Interagency Human Immunodeficiency Virus Study Research Articles

Examining the relationships between pain symptoms and psychosocial functioning among women living with and at risk for human immunodeficiency virus using a cross-sectional psychological network analysis.

Pain is prevalent among women living with HIV (WLWH); however, research on pain experience among WLWH in the United States is limited. This study used a network analysis to simultaneously examine the relationships between pain experience and psychosocial functioning among WLWH and human immunodeficiency virus (HIV)-negative women. A secondary analysis of public data from the Women's Interagency HIV Study, a U.S. longitudinal cohort study of the experiences of WLWH and women at increased risk for HIV (HIV negative), was completed. Data were from Visit 42 in 2015 and included 451 WLWH and 194 HIV-negative women who endorsed experiencing pain in the week prior to the interview. Similar to the sociodemographic characteristics of WLWH in the United States, the majority of women in the sample were racially and/or ethnically minoritized and of low socioeconomic position. Networks were modeled using measures of pain intensity, pain interference, depression symptoms, anxiety/worry symptoms, meaning in life, and emotional support. Network models for WLWH and HIV-negative women were comparable (ps > .05). Depression symptoms were a central construct (strength = 1.82 and 1.77, respectively) within the networks, and pain interference was associated with psychosocial constructs (ps < .05), while pain intensity was not (ps > .05). Meaning in life and emotional support were not directly associated with pain (ps > .05). Network findings suggest that reducing depression symptoms may result in improved pain experience and broader positive impact for WLWH and for women at increased risk of HIV. This finding is consistent with research with other pain-focused populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Intact HIV Reservoir in Monocytes Is Associated With Cognitive Function in Virally Suppressed Women With HIV

Abstract Background Monocytes are susceptible to human immunodeficiency virus (HIV) infection, form HIV reservoirs, and contribute to central nervous system complications (eg, cognitive impairment) in virally suppressed women with HIV (vsWWH). However, it remains unknown if the quality and/or quantity of the monocyte reservoir contributes to cognition in vsWWH. Methods Sixty-two vsWWH (mean age = 56.1 years, SD = 7.1; 93% Black, non-Hispanic; all HIV RNA &amp;lt;250 copies/mL) completed a cognitive test battery, blood draw, and whole-blood immunophenotyping. Monocytes and CD4 T cells were isolated from a subset of 53 participants and the HIV reservoir was assessed using cell-specific intact proviral DNA assays (IPDA). Demographically adjusted z-scores were calculated for each outcome using data from participants without HIV in the Women's Interagency HIV Study. Cognitive outcomes of interest included domain-specific and global z-scores. Results Thirty-Eight percent of vsWWH had detectable intact HIV genomes in monocytes (median = 21.5 copies/million). Higher levels of intact HIV genomes per million monocytes were associated with poorer verbal memory (delayed recall, r = 0.55, P = .01; recognition, r = 0.46, P = .04), fine motor skills (r = 0.50, P = .03), and global function (r = 0.47, P = .04). Higher levels of intact HIV genomes in monocytes were associated with percent intermediate monocytes (r = 0.60, P = .008), and the ratio of intact per intermediate monocyte was associated with worse memory (r = −0.59, P = .008). There were no associations between CD4 reservoir and cognition. Conclusions The number of intact HIV genomes per million monocytes was related to poorer cognition and the percentage of intermediate monocytes. These findings suggest that the presence of HIV genomes in general do not relate to cognitive complications, but intact, and therefore potentially replication-competent HIV, may contribute to cognitive complications in vsWWH.

HIV, HIV-Specific Factors, and Myocardial Disease in Women.

People with human immunodeficiency virus (HIV) (PWH) have an increased risk of cardiovascular disease (CVD). Cardiac magnetic resonance (CMR) has documented higher myocardial fibrosis, inflammation, and steatosis in PWH, but studies have mostly relied on healthy volunteers as comparators and focused on men. We investigated the associations of HIV and HIV-specific factors with CMR phenotypes in female participants enrolled in the Women's Interagency HIV Study's New York and San Francisco sites. Primary phenotypes included myocardial native (n) T1 (fibro-inflammation), extracellular volume fraction (fibrosis), and triglyceride content (steatosis). Associations were evaluated with multivariable linear regression, and results pooled or meta-analyzed across centers. Among 261 women with HIV (WWH, N = 362), 76.2% had undetectable viremia at CMR. For the 82.8% receiving continuous antiretroviral therapy (ART) in the preceding 5 years, adherence was 51.7%, and 69.4% failed to achieve persistent viral suppression (40.7% with peak viral load <200 cp/mL). Overall, WWH showed higher nT1 than women without HIV after full adjustment. This higher nT1 was more pronounced in those with antecedent or current viremia or nadir CD4+ count <200 cells/μL, with the latter also associated with higher extracellular volume fraction. WWH and current CD4+ count <200 cells/μL had less cardiomyocyte steatosis. Cumulative exposure to specific ART showed no associations. Compared with sociodemographically similar women without HIV, WWH on ART exhibit higher myocardial fibro-inflammation, which is more prominent with unsuppressed viremia or CD4+ lymphopenia. These findings support the importance of improved ART adherence strategies, along with better understanding of latent infection, to mitigate cardiac end-organ damage in this population.

Health Insurance and Initiation of Direct-Acting Antivirals for Hepatitis C in US Women With Human Immunodeficiency Virus.

Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) is well tolerated, cost-effective, and yields high sustained virologic response rates, yet it has remained financially inaccessible to many patients. Participants of the Women's Interagency HIV Study (an observational US cohort) with human immunodeficiency virus (HIV) and HCV (RNA+) reporting no prior hepatitis C treatment were followed for DAA initiation (2015-2019). We estimated risk ratios (RRs) of the relationship between time-varying health insurance status and DAA initiation, adjusting for confounders with stabilized inverse probability weights. We also estimated weighted cumulative incidences of DAA initiation by health insurance status. A total of 139 women (74% Black) were included; at baseline, the median age was 55 years and 86% were insured. Most had annual household incomes ≤$18 000 (85%); advanced liver fibrosis (21%), alcohol use (45%), and recreational drug use (35%) were common. Across 439 subsequent semiannual visits, 88 women (63%) reported DAA initiation. Compared with no health insurance, health insurance increased the likelihood of reporting DAA initiation at a given visit (RR, 4.94; 95% confidence limit [CL], 1.92 to 12.8). At 2 years, the weighted cumulative incidence of DAA initiation was higher among the insured (51.2%; 95% CL, 43.3% to 60.6%) than the uninsured (3.5%; 95% CL, 0.8% to 14.6%). Accounting for clinical, behavioral, and sociodemographic factors over time, health insurance had a substantial positive effect on DAA initiation. Interventions to increase insurance coverage should be prioritized to increase HCV curative therapy uptake for persons with HIV.

Substance Use Treatment Utilization Among Women With and Without Human Immunodeficiency Virus.

Substance 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). We 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. Among 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. Treatment 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.

Human Immunodeficiency Virus and Cardiac End-Organ Damage in Women: Findings From an Echocardiographic Study Across the United States.

People with human immunodeficiency virus (HIV) have been reported to have increased risk of clinical and subclinical cardiovascular disease. Existing studies have focused on men and often have been uncontrolled or lacked adequate HIV-negative comparators. We performed echocardiography in the Women's Interagency HIV Study to investigate associations of HIV and HIV-specific factors with cardiac phenotypes, including left ventricular systolic dysfunction (LVSD), isolated LV diastolic dysfunction (LVDD), left atrial enlargement (LAE), LV hypertrophy (LVH), and increased tricuspid regurgitation velocity (TRV). Of 1654 participants (age 51 ± 9 years), 70% had HIV. Sixty-three (5.4%) women with HIV (WWH) had LVSD; 71 (6.5%) had isolated LVDD. Compared with women without HIV (WWOH), WWH had a near-significantly increased risk of LVSD (adjusted relative risk = 1.69; 95% confidence interval = 1.00 to 2.86; P = .051). No significant association was noted for HIV seropositivity with other phenotypes, but there was a risk gradient for decreasing CD4+ count among WWH that approached or reached significance for isolated LVDD, LAE, and LVH. WWH with CD4+ count <200 cells/mm3 had significantly higher prevalence of LAE, LVH, and high TRV than WWOH. There were no consistent associations for viral suppression or antiretroviral drug exposure. This study suggests that WWH have a higher risk of LVSD compared with sociodemographically similar WWOH, but their risk for isolated LVDD, LAE, LVH, and high TRV is increased only with reduced CD4+ count. Although these findings warrant replication, they support the importance of cardiovascular risk-factor and HIV-disease control for heart disease prevention in this population.

Glucocorticoid Receptor Function and Cognitive Performance in Women With HIV.

ABSTRACTObjectiveAlterations in glucocorticoid receptor (GCR) function may be a risk factor for cognitive complications among older people with human immunodeficiency virus (HIV). We evaluated whether HIV serostatus and age modify the GCR function-cognition association among women.MethodsEighty women with HIV (n = 40, <40 years of age [younger]; n = 40, >50 years of age [older]) and 80 HIV-uninfected women (n = 40 older, n = 40 younger) enrolled in the Women’s Interagency HIV Study completed a comprehensive neuropsychological test battery. Peripheral blood mononuclear cells collected concurrent with neuropsychological testing were assessed for GCR function. Multivariable linear regression analyses were conducted to examine whether a) HIV serostatus and age were associated with GCR function, and b) GCR function-cognition associations are moderated by HIV serostatus and age adjusting for relevant covariates.ResultsAmong older women, higher baseline FKBP5 expression level was associated with lower attention/working memory performance among women with HIV (B = 6.4, standard error = 1.7, p = .0003) but not in women without HIV infection (B = −1.7, standard error = 1.9, p = .37). There were no significant HIV serostatus by age interactions on dexamethasone (DEX)-stimulated expression of the genes regulated by the GCR or lipopolysaccharide-stimulated tumor necrosis factor α levels (with or without DEX stimulation; p values > .13). HIV serostatus was associated with GC target genes PER1 (p = .006) and DUSP1 (p = .02), but not TSC22D3 (p = .32), after DEX stimulation.ConclusionsCollectively, these data suggest that HIV serostatus and age may modify the influence of the GCR, such that the receptor is likely engaged to a similar extent, but the downstream influence of the receptor is altered, potentially through epigenetic modification of target genes.

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

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. 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. 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. 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.

Class-Based Antiretroviral Exposure and Cognition Among Women Living with HIV.

Neurologic complications of the human immunodeficiency virus (HIV) are common in treated individuals, and toxicity of certain antiretroviral therapies (ART) may contribute to cognitive impairment. We investigated exposures to specific ART and cognition among women living with HIV (WLWH). Virologically suppressed (viral load <200 copies/mL during at least two semi-annual visits) WLWH and age/race matched HIV-seronegative controls enrolled in the Women's Interagency HIV Study who completed at least two biennial cognitive assessments were included. Analysis of WLWH was restricted to those with exposure to the drug class of interest and a nucleoside reverse transcriptase inhibitor (NRTI) backbone. Generalized estimating equations were used to evaluate repeated measures of cognition over time in association with ART class exposure. Among 1,242 eligible WLWH, 20% (n = 247) had isolated drug exposure to non-nucleoside reverse transcriptase inhibitors (NNRTI), 18% (n = 219) to protease inhibitors (PIs), and 6% (n = 79) to integrase inhibitors with a NRTI backbone. Cognitive assessments were performed at a median of 3 biennial visits {IQR 2-4 visits}. At the index assessment, 21% of WLWH demonstrated global cognitive impairment versus 29% at their last cognitive assessment. In multivariable analyses adjusted for hypertension, depression, diabetes mellitus, history of AIDS-defining illness, alcohol use, number of medications, and time on ART, WLWH exposed to NNRTIs demonstrated verbal learning improvements (mean T-score change 1.3, p = .020) compared to other treated women. Compared to HIV-seronegative women, WLWH exposed to PIs had worse verbal learning (mean T-score difference -2.62, p = .002) and verbal memory performance (mean T-score difference -1.74, p = .032) at baseline. Compared to HIV-seronegative women, WLWH exposed to PIs had improvements in verbal learning (mean T-score slope difference 0.36, p = .025) and verbal memory (mean T-score slope difference 0.32, p = .042). The index T-score and slope of change in the T-score were similar among other treated groups and the HIV-seronegative group. We noted emerging trends in cognition in WLWH exposed to specific drug classes. Ongoing study of this relatively young group is important to characterize long-term cognitive outcomes and effect of antiretrovirals as treatment guidelines evolve.

Human Immunodeficiency Virus (HIV) and Menopause Are Independently Associated With Lower Bone Mineral Density: Results From the Women's Interagency HIV Study.

We previously reported lower bone mineral density (BMD) among premenopausal women with HIV (WWH) compared to women without HIV (HIV-). Rate of bone loss may be even greater for WWH during the menopausal transition. Pre-, peri- and postmenopausal women in the Women\'s Interagency HIV Study (WIHS) underwent whole body DXA and central quantitative computed tomography to measure areal BMD (aBMD) and volumetric BMD (vBMD), respectively. Multivariable regression models with covariates associated with low aBMD (T score < -1.0) in univariate analyses (P≤.05) and known risk factors for low BMD assessed contributions of HIV and menopausal stage to the prediction of aBMD. Compared to HIV- women, in unadjusted analyses, WWH had 5-9% lower aBMD at the lumbar spine (P=.001), femoral neck (P=.04), total hip (P=.003) and the ultradistal radius (P=.004), and higher osteoporosis prevalence (T score<-2.5) at the ultradistal radius only (13.5% vs 0%, P=.0003). WWH also had lower vBMD at the spine and hip. In fully adjusted models, HIV independently predicted reduced aBMD at the lumbar spine, total hip, femoral neck, and ultradistal radius; menopausal stage remained a significant predictor of lumbar spine and ultradistal radius aBMD. HIV infection and menopausal stage were independent predictors of lower BMD, and had an additive effect on lumbar spine and total hip BMD. Additional research is needed to better understand underlying mechanisms by which HIV impacts BMD as women age and transition through menopause, and develop strategies to mitigate osteoporosis and fracture risk in this growing population.

T-Cell Immune Dysregulation and Mortality in Women With Human Immunodeficiency Virus.

In women with HIV, higher activation and exhaustion of CD4+ T cells were associated with risk of non-HIV-related mortality during a median of 13.3 years of follow-up, independent of baseline demographic, behavioral, HIV-related, and cardiometabolic factors and longitudinal HIV disease progression. Dysregulation of adaptive immunity is a hallmark of human immunodeficiency virus (HIV) infection that persists on antiretroviral therapy (ART). Few long-term prospective studies have related adaptive immunity impairments to mortality in HIV, particularly in women. Among 606 women with HIV in the Women's Interagency HIV Study, peripheral blood mononuclear cells collected from 2002 to 2005 underwent multiparameter flow cytometry. Underlying cause of death was ascertained from the National Death Index up to 2018. We examined associations of CD4+ and CD8+ T-cell activation (%CD38+HLA-DR+), senescence (%CD57+CD28-), exhaustion (%PD-1+), and nonactivation/normal function (%CD57-CD28+) with natural-cause, HIV-related, and non-HIV-related mortality. At baseline, median participant age was 41, and 67% were on ART. Among 100 deaths during a median of 13.3 years follow-up, 90 were natural-cause (53 non-HIV-related, 37 HIV-related). Higher activation and exhaustion of CD4+ T cells were associated with risk of natural-cause and non-HIV-related mortality, adjusting for age, demographic, behavioral, HIV-related, and cardiometabolic factors at baseline. Additional adjustment for time-varying viral load and CD4+ T-cell count did not attenuate these associations. CD8+ T-cell markers were not associated with any outcomes adjusting for baseline factors. Persistent CD4+ T-cell activation and exhaustion may contribute to excess long-term mortality risk in women with HIV, independent of HIV disease progression.

Trends in Bacterial Vaginosis Prevalence in a Cohort of U.S. Women with and at Risk for HIV.

Background: Women with human immunodeficiency virus (HIV) often have bacterial vaginosis (BV). The goal of this analysis was to assess how BV prevalence changed over time and across U.S. regions in enrollment cohorts of the Women's Interagency HIV Study. Methods: In a multisite study, BV was diagnosed retrospectively when pH and two of three other Amsel criteria were met. Prevalence was determined across four recruitment waves: 1994-5, 2001-2, 2011-2, and 2013-5. Generalized estimating equation multivariable logistic regression models assessed changes in visit prevalence across waves after controlling for HIV disease severity and other risks. Results: Among 4,790 women (3,539 with HIV and 1,251 without HIV), BV was diagnosed at 7,870 (12%) of 64,444 visits. Baseline prevalence across enrollment waves was 15.0%-19.2%, but declined in all cohorts, with prevalence in the initial cohort falling to 3.9% in the 1994-5 cohort after up to 21 years of continuous observation. Prevalence varied within U.S. regions. HIV status was not associated with BV. Conclusion: BV prevalence decreased with time in study. Prevalence varied across sites, but was not uniformly increased or decreased in any U.S. region. Clinical Trials.gov identifier: NCT00000797.

A Bayesian nonparametric approach for inferring drug combination effects on mental health in people with HIV.

Although combination antiretroviral therapy (ART) with three or more drugs is highly effective in suppressing viral load for people with HIV (human immunodeficiency virus), many ART agents may exacerbate mental health-related adverse effects including depression. Therefore, understanding the effects of combination ART on mental health can help clinicians personalize medicine with less adverse effects to avoid undesirable health outcomes. The emergence of electronic health records offers researchers' unprecedented access to HIV data including individuals' mental health records, drug prescriptions, and clinical information over time. However, modeling such data is challenging due to high dimensionality of the drug combination space, the individual heterogeneity, and sparseness of the observed drug combinations. To address these challenges, we develop a Bayesian nonparametric approach to learn drug combination effect on mental health in people with HIV adjusting for sociodemographic, behavioral, and clinical factors. The proposed method is built upon the subset-tree kernel that represents drug combinations in a way that synthesizes known regimen structure into a single mathematical representation. It also utilizes a distance-dependent Chinese restaurant process to cluster heterogeneous populations while considering individuals' treatment histories. We evaluate the proposed approach through simulation studies, and apply the method to a dataset from the Women's Interagency HIV Study, showing the clinical utility of our model in guiding clinicians to prescribe informed and effective personalized treatment based on individuals' treatment histories and clinicalcharacteristics.

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.

Perceived Neighborhood-Level Drivers of Food Insecurity Among Aging Women in the United States: A Qualitative Study

BackgroundAging populations in the United States exhibit high rates of food insecurity and chronic illness. Few studies have explored the neighborhood-level drivers of food insecurity among such populations, and how they intersect with experiences of aging. ObjectiveThe aim of this study was to explore how aging women experience food insecurity in the United States, and the neighborhood-level factors that influence these experiences. DesignSemistructured qualitative interviews were conducted to elicit participants’ perceptions of how their neighborhood influenced their experiences with food security and aging. Participants/settingThirty-eight food-insecure women aged 50 years and older were purposively sampled from the Northern California, Georgia, and North Carolina sites of the Women’s Interagency Human Immunodeficiency Virus Study. Interviews were conducted between November 2017 and July 2018 at the three Women’s Interagency Human Immunodeficiency Virus Study sites. Statistical analysisThree researchers thematically analyzed the data using an inductive–deductive approach. ResultsParticipants described neighborhood-level drivers of food insecurity that centered around three themes: accessibility of food from traditional food stores, the role of food aid institutions, and the intersection of aging with the food environment. Participants explained that food insecurity was related to limited access to food stores largely due to long distances and poor public transportation in Georgia and North Carolina, and high food prices in Northern California. Most participants described being dependent on food aid programs, but found this difficult due to poor quality food and long wait times. Aging-related issues emerged as a cross-cutting theme, with fatigue, poor strength, and chronic illness amplifying barriers to accessing food. ConclusionsFindings from this study reveal the structural barriers that aging women face in accessing healthy food within their neighborhoods, and how experiences with aging and chronic illnesses exacerbate these barriers. Although future programs should address common neighborhood-level barriers such as the accessibility and affordability of healthy foods, they should also be tailored to aging women and the local context.

Incident Non-AIDS Comorbidity Burden Among Women With or at Risk for Human Immunodeficiency Virus in the United States.

Human immunodeficiency virus (HIV) infection may accelerate development of aging-related non-AIDS comorbidities (NACMs). The incidence of NACMs is poorly characterized among women living with HIV (WLWH). WLWH and HIV-seronegative participants followed in the Women's Interagency HIV Study (WIHS) through 2009 (when >80% of WLWH used antiretroviral therapy) or onward were included, with outcomes measured through 31 March 2018. Sociodemographics, clinical covariates, and prevalent NACM were determined at enrollment. We used Poisson regression models to determine incident NACM burden (number of NACMs accrued through most recent WIHS visit out of 10 total NACMs assessed) by HIV serostatus and age. There were 3129 participants (2239 WLWH, 890 HIV seronegative) with 36 589 person-years of follow-up. At enrollment, median age was 37 years, 65% were black, and 47% currently smoked. In fully adjusted analyses, WLWH had a higher incident NACM rate compared with HIV-seronegative women (incidence rate ratio, 1.36 [95% confidence interval (CI), 1.02-1.81]). Incident NACM burden was higher among WLWH vs HIV-seronegative women in most age strata (HIV × age interaction: P = .0438), and women <25 years old had the greatest incidence rate ratio by HIV serostatus at 1.48 (95% CI, 1.19-1.84) compared with those in older age groups. Incident NACM burden was associated with traditional comorbidity risk factors but not HIV-specific indices. Incident NACM burden was higher among WLWH than HIV-seronegative women. This difference was most dramatic among women aged <25 years, a group for whom routine comorbidity screening is not prioritized. Established non-HIV comorbidity risk factors were significantly associated with incident NACM burden. More data are needed to inform best practices for NACM screening, prevention, and management among WLWH, particularly young women.

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

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. 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. 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. 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.

Cutaneous microvessel circulation and vasomotion responses to local skin heating in women with HIV.

BackgroundPatients infected with the human immunodeficiency virus (HIV) who are well treated by ART still suffer from many complications of microvascular dysfunction. Our previous ex vivo study reported that subcutaneous microvessels from women living with HIV had severe endothelial dysfunction. However, it is unknown whether the microvascular defect is more widespread. We tested the hypothesis that microvascular endothelial, neural and myogenic functions are impaired in women living with HIV compared to control women (control).MethodsWomen with HIV (n = 35) were compared to matched controls (n = 24). HIV infection was virally suppressed on antiretroviral therapy and both groups were enrolled in the DC Women’s Interagency HIV Study (DC – WIHS). Cutaneous blood flow (CBF) was measured by laser Doppler flowmetry (LDF) during an increase of local skin temperature from 33°C to 42°C. Vasomotion responses were analyzed using a wavelet transform to calculate the power of the frequency intervals associated with endothelial (0.0095 ‐0.012Hz), neural (0.021‐0.05Hz) and myogenic (0.051 ‐0.15Hz) activities of the Laser‐Doppler signal. Data are present as mean ± SEM.ResultCBF was increased in both groups with LH at 42°C, but the increases of CBF to heat was lower in HIV infected women than controls (13.9 ± 1.1 vs 15.6 ± 1.2 fold, p&lt;0.05). Vasomotion activities were similar between groups at baseline (33°C) and increased in both groups with LH at 42°C, but the increase was less in HIV compared to controls (13.9 ± 1.1 vs 15.6 ± 1.2 fold change, P &lt;0.05). Moreover, compared to the control group, HIV had lower wavelet amplitude during LH in endothelial (100±3.8 vs 149± 15 PU/Hz/min, P&lt;0.05), neural (92 ± 5 vs 132 ±15 PU/Hz/min, P&lt;0.05) and myogenic (46±3 vs 60 ±7 PU/Hz/min, P=NS) frequency intervals.ConclusionWomen living with HIV have impaired microvascular dysfunction with a complex derangement of microvascular circulatory regulation involving the endothelial, neural and myogenic components. Thus, fully preventing microvascular disease in HIV will require correction of widespread microvascular defects.Support or Funding InformationNational Heart, Lung, and Blood Institute (NHLBI), R01 HL134511

The Changing Science of HIV Epidemiology in the United States.

In 1984, a large prospective study of the natural history of human immunodeficiency virus (HIV) infection, the Multicenter AIDS Cohort Study (MACS), was established; 10 years later, the Women’s Interagency HIV Study (WIHS) was launched. Motivated by the merger and redesign of these long-standing HIV cohort studies in 2019, we review ways in which HIV epidemiology in the United States has transformed over the lives of these studies and how this evolution has influenced planning for enrollment and follow-up. We highlight changes that have occurred in the 3 major domains that are central to epidemiologic science: changes to key populations at highest risk for HIV, refinements in measurement and shifts in the outcomes of interest, and a new era in the tools and approaches that epidemiologists use to synthesize evidence from measurements made on populations. By embracing foundational principles with modern methods, the epidemiologic approach of analyzing the causes and distributions of diseases in contemporaneous populations will continue to advance HIV science over the next decade.

Weight Gain Associated With Integrase Stand Transfer Inhibitor Use in Women.

Integrase strand-transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is recommended for human immunodeficiency virus (HIV) management. Although studies have suggested associations between INSTIs and weight gain, women living with HIV (WLHIV) have been underrepresented in research. We evaluated the effect of switching or adding INSTIs among WLHIV. Women enrolled in the Women's Interagency HIV Study (WIHS) from 2006-2017 who switched to or added an INSTI to ART (SWAD group) were compared to women on non-INSTI ART (STAY group). Body weight, body mass index (BMI), percentage body fat (PBF), and waist, hip, arm, and thigh circumferences were measured 6-12 months before and 6-18 months after the INSTI switch/add in SWAD participants, with comparable measurement time points in STAY participants. Linear regression models compared changes over time by SWAD/STAY group, adjusted for age, race, WIHS site, education, income, smoking status, and baseline ART regimen. We followed 1118 women (234 SWAD and 884 STAY) for a mean of 2.0 years (+/- 0.1 standard deviation [SD]; mean age 48.8 years, SD +/- 8.8); 61% were Black. On average, compared to the STAY group, the SWAD group experienced mean greater increases of 2.1 kg in body weight, 0.8 kg/m2 in BMI, 1.4% in PBF, and 2.0, 1.9, 0.6, and 1.0 cm in waist, hip, arm, and thigh circumference, respectively (all P values < .05). No differences in magnitudes of these changes were observed by INSTI type. In WLHIV, a switch to INSTI was associated with significant increases in body weight, body circumferences, and fat percentages, compared to non-INSTI ART. The metabolic and other health effects of these changes deserve further investigation.