Microbial Translocation and Gut Damage Are Associated With an Elevated Fast Score in Women Living With and Without HIV.

Background: Steatohepatitis is common in persons living with HIV and may be associated with gut microbial translocation (MT). However, few studies have evaluated the gut-liver axis in persons living with HIV. In the Women's Interagency HIV Study, we examined the associations of HIV and circulating biomarkers linked to MT and gut damage using the FibroScan-aspartate aminotransferase (FAST) score, a noninvasive surrogate for steatohepatitis with advanced fibrosis. Methods: Among 883 women with HIV and 354 without HIV, we used multivariable regression to examine the associations of HIV and serum biomarkers linked to MT and gut damage (kynurenine and tryptophan ratio, intestinal fatty acid-binding protein, soluble CD14, and soluble CD163) with a log-transformed FAST score after adjusting for key covariates. We used a path analysis and mediation models to determine the mediating effect of each biomarker on the association of HIV with FAST. Results: HIV infection was associated with a 49% higher FAST score. MT biomarker levels were higher in women with HIV than women without HIV (P < .001 for each). MT biomarkers mediated 13% to 32% of the association of HIV and FAST score. Conclusions: Biomarkers linked to MT and gut damage are associated with a higher FAST score and mediate the association of HIV with a higher FAST score. Our findings suggest that MT may be an important mechanism by which HIV increases the risk of steatohepatitis with advanced fibrosis.

Microfluidic Isolation of Neuronal-Enriched Extracellular Vesicles Shows Distinct and Common Neurological Proteins in Long COVID, HIV Infection and Alzheimer's Disease.

Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning of the COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people with LongC contained proteins associated with Alzheimer's disease (AD). Since that time, a subset of people with prior COVID infection continue to report neurological problems more than three months after infection. Blood markers to better characterize LongC are elusive. To further identify neuronal proteins associated with LongC, we maximized the number of nEVs isolated from plasma by developing a hybrid EV Microfluidic Affinity Purification (EV-MAP) technique. We isolated nEVs from people with LongC and neurological complaints, AD, and HIV infection with mild cognitive impairment. Using the OLINK platform that assesses 384 neurological proteins, we identified 11 significant proteins increased in LongC and 2 decreased (BST1, GGT1). Fourteen proteins were increased in AD and forty proteins associated with HIV cognitive impairment were elevated with one decreased (IVD). One common protein (BST1) was decreased in LongC and increased in HIV. Six proteins (MIF, ENO1, MESD, NUDT5, TNFSF14 and FYB1) were expressed in both LongC and AD and no proteins were common to HIV and AD. This study begins to identify differences and similarities in the neuronal response to LongC versus AD and HIV infection.

Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection.

People living with HIV (PLWH) experience increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors associated with this vulnerability remain uncertain. In the general population, alterations in the N-glycans on IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG N-glycans in cross-sectional and longitudinal samples from 1214 women and men, living with and without HIV. PLWH exhibit an accelerated accumulation of pro-aging-associated glycan alterations and heightened expression of senescence-associated glycan-degrading enzymes compared to controls. These alterations correlate with elevated markers of inflammation and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit a reduced ability to elicit anti-HIV Fc-mediated immune activities. These findings hold potential for the development of biomarkers and tools to identify and prevent premature aging and comorbidities in PLWH.

Declining Prevalence of Trichomonas vaginalis Diagnosed by Wet Mount in a Cohort of U.S. Women With and Without HIV.

Background: Women living with HIV (WLWH) are often coinfected with Trichomonas vaginalis (TV), and annual screening is recommended. Our goal was to assess differences in TV prevalence at study entry and over time in enrollment cohorts of the Women's Interagency HIV Study. Methods: In a multisite study, TV was diagnosed by wet mount microscopy. Prevalence was determined across four enrollment waves: 1994-1995, 2001-2002, 2011-2012, and 2013-2015. Generalized estimating equation multivariable logistic regression models assessed changes in visit prevalence across waves after controlling for HIV disease severity and other risks. Results: At 63,824 person-visits (3,508 WLWH and 1,262 women without HIV), TV was diagnosed by wet mount at 1979 visits (3.1%). After multivariable adjustment, HIV status was not associated with TV detection, which was more common among younger women, women with multiple partners, and irregular condom use. All enrollment waves showed a decline in TV detection over time, although p-value for trend did not reach significance for most recent waves. To explore the potential utility of screening among WLWH, we assessed rates of TV detection among women without appreciable vaginal discharge on examination. Initial TV prevalence among asymptomatic women was 3.5%, and prevalence decreased to 0.5%-1% in the most recent wave (2013-2015) (p-trend <0.0001). Conclusions: In this cohort, TV rates are low among WLWH, and HIV does not increase TV risk. Screening may benefit newly diagnosed WLWH, women with risk factors, or those receiving care sporadically but is unlikely to further reduce the low rate of TV among women in care, especially older women without multiple partners. The clinical trials registration number for WIHS is NCT00000797.

The replication-competent HIV reservoir is a genetically restricted, younger subset of the overall pool of HIV proviruses persisting during therapy, which is highly genetically stable over time.

Within-host HIV populations continually diversify during untreated infection, and this diversity persists within infected cell reservoirs during antiretroviral therapy (ART). Achieving a better understanding of on-ART proviral evolutionary dynamics, and a better appreciation of how the overall persisting pool of (largely genetically defective) proviruses differs from the much smaller replication-competent HIV reservoir, is critical to HIV cure efforts. We reconstructed within-host HIV evolutionary histories in blood from seven participants of the Women's Interagency HIV Study who experienced HIV seroconversion, and used these data to characterize the diversity, lineage origins, and ages of proviral env-gp120 sequences sampled longitudinally up to 12 years on ART. We also studied HIV sequences emerging from the reservoir in two participants. We observed that proviral clonality generally increased over time on ART, with clones frequently persisting long term. While on-ART proviral integration dates generally spanned the duration of untreated infection, HIV emerging in plasma was exclusively younger (i.e., dated to the years immediately pre-ART). The genetic and age distributions of distinct proviral sequences remained stable during ART in all but one participant, in whom there was evidence that younger proviruses had been preferentially eliminated after 12 years on ART. Analysis of the gag region in three participants corroborated our env-gp120-based observations, indicating that our observations are not influenced by the HIV region studied. Our results underscore the remarkable genetic stability of the distinct proviral sequences that persist in blood during ART. Our results also suggest that the replication-competent HIV reservoir is a genetically restricted, younger subset of this overall proviral pool.IMPORTANCECharacterizing the genetically diverse HIV sequences that persist in the reservoir despite antiretroviral therapy (ART) is critical to cure efforts. Our observations confirm that proviruses persisting in blood on ART, which are largely genetically defective, broadly reflect the extent of within-host HIV evolution pre-ART. Moreover, on-ART clonal expansion is not appreciably accompanied by the loss of distinct proviral lineages. In fact, on-ART proviral genetic composition remained stable in all but one participant, in whom, after 12 years on ART, proviruses dating to around near ART initiation had been preferentially eliminated. We also identified recombinant proviruses between parental sequence fragments of different ages. Though rare, such sequences suggest that reservoir cells can be superinfected with HIV from another infection era. Overall, our finding that the replication-competent reservoir in blood is a genetically restricted, younger subset of all persisting proviruses suggests that HIV cure strategies will need to eliminate a reservoir that differs in key respects from the overall proviral pool.

Disparities in Hypertension Prevalence, Awareness, Treatment, and Control Among Women Living With and Without HIV in the US South.

Background: Hypertension-related diseases are major causes of morbidity among women living with HIV. We evaluated cross-sectional associations of race/ethnicity and HIV infection with hypertension prevalence, awareness, treatment, and control. Methods: Among women recruited into Southern sites of the Women's Interagency HIV Study (2013-2015), hypertension was defined as (1) systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg according to clinical guidelines when data were collected, (2) self-report of hypertension, or (3) use of antihypertensive medication. Awareness was defined as self-report of hypertension, and treatment was self-report of any antihypertensive medication use. Blood pressure control was defined as <140/90 mm Hg at baseline. Prevalence ratios for each hypertension outcome were estimated through Poisson regression models with robust variance estimators adjusted for sociodemographic, behavioral, and clinical risk factors. Results: Among 712 women, 56% had hypertension and 83% were aware of their diagnosis. Of those aware, 83% were using antihypertensive medication, and 63% of those treated had controlled hypertension. In adjusted analyses, non-Hispanic White and Hispanic women had 31% and 48% lower prevalence of hypertension than non-Hispanic Black women, respectively. Women living with HIV who had hypertension were 19% (P = .04) more likely to be taking antihypertension medication when compared with women living without HIV. Conclusions: In this study population of women living with and without HIV in the US South, the prevalence of hypertension was lowest among Hispanic women and highest among non-Hispanic Black women. Despite similar hypertension prevalence, women living with HIV were more likely to be taking antihypertensive medication when compared with women living without HIV.

Subclinical Atherosclerosis Across the Menopausal Transition in Women With and Without HIV.

The menopausal transition is a pivotal time of cardiovascular risk, but knowledge is limited in HIV. We studied longitudinal carotid artery intima-media thickness (CIMT) in the Women's Interagency HIV Study (2004-2019; 979 women/3247 person-visits; 72% with HIV). Among women with HIV only, those who transitioned had greater age-related CIMT progression compared to those remaining premenopausal (difference in slope = 1.64 µm/year, P = .002); and CIMT increased over time in the pretransition (3.47 µm/year, P = .002) and during the menopausal transition (9.41 µm/year, P < .0001), but not posttransition (2.9 µm/year, P = .19). In women with HIV, menopause may accelerate subclinical atherosclerosis as measured by CIMT.

Common antiretroviral combinations are associated with somatic depressive symptoms in women with HIV.

OBJECTIVE: While modern antiretroviral therapy (ART) is highly effective and safe, depressive symptoms have been associated with certain ART drugs. We examined the association between common ART regimens and depressive symptoms in women with HIV (WWH) with a focus on somatic vs. nonsomatic symptoms. DESIGN: Analysis of longitudinal data from the Women's Interagency HIV Study. METHODS: Participants were classified into three groups based on the frequency of positive depression screening (CES-D ≥16): chronic depression (≥50% of visits since study enrollment), infrequent depression (<50% of visits), and never depressed (no visits). Novel Bayesian machine learning methods building upon a subset-tree kernel approach were developed to estimate the combined effects of ART regimens on depressive symptoms in each group after covariate adjustment. RESULTS: The analysis included 1538 WWH who participated in 12 924 (mean = 8.4) visits. The mean age was 49.9 years, 72% were Black, and 14% Hispanic. In the chronic depression group, combinations including tenofovir alafenamide and cobicistat-boosted elvitegravir and/or darunavir were associated with greater somatic symptoms of depression, whereas those combinations containing tenofovir disoproxil fumarate and efavirenz or rilpivirine were associated with less somatic depressive symptoms. ART was not associated with somatic symptoms in the infrequent depression or never depressed groups. ART regimens were not associated with nonsomatic symptoms in any group. CONCLUSIONS: Specific ART combinations are associated with somatic depressive symptoms in WWH with chronic depression. Future studies should consider specific depressive symptoms domains as well as complete drug combinations when assessing the relationship between ART and depression.

Association of Higher Intake of Plant-Based Foods and Protein With Slower Kidney Function Decline in Women With HIV.

BACKGROUND: We investigated whether there exists an association between dietary acid load and kidney function decline in women living with HIV (WLWH) receiving antiretroviral therapy (ART). SETTING: One thousand six hundred eight WLWH receiving ART in the WIHS cohort with available diet data and a baseline estimated glomerular filtration rate (eGFR) ≥15 mL/minute/1.73 m2. METHODS: A brief dietary instrument conducted from 2013 to 2016 under the Food Insecurity Sub-Study was used for assessing fruits and vegetables (FV) and protein intake. A mixed-effects model with random intercept and slope was used to estimate subjects' annual decline rate in eGFR and the association between FV intake and eGFR decline, adjusting for sociodemographics, serum albumin, comorbidities, time on ART, ART drugs, HIV markers, and baseline eGFR. We evaluated whether markers of inflammation mediated the effect of FV intake on decline in eGFR, using causal mediation analysis. RESULTS: We found a dose-response relationship for the association of FV intake and eGFR decline, with lesser annual decline in eGFR in the middle and highest tertiles of FV intake. An increase of 5 servings of FV intake per day was associated with a lower annual eGFR decline (-1.18 [-1.43, -0.94]). On average, 39% of the association between higher FV intake and slower eGFR decline was explained by decreased levels of inflammation. CONCLUSIONS: Plant-rich diet was associated with slower decline in kidney function. Inflammation is a potential path through which diet may affect kidney function. The findings support an emerging body of literature on the potential benefits of plant-rich diets for prevention of chronic kidney disease.

Plasma Glycomic Markers of Accelerated Biological Aging During Chronic HIV Infection.

People with HIV (PWH) experience an increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors that contribute to or are associated with this vulnerability remain uncertain. In the general population, alterations in the glycomes of circulating IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG glycomes of cross-sectional and longitudinal samples from 1,216 women and men, both living with virally suppressed HIV and those without HIV. Our glycan-based machine learning models indicate that living with chronic HIV significantly accelerates the accumulation of pro-aging-associated glycomic alterations. Consistently, PWH exhibit heightened expression of senescence-associated glycan-degrading enzymes compared to their controls. These glycomic alterations correlate with elevated markers of inflammatory aging and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit reduced anti-HIV IgG-mediated innate immune functions. These findings hold significant potential for the development of glycomic-based biomarkers and tools to identify and prevent premature aging and comorbidities in people living with chronic viral infections.

Aging-Related Comorbidity Burden Among Women and Men With or At-Risk for HIV in the US, 2008-2019.

Importance: Despite aging-related comorbidities representing a growing threat to quality-of-life and mortality among persons with HIV (PWH), clinical guidance for comorbidity screening and prevention is lacking. Understanding comorbidity distribution and severity by sex and gender is essential to informing guidelines for promoting healthy aging in adults with HIV. Objective: To assess the association of human immunodeficiency virus on the burden of aging-related comorbidities among US adults in the modern treatment era. Design, Setting, and Participants: This cross-sectional analysis included data from US multisite observational cohort studies of women (Women's Interagency HIV Study) and men (Multicenter AIDS Cohort Study) with HIV and sociodemographically comparable HIV-seronegative individuals. Participants were prospectively followed from 2008 for men and 2009 for women (when more than 80% of participants with HIV reported antiretroviral therapy use) through last observation up until March 2019, at which point outcomes were assessed. Data were analyzed from July 2020 to April 2021. Exposures: HIV, age, sex. Main Outcomes and Measures: Comorbidity burden (the number of total comorbidities out of 10 assessed) per participant; secondary outcomes included individual comorbidity prevalence. Linear regression assessed the association of HIV status, age, and sex with comorbidity burden. Results: A total of 5929 individuals were included (median [IQR] age, 54 [46-61] years; 3238 women [55%]; 2787 Black [47%], 1153 Hispanic or other [19%], 1989 White [34%]). Overall, unadjusted mean comorbidity burden was higher among women vs men (3.4 [2.1] vs 3.2 [1.8]; P = .02). Comorbidity prevalence differed by sex for hypertension (2188 of 3238 women [68%] vs 2026 of 2691 men [75%]), psychiatric illness (1771 women [55%] vs 1565 men [58%]), dyslipidemia (1312 women [41%] vs 1728 men [64%]), liver (1093 women [34%] vs 1032 men [38%]), bone disease (1364 women [42%] vs 512 men [19%]), lung disease (1245 women [38%] vs 259 men [10%]), diabetes (763 women [24%] vs 470 men [17%]), cardiovascular (493 women [15%] vs 407 men [15%]), kidney (444 women [14%] vs 404 men [15%]) disease, and cancer (219 women [7%] vs 321 men [12%]). In an unadjusted model, the estimated mean difference in comorbidity burden among women vs men was significantly greater in every age strata among PWH: age under 40 years, 0.33 (95% CI, 0.03-0.63); ages 40 to 49 years, 0.37 (95% CI, 0.12-0.61); ages 50 to 59 years, 0.38 (95% CI, 0.20-0.56); ages 60 to 69 years, 0.66 (95% CI, 0.42-0.90); ages 70 years and older, 0.62 (95% CI, 0.07-1.17). However, the difference between sexes varied by age strata among persons without HIV: age under 40 years, 0.52 (95% CI, 0.13 to 0.92); ages 40 to 49 years, -0.07 (95% CI, -0.45 to 0.31); ages 50 to 59 years, 0.88 (95% CI, 0.62 to 1.14); ages 60 to 69 years, 1.39 (95% CI, 1.06 to 1.72); ages 70 years and older, 0.33 (95% CI, -0.53 to 1.19) (P for interaction = .001). In the covariate-adjusted model, findings were slightly attenuated but retained statistical significance. Conclusions and Relevance: In this cross-sectional study, the overall burden of aging-related comorbidities was higher in women vs men, particularly among PWH, and the distribution of comorbidity prevalence differed by sex. Comorbidity screening and prevention strategies tailored by HIV serostatus and sex or gender may be needed.

The replication-competent HIV reservoir is a genetically restricted, younger subset of the overall pool of HIV proviruses persisting during therapy, which is highly genetically stable over time.

Within-host HIV populations continually diversify during untreated infection, and members of these diverse forms persist within infected cell reservoirs, even during antiretroviral therapy (ART). Characterizing the diverse viral sequences that persist during ART is critical to HIV cure efforts, but our knowledge of on-ART proviral evolutionary dynamics remains incomplete, as does our understanding of the differences between the overall pool of persisting proviral DNA (which is largely genetically defective) and the subset of intact HIV sequences capable of reactivating. Here, we reconstructed within-host HIV evolutionary histories in blood from seven participants of the Women's Interagency HIV Study (WIHS) who experienced HIV seroconversion. We measured diversity, lineage origins and ages of proviral sequences (env-gp120) sampled up to four times, up to 12 years on ART. We used the same techniques to study HIV sequences emerging from the reservoir in two participants. Proviral clonality generally increased over time on ART, with clones frequently persisting across multiple time points. The integration dates of proviruses persisting on ART generally spanned the duration of untreated infection (though were often skewed towards years immediately pre-ART), while in contrast, reservoir-origin viremia emerging in plasma was exclusively "younger" (i.e., dated to the years immediately pre-ART). The genetic and age distributions of distinct proviral sequences remained highly stable during ART in all but one participant in whom, after 12 years, there was evidence that "younger" proviruses had been preferentially eliminated. Analysis of within-host recombinant proviral sequences also suggested that HIV reservoirs can be superinfected with virus reactivated from an older era, yielding infectious viral progeny with mosaic genomes of sequences with different ages. Overall, results underscore the remarkable genetic stability of distinct proviral sequences that persist on ART, yet suggest that replication-competent HIV reservoir represents a genetically-restricted and overall "younger" subset of the overall persisting proviral pool in blood.

Midlife body mass index, central adiposity and neuropsychological performance over 10 years in women living with and without HIV.

Background and objective: Observations of overweight and obesity in association with neuropsychological performance (NP) vary over the adult life course depending on baseline levels, biological sex, age, race, temporality of measurements, and other factors. Therefore, similar published analyses across cohorts are inconsistent. In our sample of women living with HIV (WLWH) and women without HIV (WWOH), we conducted comparable analyses as those published in men with and without HIV. We examined cross-sectional and longitudinal associations between body mass index (BMI) and waist circumference (WC) and NP. Methods: Four hundred thirty two 432 virologically-suppressed WLWH and 367 WWOH, ≥40 years in the Women's Interagency HIV Study (WIHS) with anthropometry and NP assessments every two years from 2009-2019 were included in the study. Demographically-adjusted T-scores were calculated for six NP domains: learning, memory, executive function, processing speed, attention and working memory, and motor function. Multivariable linear regression models stratified by HIV status were used to examine cross-sectional associations of BMI and WC by NP domain; repeated measures analyses assessed baseline BMI and WC in association with longitudinal change in NP. Covariates included sociodemographic, behavioral, and HIV-related characteristics. Results: At baseline among all women, the median age was 45 years, 65% were Non-Latinx Black women, and 45% were obese women. Obese WLWH (BMI≥30.0 kg/m2) had poorer executive function (ß=-2.27, 95%CI [-4.46, -0.07]) versus WLWH with healthy BMI (18.5-24.9 kg/m2). Longitudinally over ~8 years, obese versus overweight WWOH improved on memory (ß=2.19, 95%CI [0.13, 4.26]), however overweight versus healthy WWOH experienced declining memory (ß= -2.67, 95%CI [-5.40, -0.07]). Increasing WC was associated with declining executive, processing speed, and motor function (p's<0.05); an at-risk WC was associated with improved memory (ß=1.81, 95%CI [0.19, 3.44]) among WWOH. Among WLWH, increasing BMI was associated with improved learning (ß=0.07, 95%CI [0.00, 0.15]. Conclusion: Our cross-sectional and longitudinal analyses evaluating the associations of BMI and WC and NP were mixed compared to previous reports. This illustrates the importance of sociodemographic characteristics, baseline levels of exposures and outcomes, HIV status, temporality of measurements, and other factors when evaluating aging HIV epidemiology study results.

Cumulative Human Immunodeficiency Virus (HIV)-1 Viremia Is Associated With Increased Risk of Multimorbidity Among US Women With HIV, 1997-2019.

Background: To evaluate the effect of cumulative human immunodeficiency virus (HIV)-1 viremia on aging-related multimorbidity among women with HIV (WWH), we analyzed data collected prospectively among women who achieved viral suppression after antiretroviral therapy (ART) initiation (1997-2019). Methods: We included WWH with ≥2 plasma HIV-1 viral loads (VL) <200 copies/mL within a 2-year period (baseline) following self-reported ART use. Primary outcome was multimorbidity (≥2 nonacquired immune deficiency syndrome comorbidities [NACM] of 5 total assessed). The trapezoidal rule calculated viremia copy-years (VCY) as area-under-the-VL-curve. Cox proportional hazard models estimated the association of time-updated cumulative VCY with incident multimorbidity and with incidence of each NACM, adjusting for important covariates (eg, age, CD4 count, etc). Results: Eight hundred six WWH contributed 6368 women-years, with median 12 (Q1-Q3, 7-23) VL per participant. At baseline, median age was 39 years, 56% were Black, and median CD4 was 534 cells/mm3. Median time-updated cumulative VCY was 5.4 (Q1-Q3, 4.7-6.9) log10 copy-years/mL. Of 211 (26%) WWH who developed multimorbidity, 162 (77%) had incident hypertension, 133 (63%) had dyslipidemia, 60 (28%) had diabetes, 52 (25%) had cardiovascular disease, and 32 (15%) had kidney disease. Compared with WWH who had time-updated cumulative VCY <5 log10, the adjusted hazard ratio of multimorbidity was 1.99 (95% confidence interval [CI], 1.29-3.08) and 3.78 (95% CI, 2.17-6.58) for those with VCY 5-6.9 and ≥7 log10 copy-years/mL, respectively (P < .0001). Higher time-updated cumulative VCY increased the risk of each NACM. Conclusions: Among ART-treated WWH, greater cumulative viremia increased the risk of multimorbidity and of developing each NACM, and hence this may be a prognostically useful biomarker for NACM risk assessment in this population.

Intersectionality of Socioecological Factors Associated With Cognitive Function Among Older Women With HIV in the United States: A Structural Equation Model Analysis Using Data From the Women's Interagency HIV Study.

ABSTRACT: Increased life expectancy of people with HIV has health implications including the intersection of the long-term use of antiretroviral treatment, inflammatory events, and age-related immunosenescence. In a cross-sectional study utilizing using the Socio-Eecological Model, we identified pathways of cognitive function (CF) among 448 women with HIV, 50 years and older. A structural equation model showed the direct effects of mood (ß = -0.25, p < .01), comorbidities (ß = --0.13, p < .05), race (ß = --0.13, p < .05), and abuse (ß = 0.27, p < .001) on the latent variable CF. Substance and alcohol use, depressive symptoms, cigarette smoking, and the number of comorbidities are important considerations when designing interventions utilizing using a multi-level and intersectional lens to maximize positive CF outcomes.

The Effect of Menopausal Status, Age, and Human Immunodeficiency Virus (HIV) on Non-AIDS Comorbidity Burden Among US Women.

Menopause may impact the earlier onset of aging-related comorbidities among women with versus without human immunodeficiency virus (HIV). We found that menopausal status, age, and HIV were independently associated with higher comorbidity burden, and that HIV impacted burden most in the pre-/perimenopausal phases.

Integrase Inhibitors are Associated with Neuropsychiatric Symptoms in Women with HIV.

OBJECTIVE: Women with HIV(WWH) are more likely to discontinue/change antiretroviral therapy(ART) due to side effects including neuropsychiatric symptoms. Efavirenz and integrase strand transfer inhibitors(INSTIs) are particularly concerning. We focused on these ART agents and neuropsychiatric symptoms in previously developed subgroups of WWH that differed on key sociodemographic factors as well as longitudinal behavioral and clinical profiles. WWH from the Women's Interagency HIV Study were included if they had ART data available, completed the Perceived Stress Scale-10 and PTSD Checklist-Civilian. Questionnaires were completed biannually beginning in 2008 through 2016. To examine ART-symptom associations, constrained continuation ratio model via penalized maximum likelihood were fit within 5 subgroups of WWH. Data from 1882 WWH contributed a total of 4598 observations. 353 women were previously defined as primarily having well-controlled HIV with vascular comorbidities, 463 with legacy effects(CD4 nadir < 250cells/mL), 274 aged ≤ 45 with hepatitis, 453 between 35-55 years, and 339 with poorly-controlled HIV/substance users. INSTIs, but not efavirenz, were associated with symptoms among key subgroups of WWH. Among those with HIV legacy effects, dolutegravir and elvitegravir were associated with greater stress/anxiety and avoidance symptoms(P's < 0.01); dolutegravir was also associated with greater re-experiencing symptoms(P = 0.005). Elvitegravir related to greater re-experiencing and hyperarousal among women with well-controlled HIV with vascular comorbidities(P's < 0.022). Raltegravir was associated with less hyperarousal, but only among women aged ≤ 45 years(P = 0.001). The adverse neuropsychiatric effects of INSTIs do not appear to be consistent across all WWH. Key characteristics (e.g., age, hepatitis positivity) may need consideration to fully weight the risk-benefit ratio of dolutegravir and elvitegravir in WWH.

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

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Rapid Point-of-Care Test Kit for Bacterial Vaginosis: Detection of Vaginolysin and Clue Cells Using Paper Strips and a Smartphone.

There is an unmet need for a point-of-care test that is accurate, affordable, and simple to diagnose bacterial vaginosis, the most common cause of vaginal symptoms among women. Bacterial vaginosis leaves patients with undesirable vaginal discharge, malodor, and discomfort. Currently, the diagnosis of bacterial vaginosis is inaccurate and complex, leading to high rates of misdiagnosis. Inaccurate diagnoses are unsafe as bacterial vaginosis increases the risks of acquiring sexually transmitted infections as well as the likelihood of miscarriages. To date, the most commonly identified bacteria associated with bacterial vaginosis is Gardnerella vaginalis. We developed a method for the expression, purification, and detection of vaginolysin, the most well-characterized virulence factor of G. vaginalis. Elevated levels of G. vaginalis have been shown to lead to a toxic vaginal environment, facilitating bacterial vaginosis. We have developed an enzyme-linked immunosorbent assay for the detection of vaginolysin, which was translated to a lateral flow assay for use in a rapid, straightforward, cost-effective paper-based diagnostic test for vaginolysin that does not require the use of instrumentation. In conjunction, we have employed a commercially available smartphone microscopy kit to visualize clue cells without the need for equipment or electricity. The combination of these methodologies allows for an accurate and easy approach to diagnose bacterial vaginosis with minimal resources for use in any setting.

Mechanisms linking gender-based violence to worse HIV treatment and care outcomes among women in the United States.

OBJECTIVE: To 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). DESIGN: We analyzed longitudinal data collected among 1717 WLHIV in the Women's Interagency HIV Study (WIHS). METHODS: From 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 (<95%) adherence and at least one missed HIV care appointment without rescheduling in the past 6 months. Mediation analyses were performed to test whether heavy drinking and illicit drug use mediated the associations between GBV and the two HIV outcomes. RESULTS: The mean age was 47 (standard deviation = 9), 5% reported experiencing GBV, 17% reported suboptimal adherence and 15% reported at least one missed appointment in the past 6 months. Women who experienced GBV had a significantly higher odds of suboptimal adherence [adjusted odds ratio (aOR) = 1.99; 95% confidence interval (CI) = 1.40-2.83] and missed appointments (aOR = 1.92, 95% CI = 1.32-2.33). Heavy drinking and illicit drug use mediated 36 and 73% of the association between GBV and suboptimal adherence and 29 and 65% of the association between GBV and missed appointments, respectively. CONCLUSIONS: Substance use is an underlying mechanism through which GBV affects outcomes along the HIV care continuum among WLHIV in the US. To optimize HIV treatment and care among women, interventions should address the combined epidemics of substance use, violence, and HIV.