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ObjectiveOur purpose was to assess whether participation in needle exchange programs (NEPs) influenced incident hepatitis C virus (HCV) infection through effects on injection risk behaviors among young injection drug users (IDUs) in the United States.MethodsData were drawn from three multi-site studies carried out in four major cities that enrolled IDUs over the period 1994–2004. Bivariate and multivariate analyses were conducted to assess relationships among sociodemographic characteristics, NEP use, injection risk behaviors, and prevalent or incident HCV infection.ResultsOf the total participants (n = 4663), HCV seroprevalence was 37%; among those who initially tested negative and completed follow-up at three, six, or 12 months (n = 1288), 12% seroconverted. Nearly half of participants reported NEP (46%) use at baseline. Multivariate results showed no significant relationship between NEP use and HCV seroconversion. Controlling for sociodemographic characteristics, IDUs reporting NEP use were significantly less likely to share needles (aOR = 0.77, 95% CI = 0.67–0.88). Additionally, controlling for sociodemographic characteristics and program use, sharing needles, sharing other injection paraphernalia, longer injection duration, and injecting daily were all positively related to prevalent infection.ConclusionsOur results suggest an indirect protective effect of NEP use on HCV infection by reducing risk behavior.

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

BackgroundAlterations in gut microbiota and blood metabolomic profiles have been implicated in HIV infection and cardiovascular disease. However, it remains unclear whether alterations in gut microbiota may contribute to disrupted host blood metabolomic profiles in relation to atherosclerosis, especially in the context of HIV infection.MethodsWe analyzed cross-sectional associations between gut microbiota features and carotid artery plaque in 361 women with or at high risk of HIV (67% HIV+), and further integrated plaque-associated microbial features with plasma lipidomic/metabolomic profiles. Furthermore, in 737 women and men, we examined prospective associations of baseline gut bacteria-associated lipidomic and metabolomic profiles with incident carotid artery plaque over 7-year follow-up.ResultsWe found 2 potentially pathogenic bacteria, Fusobacterium and Proteus, were associated with carotid artery plaque; while the beneficial butyrate producer Odoribacter was inversely associated with plaque. Fusobacterium and Proteus were associated with multiple lipids/metabolites which were clustered into 8 modules in network. A module comprised of 9 lysophosphatidylcholines and lysophosphatidylethanolamines and a module comprised of 9 diglycerides were associated with increased risk of carotid artery plaque (risk ratio [95% CI], 1.34 [1.09-1.64] and 1.24 [1.02-1.51] per SD increment, respectively). Functional analyses identified bacterial enzymes in lipid metabolism associated with these plasma lipids. In particular, phospholipase A1 and A2 are the key enzymes in the reactions producing lysophosphatidylcholines and lysophosphatidylethanolamines.ConclusionsAmong individuals with or at high risk of HIV infection, we identified altered gut microbiota and related functional capacities in the lipid metabolism associated with disrupted plasma lipidomic profiles and carotid artery atherosclerosis.

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.

PurposeThe Liver Disease and Reproductive Ageing (LIVRA) study leverages the infrastructure of the decades-long multicentre prospective Women's Interagency HIV Study (WIHS) to examine the contributions of HIV, hepatitis C virus (HCV) and ageing to liver disease progression in women.ParticipantsFrom 2013 to 2018, LIVRA enrolled 1576 participants (77 HCV-seropositive only, 248 HIV/HCV-seropositive, 868 HIV-seropositive only and 383 HIV/HCV-seronegative) who underwent vibration controlled transient elastography (VCTE). A VCTE quality assurance programme was established to ensure consistency and accuracy for longitudinal assessment of steatosis (fatty liver) via the controlled attenuation parameter (CAP) and fibrosis via liver stiffness (LS). Demographic, lifestyle factors, anthropometry, clinical and medication history, host genetics, immune markers and hormone levels were collected as part of the WIHS.Findings to dateAt baseline, 737 of 1543 women with CAP measurements had steatosis (CAP ≥248 dB/m) and 375 of 1576 women with LS measurements had significant fibrosis (LS ≥7.1 kPa), yielding a prevalence of 48% and 24%, respectively. On multivariable analysis, waist circumference (WC) and insulin resistance were independently associated with higher CAP (17.8 dB/m per 10 cm (95% CI:16.2 to 19.5) and 1.2 dB/m per doubling (95% CI:0.8 to 1.6), respectively). By contrast, HIV/HCV seropositivity and HCV seropositivity alone were associated with less steatosis compared with HIV/HCV-seronegative women, although the latter did not reach statistical significance (-9.2 dB/m (95% CI:-18.2 to -0.3) and -10.4 dB/m (95% CI: -23.8 to 3.1), respectively). Factors independently associated with higher LS were age (4.4% per 10 years (95% CI: 0.4% to 8.4%)), WC (5.0% per 10 cm (95% CI: 3.3% to 6.6%)), CAP steatosis (0.6% per 10 dB/m (95% CI: 0.1% to 1.0%)), HIV/HCV seropositivity (33% (95% CI: 24% to 44%)) and HCV seropositivity alone (43% (95% CI: 28% to 60%)). Excluding scans that were invalid based on traditional criteria for unreliability did not affect the results.Future plansEnrolled women undergo VCTE at 3-year intervals unless LS is ≥9.5 kPa, indicating advanced fibrosis, in which case VCTE is performed annually. Participants also undergo VCTE every 6 months until 18 months after HCV treatment initiation. Analysis of the data collected will provide insights into the impact of ageing/ovarian function, host genetics, immune function and contemporary HIV and HCV treatments on liver disease progression.

Objectives: To evaluate whether a behavioral intervention, which taught peer education skills, could reduce injection and sexual risk behaviors associated with primary HIV and hepatitis C virus infection (HCV) among young injection drug users (IDU).Design: We conducted a randomized controlled trial involving HIV and HCV antibodynegative IDU, aged 15–30 years, recruited in five United States cities. A six-session, small-group, cognitive behavioral, skills-building intervention in which participants were taught peer education skills (n ¼ 431) was compared with a time-equivalent attention control (n ¼ 423). Baseline visits included interviews for sociodemographic, psychosocial, and behavioral factors during the previous 3 months; HIV and HCV antibody testing; and pre/posttest counselling. Procedures were repeated 3 and 6 months postintervention.Results: The intervention produced a 29% greater decline in overall injection risk 6 months postintervention relative to the control [proportional odds ratio 0.71; 95% confidence limit (CL) 0.52, 0.97], and a 76% decrease compared with baseline. Decreases were also observed for sexual risk behaviors, but they did not differ by trial arm. Overall HCV infection incidence (18.4/100 person-years) did not differ significantlyacross trial arms (relative risk 1.15; 95% CL 0.72, 1.82). No HIV seroconversions were observed.Conclusion: Interventions providing information, enhancing risk-reduction skills, and motivating behavior change through peer education training can reduce injection risk behaviors, although risk elimination might be necessary to prevent HCV transmission.

ObjectiveOur purpose was to assess whether participation in needle exchange programs (NEPs) influenced incident hepatitis C virus (HCV) infection through effects on injection risk behaviors among young injection drug users (IDUs) in the United States.MethodsData were drawn from three multi-site studies carried out in four major cities that enrolled IDUs over the period 1994–2004. Bivariate and multivariate analyses were conducted to assess relationships among sociodemographic characteristics, NEP use, injection risk behaviors, and prevalent or incident HCV infection.ResultsOf the total participants (n = 4663), HCV seroprevalence was 37%; among those who initially tested negative and completed follow-up at three, six, or 12 months (n = 1288), 12% seroconverted. Nearly half of participants reported NEP (46%) use at baseline. Multivariate results showed no significant relationship between NEP use and HCV seroconversion. Controlling for sociodemographic characteristics, IDUs reporting NEP use were significantly less likely to share needles (aOR = 0.77, 95% CI = 0.67–0.88). Additionally, controlling for sociodemographic characteristics and program use, sharing needles, sharing other injection paraphernalia, longer injection duration, and injecting daily were all positively related to prevalent infection.ConclusionsOur results suggest an indirect protective effect of NEP use on HCV infection by reducing risk behavior.

BackgroundNeurocognitive impairment (NCI) persists among women living with HIV. Food insecurity is also common among women and may be an important modifiable contributor of NCI.ObjectiveThe goal of this study was to determine the association of food insecurity with neurocognitive function among women living with or without HIV.MethodsFrom 2013 to 2015, we analyzed data from a cross-sectional sample from the Women's Interagency HIV Study (WIHS). Measures included food insecurity and a comprehensive neuropsychological test battery assessing executive function, processing speed, attention/working memory, learning, memory, fluency, and motor function. We conducted multivariable linear regressions to examine associations between food insecurity and domain-specific neurocognitive performance, adjusting for relevant sociodemographic, behavioral, and clinical factors.ResultsParticipants (n = 1,324) were predominantly HIV seropositive (68%), Black/African-American (68%) or Hispanic (16%), and low income (48% reported

BackgroundIntegrase strand transfer inhibitors (INSTIs) have been associated with weight gain among women living with HIV. We aimed to investigate the association between INSTIs and change in cardiometabolic risk indicators.SettingRetrospective cohort.MethodsData from 2006 to 2017 were analyzed from women living with HIV enrolled in the longitudinal Women's Interagency HIV Study who were virally controlled on antiretroviral therapy (ART) for ≥5 consecutive semiannual visits. Women who switched/added an INSTI to ART (INSTI group) were compared with women who remained on non-INSTI ART (non-INSTI group). Outcomes included changes in fasting lipids and glucose, hemoglobin A1c (HbA1c), blood pressure (BP), and incident diabetes, hypertension, and insulin resistance. Outcomes were measured 6-12 months before and 6-18 months after INSTI switch/add in the INSTI group with comparable visits in the non-INSTI group. Longitudinal linear regression models compared change over time in each outcome by the study group.ResultsOne thousand one hundred eighteen participants (234 INSTI, 884 non-INSTI) were followed for a median 2.0 (Q1 1.9, Q3 2.0) years. Participants were median age 49 years, 61% Black, and 73% overweight or obese (body mass index ≥25 kg/m). Compared with non-INSTI, the INSTI group experienced greater increases in HbA1c (+0.05 vs. -0.06 mg/dL, P = 0.0318), systolic BP (+3.84 vs. +0.84 mm Hg, P = 0.0191), and diastolic BP (+1.62 vs. -0.14 mm Hg, P = 0.0121), with greatest change in HbA1c among women on INSTIs with ≥5% weight gain.ConclusionsINSTI use was associated with unfavorable changes in HbA1c and systolic and diastolic BP during short-term follow-up. Further research is needed to understand long-term cardiometabolic effects of INSTI use.

BackgroundIntegrase 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.MethodsWomen 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.ResultsWe 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.ConclusionsIn 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.

BackgroundIt is unclear whether human immunodeficiency virus (HIV) infection results in permanent loss of T-cell memory or if it affects preexisting antibodies to childhood vaccinations or infections.MethodsWe conducted a matched cohort study involving 50 pairs of HIV-infected and HIV-uninfected women. Total memory T-cell responses were measured after anti-CD3 or vaccinia virus (VV) stimulation to measure T cells elicited after childhood smallpox vaccination. VV-specific antibodies were measured by means of enzyme-linked immunosorbent assay (ELISA).ResultsThere was no difference between HIV-infected and HIV-uninfected study participants in terms of CD4+ T-cell responses after anti-CD3 stimulation (P = .19) although HIV-infected participants had significantly higher CD8+ T-cell responses (P = .03). In contrast, there was a significant loss in VV-specific CD4+ T-cell memory among HIV-infected participants (P = .04) whereas antiviral CD8+ T-cell memory remained intact (P > .99). VV-specific antibodies were maintained indefinitely among HIV-uninfected participants (half-life, infinity; 95% confidence interval, 309 years to infinity) but declined rapidly among HIV-infected participants (half-life; 39 years; 24-108 years; P = .001).ConclusionsDespite antiretroviral therapy-associated improvement in CD4+ T-cell counts (nadir, 350/μL after antiretroviral therapy), antigen-specific CD4+ T-cell memory to vaccinations or infections that occurred before HIV infection did not recover after immune reconstitution, and a previously unrealized decline in preexisting antibody responses was observed.

ObjectiveTo describe longitudinal changes in the prevalence of abnormal Papanicolau testing among women living with HIV.DesignProspective cohort study with sequential enrollment subcohorts.MethodsFour waves of enrollment occurred in the Women's Interagency HIV Study, the US women's HIV cohort (1994-1995, 2001-2002, 2011-2012, 2013-2015). Pap testing was done at intake, with colposcopy prescribed for any abnormality. Rates of abnormal Pap test results (atypical squamous cells of uncertain significance or worse) and cervical intraepithelial neoplasia grade 2 (CIN2) or worse were calculated. Logistic regression models assessed changes in prevalence across cohorts after controlling for severity of HIV disease and other risk factors for abnormal Pap tests.ResultsThe unadjusted prevalence of any Pap abnormality was 679/1769 (38%) in the original cohort, 195/684 (29%) in the 2001-2002 cohort, 46/231 (20%) in the 2011-2012 cohort, and 71/449 (16%) in the 2013-2015 cohort. In multivariable analysis, compared with risk in the 1994-1995 cohort, the adjusted risk in the 2001-2002 cohort was 0.79 (95% CI 0.59-1.05), in the 2011-2012 cohort was 0.67 (95% CI 0.43-1.04), and in the 2013-2015 cohort was 0.41 (95% CI 0.27-0.62) with P for trend less than 0.0001.ConclusionRates of abnormal cytology among women with HIV have fallen during the past two decades.

Objectives: To evaluate whether a behavioral intervention, which taught peer education skills, could reduce injection and sexual risk behaviors associated with primary HIV and hepatitis C virus infection (HCV) among young injection drug users (IDU).Design: We conducted a randomized controlled trial involving HIV and HCV antibodynegative IDU, aged 15–30 years, recruited in five United States cities. A six-session, small-group, cognitive behavioral, skills-building intervention in which participants were taught peer education skills (n ¼ 431) was compared with a time-equivalent attention control (n ¼ 423). Baseline visits included interviews for sociodemographic, psychosocial, and behavioral factors during the previous 3 months; HIV and HCV antibody testing; and pre/posttest counselling. Procedures were repeated 3 and 6 months postintervention.Results: The intervention produced a 29% greater decline in overall injection risk 6 months postintervention relative to the control [proportional odds ratio 0.71; 95% confidence limit (CL) 0.52, 0.97], and a 76% decrease compared with baseline. Decreases were also observed for sexual risk behaviors, but they did not differ by trial arm. Overall HCV infection incidence (18.4/100 person-years) did not differ significantlyacross trial arms (relative risk 1.15; 95% CL 0.72, 1.82). No HIV seroconversions were observed.Conclusion: Interventions providing information, enhancing risk-reduction skills, and motivating behavior change through peer education training can reduce injection risk behaviors, although risk elimination might be necessary to prevent HCV transmission.

We used the World Health Organization's Composite International Diagnostic Interview to determine the prevalence, comorbidity, and correlates of lifetime and 12-month behavioral health disorders in a multisite cohort of 1027 women living with HIV in the United States. Most (82.6%) had one or more lifetime disorders including 34.2% with mood disorders, 61.6% with anxiety disorders, and 58.3% with substance use disorders. Over half (53.9%) had at least one 12-month disorder, including 22.1% with mood disorders, 45.4% with anxiety disorders, and 11.1% with substance use disorders. Behavioral health disorder onset preceded HIV diagnosis by an average of 19 years. In multivariable models, likelihood of disorders was associated with women's race/ethnicity, employment status, and income. Women with 12-month behavioral health disorders were significantly more likely than their counterparts to engage in subsequent sexual and substance use HIV risk behaviors. We discuss the complex physical and behavioral health needs of women living with HIV.

Unstable housing, including homelessness, is a public policy concern for all populations, and more critically for people with a serious health condition such as HIV. We measure the effect of unstable housing on HIV treatment biomarkers: viral suppression (viral load 350 cells per μl). We use panel data (1995-2015) from 3082 participants of the Women's Interagency HIV Study (WIHS) sites in Bronx and Brooklyn (NY), Chicago (IL), Los Angeles and San Francisco (CA), and Washington (DC). The instrumental variable (IV) measures allocations for the Housing Opportunities for People with AIDS (HOPWA) per person newly infected with HIV, and it represents actual availability of housing assistance for HIV-positive persons at the metropolitan area level. Using an extended probit model with the IV, we find that unstable housing reduces the likelihood of viral suppression by 51 percentage points, and decreases the probability of having adequate CD4 cell count by 53 percentage points. The endogeneity-corrected results are larger than naïve probits, which show decreases of 8.1 and 7.8 percentage points, respectively. The hypothesized pathways for the effect are: decreased use of mental healthcare/counseling, any healthcare, and less continuity of care. Increasing efforts to improve housing assistance, including HOPWA, and other interventions to make housing more affordable for low-income populations, and HIV-positive populations in particular, may be warranted not only for the benefits of stable housing, but also to improve HIV-related biomarkers.

ObjectivesA fracture risk assessment tool (FRAX) using clinical risk factors (CRFs) alone underestimates fracture risk in HIV-infected men. Our objective was to determine whether accuracy of FRAX would be improved by considering HIV as a cause of secondary osteoporosis, and further improved with addition of dual-energy X-ray absorptiometry parameters in HIV-infected women.DesignSubgroup analysis of Women's Interagency HIV Study.MethodsWe included 1148 women (900 HIV-infected and 248 uninfected) over age 40 with data to approximate FRAX CRFs and 10-year observational data for incident fragility fractures; 181 (20%) HIV-infected women had dual-energy X-ray absorptiometry data. Accuracy of FRAX was evaluated by the observed/estimated ratios of fracture in four models: CRFs alone; CRFs with HIV included as a cause of secondary osteoporosis; CRFs and femoral neck bone mineral density (FN BMD); and CRFs, FN BMD and trabecular bone score.ResultsFRAX using CRFs were less accurate in HIV-infected than uninfected women for major osteoporotic (observed/estimated ratio: 5.05 vs. 3.26, P

IntroductionThis study assessed longitudinal relationships between patient healthcare empowerment, engagement in care, and viral control in the Women's Interagency HIV Study, a prospective cohort study of U.S. women living with HIV.MethodsFrom April 2014 to March 2016, four consecutive 6-month visits were analyzed among 973 women to assess the impact of Time 1 healthcare empowerment variables (Tolerance for Uncertainty and the state of Informed Collaboration Committed Engagement) on Time 2 reports of ≥95% HIV medication adherence and not missing an HIV primary care appointment since last visit; and on HIV RNA viral control across Times 3 and 4, controlling for illicit drug use, heavy drinking, depression symptoms, age, and income. Data were analyzed in 2017.ResultsAdherence of ≥95% was reported by 83% of women, 90% reported not missing an appointment since the last study visit, and 80% were categorized as having viral control. Logistic regression analyses revealed a significant association between the Informed Collaboration Committed Engagement subscale and viral control, controlling for model covariates (AOR=1.08, p=0.04), but not for the Tolerance for Uncertainty subscale and viral control (AOR=0.99, p=0.68). In separate mediation analyses, the indirect effect of Informed Collaboration Committed Engagement on viral control through adherence (β=0.04, SE=0.02, 95% CI=0.02, 0.08), and the indirect effect of Informed Collaboration Committed Engagement on viral control through retention (β=0.01, SE=0.008, 95% CI=0.001, 0.030) were significant. Mediation analyses with Tolerance for Uncertainty as the predictor did not yield significant indirect effects.ConclusionsThe Informed Collaboration Committed Engagement healthcare empowerment component is a promising pathway through which to promote engagement in care among women living with HIV.

ObjectiveHIV is a cardiovascular disease (CVD) risk factor. However, CVD risk is often underestimated in HIV-infected women. C-reactive protein (CRP) may improve CVD prediction in this population. We examined the association of baseline plasma CRP with subclinical CVD in women with and without HIV.DesignRetrospective cohort study.MethodsA total of 572 HIV-infected and 211 HIV-uninfected women enrolled in the Women's Interagency HIV Study underwent serial high-resolution B-mode carotid artery ultrasonography between 2004 and 2013 to assess carotid intima-media thickness (CIMT) and focal carotid artery plaques. We used multivariable linear and logistic regression models to assess the association of baseline high (≥3 mg/l) high-sensitivity (hs) CRP with baseline CIMT and focal plaques, and used multivariable linear and Poisson regression models for the associations of high hsCRP with CIMT change and focal plaque progression. We stratified our analyses by HIV status.ResultsMedian (interquartile range) hsCRP was 2.2 mg/l (0.8-5.3) in HIV-infected, and 3.2 mg/l (0.9-7.7) in HIV-uninfected, women (P = 0.005). There was no statistically significant association of hsCRP with baseline CIMT [adjusted mean difference -3.5 μm (95% confidence interval:-19.0 to 12.1)] or focal plaques [adjusted odds ratio: 1.31 (0.67-2.67)], and no statistically significant association of hsCRP with CIMT change [adjusted mean difference 11.4 μm (-2.3 to 25.1)]. However, hsCRP at least 3 mg/l was positively associated with focal plaque progression in HIV-uninfected [adjusted rate ratio: 5.97 (1.46-24.43)], but not in HIV-infected [adjusted rate ratio: 0.81 (0.47-1.42)] women (P = 0.042 for interaction).ConclusionIn our cohort of women with similar CVD risk factors, higher baseline hsCRP is positively associated with carotid plaque progression in HIV-uninfected, but not HIV-infected, women, suggesting that subclinical CVD pathogenesis may be different HIV-infected women.

BackgroundAlthough fracture rates are higher in HIV+ than HIV- women, whether HIV infection increases risk of falls is unclear. We determined the longitudinal occurrence and risk factors for falls in the Women's Interagency HIV Study (WIHS), and explored associations with cognitive complaints.MethodsRecent (prior 6 months) self-reported falls were collected in 1,816 (1,250 HIV+; 566 HIV-) women over 24 months. Generalized estimating equation models using stepwise selection determined odds of any fall (versus none).ResultsHIV+ women were older than HIV- women (median 49 versus 47 years; P=0.0004), more likely to report neuropathy (20% versus 16%; P=0.023), and had greater central nervous system (CNS) medication use. At least one fall was reported in 41% HIV+ versus 42% HIV- women, including ≥2 falls in 25% HIV+ and 24% HIV- (overall P=0.30). Cognitive complaints were associated with falls among HIV+ (odds ratio [OR] 2.38; 95% CI 1.83, 3.09) and HIV- women (OR 3.43; 95% CI 2.37, 4.97); in adjusted models, cognitive complaints remained significant only in HIV- women (adjusted [aOR] 2.26; 95% CI 1.46, 3.48). Factors associated with any fall in adjusted analyses included: depressive symptoms and neuropathy (both HIV+ and HIV-); age, marijuana use, multiple CNS medications, and HCV infection (HIV+ only); and cognitive complaints, quality of life, hypertension and obesity (HIV- only).ConclusionsMiddle-aged HIV+ and HIV- women had similar fall rates. Among HIV+ women, factors affecting cognition such as age, depressive symptoms, marijuana use and multiple CNS medications were important predictors of falls, however, cognitive complaints were not.

BackgroundHeavy alcohol use can lead to progressive liver damage, especially in individuals with chronic hepatitis C (HCV); however, the impact of nonheavy use is not clear. We studied long-term effects of modest alcohol use on fibrosis progression in a large cohort of women coinfected with human immunodeficiency virus (HIV)/HCV.MethodsAlcohol intake was ascertained every 6 months and use categorized as abstinent, light (1-3 drinks/week), moderate (4-7 drinks/week), heavy (>7 drinks/week), and very heavy (>14 drinks/week). Fibrosis progression was defined as the change in Fibrosis-4 Index for Liver Fibrosis (FIB-4) units per year using random-intercept, random-slope mixed modeling.ResultsAmong 686 HIV/HCV-coinfected women, 46.0% reported no alcohol use; 26.8% reported light use, 7.1% moderate use, and 19.7% heavy use (6.7% had 8-14 drinks/week and 13.0% had >14 drinks/week) at cohort entry. Median FIB-4 at entry was similar between groups. On multivariable analysis, compared to abstainers, light and moderate alcohol use was not associated with fibrosis progression (0.004 [95% confidence interval {CI}, -.11 to .12] and 0.006 [95% CI, -.18 to .19] FIB-4 units/year, respectively). Very heavy drinking (>14 drinks/week) showed significant fibrosis acceleration (0.25 [95% CI, .01-.49] FIB-4 units/year) compared to abstaining, whereas drinking 8-14 drinks per week showed minimal acceleration of fibrosis progression (0.04 [95% CI, -.19 to .28] FIB-4 units/year).ConclusionsLight/moderate alcohol use was not substantially associated with accelerated fibrosis progression, whereas drinking >14 drinks per week showed increased rates of fibrosis progression. Women with HIV/HCV infection should be counseled against heavy alcohol consumption, but complete abstinence may not be required to prevent accelerated liver fibrosis progression.

There is limited research examining the sexual health and well-being of older women living with HIV (OWLH). Most studies focus on sexual dysfunction, leaving aside the richer context of sexuality and sexual health, including the effect of age-related psychosocial and interpersonal changes on sexual health behaviors. Guided by the integrative biopsychosocial model and the sexual health model, this study explored the importance of sex and sexuality among OWLH to identify their sexual health and HIV prevention needs for program planning. A purposive sample (n = 50) of OWLH was selected from a parent study (n = 2052). We conducted 8 focus groups and 41 in-depth interviews with 50 African American and Latina OWLH aged 50-69 years old in three U.S. cities. The triangulation approach was used to synthesize the data. Six salient themes emerged: sexual pleasure changes due to age, sexual freedom as women age, the role of relationships in sexual pleasure, changes in sexual ability and sexual health needs, sexual risk behaviors, and ageist assumptions about older women's sexuality. We found that sexual pleasure and the need for intimacy continue to be important for OWLH, but that changing sexual abilities and sexual health needs, such as the reduction of sexual desire, as well as increased painful intercourse due to menopause-associated vaginal drying, were persistent barriers to sexual fulfillment and satisfaction. Particular interpersonal dynamics, including low perceptions of the risk of HIV transmission as related to gender, viral suppression, and habitual condomless sex with long-term partners without HIV transmission have resulted in abandoning safer sex practices with serodiscordant partners. These findings suggest that HIV prevention for OWLH should focus on how sexual function and satisfaction intersect with sexual risk. HIV prevention for OWLH should promote ways to maintain satisfying and safe sex lives among aging women.

A subset of HIV-infected individuals termed elite controllers (ECs) maintain CD4+ T cell counts and control viral replication in the absence of antiretroviral therapy (ART). Systemic cytokine responses may differentiate ECs from subjects with uncontrolled viral replication or from those who require ART to suppress viral replication. We measured 87 cytokines in four groups of women: 73 ECs, 42 with pharmacologically suppressed viremia (ART), 42 with uncontrolled viral replication (noncontrollers [NCs]), and 48 HIV-uninfected (NEG) subjects. Four cytokines were elevated in ECs but not NCs or ART subjects: CCL14, CCL21, CCL27, and XCL1. In addition, median stromal cell-derived factor-1 (SDF-1) levels were 43% higher in ECs than in NCs. The combination of the five cytokines suppressed R5 and X4 virus replication in resting CD4+ T cells, and individually SDF-1β, CCL14, and CCL27 suppressed R5 virus replication, while SDF-1β, CCL21, and CCL14 suppressed X4 virus replication. Functional studies revealed that the combination of the five cytokines upregulated CD69 and CCR5 and downregulated CXCR4 and CCR7 on CD4+ T cells. The CD69 and CXCR4 effects were driven by SDF-1, while CCL21 downregulated CCR7. The combination of the EC-associated cytokines induced expression of the anti-HIV host restriction factors IFITM1 and IFITM2 and suppressed expression of RNase L and SAMHD1. These results identify a set of cytokines that are elevated in ECs and define their effects on cellular activation, HIV coreceptor expression, and innate restriction factor expression. This cytokine pattern may be a signature characteristic of HIV-1 elite control, potentially important for HIV therapeutic and curative strategies.IMPORTANCE Approximately 1% of people infected with HIV control virus replication without taking antiviral medications. These subjects, termed elite controllers (ECs), are known to have stronger immune responses targeting HIV than the typical HIV-infected subject, but the exact mechanisms of how their immune responses control infection are not known. In this study, we identified five soluble immune signaling molecules (cytokines) in the blood that were higher in ECs than in subjects with typical chronic HIV infection. We demonstrated that these cytokines can activate CD4+ T cells, the target cells for HIV infection. Furthermore, these five EC-associated cytokines could change expression levels of intrinsic resistance factors, or molecules inside the target cell that fight HIV infection. This study is significant in that it identified cytokines elevated in subjects with a good immune response against HIV and defined potential mechanisms as to how these cytokines could induce resistance to the virus in target cells.

ObjectivePeople living with HIV (PLWH) have chronic immune activation and increased cardiovascular disease (CVD) risk. Activation of monocytes and T lymphocytes causes upregulation of glucose transporter-1 (GLUT1) for efficient function. PLWH have an increased percentage of GLUT1-expressing monocytes and T lymphocytes, but it is unclear if these cells are associated with CVD. We evaluated the expression of GLUT1 and CD38 on monocyte and T lymphocyte populations from HIV-infected women with subclinical CVD.MethodsParticipants with more than 75th percentile (n = 15) and less than 25th percentile (n = 15) age-adjusted intima-media thickness (IMT) at the right common carotid artery and bifurcation were identified from the Women's Interagency HIV Study. Groups were matched by age, race/ethnicity, smoking status, and CD4 cell count. All women were receiving suppressive antiretroviral therapy except for one high and one low IMT participant. Monocyte and T lymphocyte populations were evaluated for GLUT1 and CD38 expression using flow cytometry.ResultsIntermediate monocytes from high IMT women had significantly increased expression of GLUT1 (310 MFI vs. 210 MFI, P = 0.024) (66.4% vs. 48.5%, P = 0.031) and CD38 (339 MFI vs. 211 MFI, P = 0.002) (10.5% vs. 3.8%, P = 0.0002) compared with women with low IMT. High and low IMT participants showed no differences in GLUT1 or CD38 expression on classical monocytes, nonclassical monocytes, CD4 and CD8 T lymphocytes.ConclusionGLUT1-expressing intermediate monocytes are elevated in HIV-infected women with subclinical CVD. These cells may contribute to development of CVD in PLWH and could be a novel target to limit inflammation.

Background Cognitive impairment persists despite suppression of plasma human immunodeficiency virus (HIV) RNA. Monocyte-related immune activation is a likely mechanism. We examined immune activation and cognition in a cohort of HIV-infected and uninfected women from the Women's Interagency HIV Study (WIHS).Methods Blood levels of activation markers, soluble CD163 (sCD163), soluble CD14 (sCD14), CRP, IL-6, and a gut microbial translocation marker (intestinal fatty acid binding protein (I-FABP)) were measured in 253 women (73% HIV-infected). Markers were compared to concurrent (within ± one semiannual visit) neuropsychological testing performance.Results Higher sCD163 levels were associated with worse overall performance and worse verbal learning, verbal memory, executive function, psychomotor speed, and fine motor skills (P < .05 for all comparisons). Higher sCD14 levels were associated with worse verbal learning, verbal memory, executive function, and psychomotor speed (P < .05 for all comparisons). Among women with virological suppression, sCD163 remained associated with overall performance, verbal memory, psychomotor speed, and fine motor skills, and sCD164 remained associated with executive function (P < .05 for all comparisons). CRP, IL-6, and I-FABP were not associated with worse cognitive performance.Conclusions Monocyte activation was associated with worse cognitive performance, and associations persisted despite viral suppression. Persistent inflammatory mechanisms related to monocytes correlate to clinically pertinent brain outcomes.

Cardiovascular disease (CVD) is increasingly common among women with HIV, but literature on nonlipid CVD risk factor management is lacking. We examined semiannual trends from 2006 to 2014 in hypertension treatment and control (blood pressure

BackgroundMarijuana (hereafter "tetrahydrocannabinol [THC]") use has been associated with liver fibrosis progression in retrospective analyses of patients with chronic hepatitis C (HCV). We studied long-term effects of THC on fibrosis progression in women coinfected with human immunodeficiency virus (HIV)/HCV enrolled in the Women's Interagency HIV Study (WIHS).MethodsLiver fibrosis was categorized according to FIB-4 scores as none, moderate, or significant. THC and alcohol use were quantified as average exposure per week. Associations between THC use and progression to significant fibrosis were assessed using Cox proportional hazards regression.ResultsAmong 575 HIV/HCV-coinfected women followed for a median of 11 (interquartile range, 6-17) years, 324 (56%) reported no THC use, 141 (25%) less than weekly use, 70 (12%) weekly use, and 40 (7%) daily use at WIHS entry. In univariable analysis, entry FIB-4 score (hazard ratio [HR], 2.26 [95% confidence interval {CI}, 1.88-2.73], P < .001), log HCV RNA (HR, 1.19 [95% CI, 1.02-1.38], P = .02), tobacco use (HR, 1.37 [95% CI, 1.02-1.85], P = .04), CD4(+) count (risk per 100-cell increase: HR, 0.90 [95% CI, .86-.95], P < .001), and log HIV RNA (HR, 1.18 [95% CI, 1.05-1.32], P = .005) were associated with progression to significant fibrosis, as was cumulative alcohol use in follow-up (HR, 1.03 [95% CI, 1.02-1.04], P < .001). In multivariable analysis, entry FIB-4, entry CD4(+) count, and cumulative alcohol use remained significant. Cumulative THC use was not associated with fibrosis progression (HR, 1.01 [95% CI, .92-1.10], P = .83).ConclusionsIn this large cohort of HIV/HCV-coinfected women, THC was not associated with progression to significant liver fibrosis. Alcohol use was independently associated with liver fibrosis, and may better predict fibrosis progression in HIV/HCV-coinfected women.

ObjectiveCoinfection with hepatitis C virus (HCV) is a major cause of morbidity and mortality among individuals with HIV. Our objective was to assess the prognostic performance of noninvasive measures of liver fibrosis in predicting all-cause mortality in women with HIV/HCV coinfection.DesignWe studied HCV/HIV coinfected women enrolled in the prospective, multicenter Women's Interagency HIV Study. Aspartate aminotransferase to platelet ratio and FIB-4 were used to identify women without fibrosis at all visits and women who progressed to severe fibrosis.MethodsEnhanced liver fibrosis (ELF), which utilizes direct measures of fibrosis, hyaluronic acid, procollagen III aminoterminal peptide and tissue inhibitor of matrix metalloproteinase was performed.ResultsIncluded were 381 women with 2296 ELF measurements, with mean follow-up 8.3 ± 3.3 years. There were 134 deaths (60% with severe liver fibrosis). Receiver operator characteristic curves at fixed time windows prior to death or at end of follow-up showed that ELF was best at predicting mortality when tested within a year of death (area under the curve for ELF 0.85 vs. APRI 0.69, P

ObjectivesHepatitis C virus (HCV) infection causes an alteration in T-cell maturation and activation in patients coinfected with human immunodeficiency virus (HIV). Because interleukin 7 (IL-7) is a major cytokine controlling T-cell homeostasis, we analyzed the potential influence of HCV coinfection on circulating IL-7 levels in HIV-infected women before and after highly active antiretroviral therapy (HAART).Design and methodsThis prospective study included 56 HIV monoinfected, 55 HIV/HCV coinfected without HCV viremia, 132 HIV/HCV coinfected with HCV viremia, and 61 HIV/HCV-uninfected women for whom plasma levels of IL-7 were determined by enzyme-linked immunosorbent assay at 1 or more follow-up visits before and after HAART. Cross-sectional analyses of the associations between plasma IL-7 levels and HCV infection, demographic, clinical, and immunologic characteristics were evaluated using univariate and multivariate linear regression models before and after HAART.ResultsIn multivariate models, IL-7 levels were significantly higher in coinfected HCV viremic women than in HIV monoinfected women (multiplicative effect = 1.48; 95% confidence interval: 1.01 to 2.16; P = 0.04) before HAART, but were similar between these two groups among women after HAART. In addition to HCV viremia, higher IL-7 levels were associated with older age (P = 0.02), lower CD4(+) T-cell count (P = 0.0007), and higher natural killer T-cell count (P = 0.02) in women before HAART. Among HAART-treated women, only lower CD4(+) T-cell count was significantly associated with IL-7 level (P = 0.006).ConclusionsOur data demonstrate that in HIV-infected women, circulating levels of IL-7 are strongly associated with CD4 T-cell depletion both before and after HAART. Our data also demonstrate that HCV viremia increases circulating IL-7 levels before HAART but not after HAART in coinfected women. This suggests that the effect of HCV on lymphopenia is abrogated by HAART.

Suboptimal adherence to antiretroviral (ARV) therapy among HIV-infected individuals is associated with increased risk of progression to AIDS and the development of HIV resistance to ARV medications. To examine whether the luteal phase of the menstrual cycle is independently associated with suboptimal adherence to single tablet regimen (STR) ARV medication, data were analyzed from a multicenter cohort study of HIV-infected women who reported regular menstrual cycles and were taking an STR. In a cross-sectional analysis, suboptimal adherence to an STR among women in their follicular phase was compared with suboptimal adherence among women in their luteal phase. In two-way crossover analyses, whereby the same woman was assessed for STR medication adherence in both her follicular and luteal phases, the estimated exact conditional odds of non-adherence to an STR was measured. In adjusted logistic regression analysis of the cross-sectional data (N=327), women with ≤12 years of education were more than three times more likely to have suboptimal adherence (OR=3.6, p=.04) compared to those with >12 years of education. Additionally, women with Center for Epidemiological Studies Depression Scale (CES-D) scores ≥23 were 2.5-times more likely to have suboptimal adherence (OR=2.6, p=.02) compared to those with CES-D scores

Background.  Subjects on suppressive combination antiretroviral therapy (cART) who do not achieve robust reconstitution of CD4(+) T cells face higher risk of complications and death. We studied participants in the Women's Interagency HIV Study with good (immunological responder [IR]) or poor (immunological nonresponder [INR]) CD4(+) T-cell recovery after suppressive cART (n = 50 per group) to determine whether cytokine levels or low-level viral load correlated with INR status. Methods.  A baseline sample prior to viral control and 2 subsequent samples 1 and 2 years after viral control were tested. Serum levels of 30 cytokines were measured at each time point, and low-level human immunodeficiency virus (HIV) viral load and anti-HIV antibody levels were measured 2 years after viral suppression. Results.  There were minimal differences in cytokine levels between IR and INR subjects. At baseline, macrophage inflammatory protein-3β levels were higher in IR subjects; after 1 year of suppressive cART, soluble vascular endothelial growth factor-R3 levels were higher in IR subjects; and after 2 years of suppressive cART, interferon gamma-induced protein 10 levels were higher in INR subjects. Very low-level HIV viral load and anti-HIV antibody levels did not differ between IR and INR subjects. Conclusions.  These results imply that targeting residual viral replication might not be the optimum therapeutic approach for INR subjects.

Human immunodeficiency virus (HIV) infectivity increases as receptor/coreceptor expression levels increase. We determined peripheral CD4, CCR5, and CXCR4 expression levels in HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA; n = 32), the levonorgestrel-releasing intrauterine device (LNG-IUD; n = 27), oral contraceptive pills (n = 32), or no hormonal contraception (n = 33). The use of LNG-IUD increased the proportion of CD4(+) and CD8(+) T cells that expressed CCR5; increases in the magnitude of T-cell subset CCR5 expression were observed with DMPA and LNG-IUD use (P < .01 for all comparisons). LNG-IUD and, to a lesser extent, DMPA use were associated with increased peripheral T-cell CCR5 expression.

BackgroundWe previously reported that fracture incidence rates did not differ by HIV status among predominantly premenopausal Women's Interagency HIV Study participants. We now conduct a follow-up study with 5 additional observation years to further characterize fracture risk associated with HIV infection in women as they age.MethodsWe measured time to first new fracture at any site in 2375 (1713 HIV-infected and 662 HIV-uninfected) Women's Interagency HIV Study participants, with median 10-year follow-up. Fractures were self-reported semiannually. Proportional hazards models assessed predictors of incident fracture.ResultsAt index visit, HIV-infected women were older [median age of 40 years (IQR: 34-46) vs. 35 (27-43), P < 0.0001] and more likely to be postmenopausal, hepatitis C virus infected, and weigh less than HIV-uninfected women. Among HIV-infected women, mean CD4 count was 480 cells per microliter and 63% were taking highly active antiretroviral therapy. Unadjusted incidence rates of any fracture were higher in HIV-infected than in HIV-uninfected women [2.19/100 person-years (py) vs. 1.54/100 py, P = 0.002]. In multivariate models, HIV status, older age, white (vs. black) race, prior fracture, history of cocaine use, and history of injection drug use were significant predictors of incident fracture. Among HIV-infected women, age, white race, prior fracture, smoking, and prior AIDS were predictors of new fracture.ConclusionsMiddle-aged HIV-infected women had a higher adjusted fracture rate than HIV-uninfected women. Cocaine use and injection drug use were also associated with a greater risk of incident fracture. Further research is needed to understand whether the risk of fracture associated with cocaine use relates to increased rate of falls or direct effects on bone metabolism.

Cognitive impairment (CI) remains common despite access to combination antiretroviral therapy (cART); it has been linked to HIV-specific, HIV-related, and HIV-unrelated factors. Insulin resistance (IR) was associated with CI in the early cART era, when antiretroviral medications had greater mitochondrial and metabolic toxicity. We sought to examine these relationships in the current cART era of reduced antiretroviral toxicities. This study examined IR among non-diabetics in relation to a 1-h neuropsychological test battery among 994 women (659 HIV-infected and 335 HIV-uninfected controls) assessed between 2009 and 2011. The mean (standard deviation (SD)) age of the sample was 45.1 (9.3) years. The HIV-infected sample had a median interquartile range (IQR) cluster of differentiation 4 (CD4) T-lymphocyte count of 502 (310-727) cells/μL, and 54 % had undetectable plasma HIV RNA levels. Among all, the homeostasis model assessment (HOMA) of IR ranged from 0.25 to 37.14. In adjusted models, increasing HOMA was significantly associated with reduced performance on Letter-Number Sequencing (LNS) attention task (β = -0.10, p

We assessed changes in self-reported sexual activity (SA) over 13 years among HIV-infected and uninfected women. The impact of aging and menopause on SA and unprotected anal or vaginal intercourse (UAVI) was examined among women in the Women's Interagency HIV Study (WIHS), stratifying by HIV status and detectable viral load among HIV-infected women. Generalized mixed linear models were fitted for each outcome, adjusted for relevant covariates. HIV-uninfected women evidenced higher levels of SA and UAVI than HIV-infected. The odds of SA declined by 62-64 % per decade of age. The odds of SA in a 6-month interval for women aged 40-57 declined by 18-22 % post-menopause (controlling for age). Among HIV+/detectable women only, the odds of any UAVI decreased by 17 % per decade of age; the odds of UAVI were unchanged pre-menopause, and then decreased by 28 % post-menopause. Elucidating the factors accounting for ongoing unprotected sex among older women should inform interventions.

BackgroundHuman immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks.MethodsUsing data from the North American AIDS Cohort Collaboration for Research and Design from January 2000 to December 2009, we validated 286 incident ESRD cases using abstracted medical evidence of dialysis (lasting >6 months) or renal transplant. A total of 38 354 HIV-infected adults aged 18-80 years contributed 159 825 person-years (PYs). Age- and sex-standardized incidence ratios (SIRs) were estimated by race. Poisson regression was used to identify predictors of ESRD.ResultsHIV-infected ESRD cases were more likely to be of black race, have diabetes mellitus or hypertension, inject drugs, and/or have a prior AIDS-defining illness. The overall SIR was 3.2 (95% confidence interval [CI], 2.8-3.6) but was significantly higher among black patients (4.5 [95% CI, 3.9-5.2]). ESRD incidence declined from 532 to 303 per 100 000 PYs and 138 to 34 per 100 000 PYs over the time period for blacks and nonblacks, respectively, coincident with notable increases in both the prevalence of viral suppression and the prevalence of ESRD risk factors including diabetes mellitus, hypertension, and hepatitis C virus coinfection.ConclusionsThe risk of ESRD remains high among HIV-infected individuals in care but is declining with improvements in virologic suppression. HIV-infected black persons continue to comprise the majority of cases, as a result of higher viral loads, comorbidities, and genetic susceptibility.

ObjectiveT-cell activation is a major pathway driving HIV disease progression. Little is known regarding the impact of T-cell activation on HIV-associated atherosclerosis and cardiovascular disease, a common comorbidity in HIV infection. We hypothesized that T-cell activation will predict vascular stiffness, a measure of subclinical atherosclerosis.DesignLinear regression models evaluated the covariate-adjusted association of T-cell activation with vascular stiffness.MethodsCD38 and HLA-DR expression on CD4⁺ and CD8⁺ T cells was assessed by flow cytometry among 59 HIV-negative and 376 HIV-infected (185 hepatitis C coinfected) women in the Women's Interagency HIV Study. T-cell activation was defined by CD8⁺CD38⁺DR+ and CD4⁺CD3⁺8DR+. Multiple activation assessments over 6.5 years were averaged. In 140 women, T-cell activation was measured before and after highly active antiretroviral therapy (HAART) initiation. Carotid artery ultrasounds were completed a median of 6.5 years after last measurement of T-cell activation and carotid artery stiffness including distensibility and elasticity were calculated.ResultsPercentages of CD4⁺ and CD8⁺ T-cell activation were significantly higher in HIV- infected compared with HIV-negative women. Among HIV-negative women, T-cell activation was not associated with carotid artery stiffness. Among HIV-infected women, higher CD4⁺ T-cell activation levels significantly predicted increased arterial stiffness independent of CD4⁺ cell count and HIV RNA. The association was stronger among HIV/hepatitis C-coinfected women compared with HIV-monoinfected women; however, the difference was not statistically significant (P for interaction >0.05). Pre- and post-HAART levels of CD4⁺ T-cell activation significantly predicted carotid artery stiffness.ConclusionsPersistent T-cell activation, even after HAART initiation, can contribute to structural and/or functional vascular damage accelerating atherogenesis in HIV infection. These results need to be confirmed in a longitudinal prospective study.

: In HIV negatives, markers of hemostasis, including D-dimer, factor VIII, plasminogen activator inhibitor-1 antigen (PAI-1), and total protein S are associated with all-cause and cardiovascular disease mortality. In HIV positives, studies of D-dimer and factor VIII with death were limited to short follow-up; associations of PAI-1 and total protein S with death have not been examined. In 674 HIV-infected women from the Women's Interagency HIV Study, markers from the first visit after enrollment were exposures of interest in multivariate analyses of death (AIDS and non-AIDS) in separate models at 5 and 16 years. There were 87 AIDS and 44 non-AIDS deaths at 5 years, and 159 AIDS and 113 non-AIDS deaths at 16 years. An inverse association of total protein S quartiles with non-AIDS deaths was observed at 5 (P trend = 0.002) and 16 years (P trend = 0.02); there was no association with AIDS deaths. The third quartile of PAI-1 was associated with AIDS deaths at 5 [hazard ratio (HR) = 4.0; 95% confidence interval (CI): 1.9 to 8.4] and 16 years (HR = 3.4; 95% CI: 1.9 to 5.9); and with non-AIDS deaths at 5 years (HR = 4.8; 95% CI: 1.6 to 13.9). D-dimer and factor VIII were not associated with AIDS or non-AIDS death at 5 or 16 years. Lower total Protein S was a consistent marker of non-AIDS death. We found no association between D-dimer with AIDS or non-AIDS death, in contrast to previous studies showing increased short-term (

ObjectiveWe evaluated the separate and interactive associations of menopausal stage, menopausal symptoms, and human immunodeficiency virus (HIV) infection with cognition. We hypothesized that HIV-infected perimenopausal women would show the greatest cognitive difficulties and that menopausal symptoms would be inversely associated with cognition.MethodsThis cross-sectional study included 708 HIV-infected and 278 HIV-uninfected premenopausal, perimenopausal, or postmenopausal women (64% African American; median age, 44 y) from the Women's Interagency HIV Study. Participants completed tests of verbal learning and memory, attention/processing speed, and executive function. We administered a menopausal symptom questionnaire that assessed anxiety, vasomotor, and sleep symptoms and obtained measures of depressive symptoms.ResultsIn multivariable regression analyses controlling for relevant covariates, HIV infection, but not menopausal stage, was associated with worse performance on all cognitive measures (P's < 0.05). Depressive symptoms were associated with lower cognitive performance on measures of verbal learning and memory, attention, and executive function (P's < 0.05); anxiety symptoms were associated with lower performance on measures of verbal learning and memory (P's < 0.05). Vasomotor symptoms were associated with worse attention (P < 0.05). HIV and anxiety symptoms interacted to influence verbal learning (P's < 0.05); elevated anxiety was associated with worse verbal learning in HIV-infected women only.ConclusionsVasomotor, depressive, and anxiety symptoms, but not menopausal stage, are associated with worse cognitive performance in both HIV-infected and HIV-uninfected women, although elevated anxiety symptoms are more associated with verbal learning deficits in HIV-infected women. Because cognitive problems can interfere with everyday functioning, including treatment adherence, it may be important to screen and treat anxiety in HIV-infected women.

ObjectiveInfection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) may be associated with atherosclerosis and vascular disease. Macrophages are a major component of atherosclerotic plaque, and classically activated (M1) macrophages contribute to plaque instability. Our goal was to identify plasma biomarkers that reflect macrophage inflammation and are associated with subclinical atherosclerosis.Approach and resultsWe tested whether M1 macrophages produce galectin-3-binding protein in vitro. Then, we measured galectin-3-binding protein and the soluble macrophage biomarkers soluble cluster of differentiation (CD) 163 and soluble CD14 in 264 participants in the Women's Interagency HIV Study. Women were positive for HIV, HCV, both, or neither (66 in each group, matched for age, race/ethnicity, and smoking status). Carotid artery disease was assessed by ultrasound measurement of right distal common carotid artery intima-media thickness, distensibility, and presence of atherosclerotic lesions (intima-media thickness >1.5 mm). Plasma galectin-3-binding protein was higher in HCV+ than HCV- women (P

Relationships between vitamin D, lipids, HIV infection, and HIV treatment (±antiretroviral therapy [ART]) were investigated with Women's Interagency HIV Study data (n = 1758 middle-aged women) using multivariable regression. Sixty-three percent of women had vitamin D deficiency. Median 25-hydroxyvitamin D (25-OH vitamin D) was highest in HIV-infected + ART-treated women (17 ng/mL; P < .001) and was the same in HIV-uninfected or HIV-infected women without ART (14 ng/mL). Vitamin D levels were lower if efavirenz (EFV) was included in ART (15 versus 19 ng/mL; P < .001). The most common lipid abnormality was high triglycerides (≥200 mg/dL) in HIV-infected + ART-treated women (13% versus 7% of HIV-infected without ART and 5% of HIV-uninfected; P < .001), with a positive relationship between 25-OH vitamin D and triglycerides (95% confidence interval 0.32-1.69; P < .01). No relationships between 25-OH vitamin D and cholesterol were detected. Vitamin D deficiency is common irrespective of HIV status but influenced by HIV treatment. Similarly, vitamin D levels were positively related to triglycerides only in ART-treated HIV-infected women and unrelated to cholesterol.

IntroductionThe use of single-tablet antiretroviral therapy (ART) regimens and its implications on adherence among HIV-infected women have not been well described.MethodsParticipants were enrolled in the Women's Interagency HIV Study, a longitudinal study of HIV infection in US women. We examined semiannual trends in single-tablet regimen use and ART adherence, defined as self-reported 95% adherence in the past 6 months, during 2006-2013. In a nested cohort study, we assessed the comparative effectiveness of a single-tablet versus a multiple-tablet regimen with respect to adherence, virologic suppression, quality of life, and AIDS-defining events, using propensity score matching to account for demographic, behavioral, and clinical confounders. We also examined these outcomes in a subset of women switching from a multiple- to single-tablet regimen using a case-crossover design.ResultsWe included 15,523 person-visits, representing 1727 women (53% black, 29% Hispanic, 25% IDU, median age 47). Use of single-tablet regimens among ART users increased from 7% in 2006% to 27% in 2013; adherence increased from 78% to 85% during the same period (both P < 0.001). Single-tablet regimen use was significantly associated with increased adherence (adjusted risk ratio: 1.05; 95% confidence interval: 1.03 to 1.08) and virologic suppression (risk ratio: 1.06; 95% confidence interval: 1.01 to 1.11), while associations with improved quality of life and fewer AIDS-defining events did not achieve statistical significance. Similar findings were observed among the subset of switchers.ConclusionsSingle-tablet regimen use was associated with increased adherence and virologic suppression. Despite this, 15% of women prescribed ART were still not optimally adherent; additional interventions are needed to maximize therapeutic benefits.

ObjectivesThe introduction of HAART leads to control of HIV replication to less than 50 copies/ml, similar to levels in 'elite controllers'. Low-level viral replication may be one of the contributing factors to persistent immune activation/inflammation in HAART-treated individuals. There are still gaps in our knowledge of whether low-level replication persists in systemic versus mucosal sites.Design and methodsParticipants for this study were recruited from the Women's Interagency HIV Study. We evaluated 33 'elite controllers' who naturally controlled HIV replication and 33 matched HAART-suppressed recipients. This study employed a sensitive target-capture transcription-mediated-amplification assay to compare low-level virus concentrations in plasma and cervical-vaginal lavage (CVL) samples from HIV-positive HAART recipients and 'elite controllers'.ResultsThe median (interquartile range) plasma viral load signal/cut-off (S/Co) for 'elite controllers' was 10.5 (3.9-21.1), which was significantly (P < 0.001) higher than the S/Co for HAART recipients [2.0 (1-4.9)]. The majority of CVL samples from both groups had undetectable HIV RNA and the proportion of CVL samples with a cut-off more than 1.0 was not different between 'elite controllers' and HAART-suppressed recipients.ConclusionThis study demonstrated persistent low-level HIV replication in 'elite controllers', suggesting potential value of HAART treatment for these individuals. Absent or very low levels of HIV RNA in CVL indicate very low risk of secondary sexual transmission for both groups.