HIV-related stigma and trust in providers were stronger for the White-White combination compared with the others. Thus, we found that significant relationships between HIV-related experienced and anticipated stigma in health care settings and trust in providers exist and that these associations vary across different patient-provider race combinations. Given that reduced trust in providers is associated with antiretroviral medication nonadherence and higher rates of missed clinical visits, interventions to address HIV-related stigma in health care settings may improve continuum of care outcomes.

Background: The syndemic of HIV, substance use (SU), and mental illness has serious implications for HIV disease progression among women. We described co-utilization of HIV care, SU treatment, and mental health treatment among women with or at risk for HIV. Methods: We included data from women with or at risk for HIV (n = 2559) enrolled in all 10 sites of the Women's Interagency HIV Study (WIHS) from 2013 to 2020. Current SU was defined as self-reported, non-medical use of drugs in the past year, excluding use of only marijuana. Tobacco and alcohol were assessed separately. We described co-utilization of SU treatment, tobacco and alcohol use treatment, HIV care, and mental health care in the past year among women who were eligible for each service. We compared service utilization by those who did/did not utilize SU treatment using Wald Chi-square tests. Results: Among women with current SU (n = 358), 42% reported utilizing SU treatment. Among those with current SU+HIV (n = 224), 84% saw their HIV provider, and 34% saw a mental health provider. Among women with current SU+heavy alcohol use (n = 95), 18% utilized alcohol use treatment; among current SU+tobacco use (n = 276), 8% utilized tobacco use treatment. Women who utilized SU treatment had higher utilization of alcohol use treatment (59% vs. 5%; P <.001) and tobacco use treatment (12% vs. 5%; P =.028). HIV care engagement was high regardless of SU treatment. Conclusions: We found high engagement in SU and HIV care, but low engagement in alcohol and tobacco use treatment. Integrated SU treatment services for women, including tobacco/alcohol treatment and harm reduction, are needed to optimize treatment engagement and HIV care continuum outcomes. [ABSTRACT FROM AUTHOR]

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. Author summary: The host epigenome (i.e., the DNA methylome) plays a pivotal role in HIV-1 viral integration, maintenance, and activation or silencing. Epigenome-wide association studies have identified many DNA methylation CpG sites in bulk cells associated with HIV infection, which offer an aggregated view of the average DNA methylation across cell types. To understand the effect of DNA methylation on chronic HIV infection at the cell-type level, we applied a computational method to deconvolute DNA methylation from blood bulk cells into five cell types: CD4+ T cell, CD8+ T cell, B cell, Nature Killer cell, and Monocytes and conducted an epigenome-wide analysis for HIV infection in each inferred cell type. Our results show that most of the HIV infection associated CpG sites are unique to each cell type. The largest number of significant CpG sites for HIV infection are from inferred CD4+ T cells. Significant CpG sites are located on genes that are enriched in interferon-α and -γ pathways, which are known to be key players in HIV infection. The findings help us understand the cellular relationship between DNA methylation and HIV infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]