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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 Womens 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.

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

BackgroundImmune reconstitution bone loss (IRBL) is a common side-effect of antiretroviral therapy (ART) in people with human immunodeficiency virus (PWH). Immune reconstitution bone loss acts through CD4+ T-cell/immune reconstitution-induced inflammation and is independent of antiviral regimen. Immune reconstitution bone loss may contribute to the high rate of bone fracture in PWH, a cause of significant morbidity and mortality. Although IRBL is transient, it remains unclear whether bone recovers, or whether it is permanently denuded and further compounds bone loss associated with natural aging.MethodsWe used a validated IRBL mouse model involving T-cell reconstitution of immunocompromised mice. Mice underwent cross-sectional bone phenotyping of femur and/or vertebrae between 6 and 20 months of age by microcomputed tomography (µCT) and quantitative bone histomorphometry. CD4+ T cells were purified at 20 months to quantify osteoclastogenic/inflammatory cytokine expression.ResultsAlthough cortical IRBL in young animals recovered with time, trabecular bone loss was permanent and exacerbated skeletal decline associated with natural aging. At 20 months of age, reconstituted CD4+ T cells express enhanced osteoclastogenic cytokines including RANKL, interleukin (IL)-1β, IL-17A, and tumor necrosis factor-α, consistent with elevated osteoclast numbers.ConclusionsImmune reconstitution bone loss in the trabecular compartment is permanent and further exacerbates bone loss due to natural aging. If validated in humans, interventions to limit IRBL may be important to prevent fractures in aging PWH.

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.

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

BackgroundFood insecurity and intimate partner violence (IPV) are associated with suboptimal HIV prevention and treatment outcomes, yet limited research has explored how food insecurity and IPV intersect to influence HIV-related behaviors. To fill this gap, we conducted a qualitative study with women living with or at risk for HIV in the United States.MethodsWe conducted 24 in-depth interviews with women enrolled in the San Francisco and Atlanta sites of the Women's Interagency HIV study (WIHS). Participants were purposively sampled so half were living with HIV and all reported food insecurity and IPV in the past year. Semi-structured interviews explored experiences with food insecurity and IPV, how these experiences might be related and influence HIV risk and treatment behaviors. Analysis was guided by an inductive-deductive approach.ResultsA predominant theme centered on how food insecurity and IPV co-occur with poor mental health and substance use to influence HIV-related behaviors. Women described how intersecting experiences of food insecurity and IPV negatively affected their mental health, with many indicating using substances to "feel no pain". Substance use, in turn, was described to perpetuate food insecurity, IPV, and poor mental health in a vicious cycle, ultimately facilitating HIV risk behaviors and preventing HIV treatment adherence.ConclusionsFood insecurity, IPV, poor mental health and substance use intersect and negatively influence HIV prevention and treatment behaviors. Findings offer preliminary evidence of a syndemic that goes beyond the more widely studied "SAVA" (substance use, AIDS, and violence) syndemic, drawing attention to additional constructs of mental health and food insecurity. Quantitative research must further characterize the extent and size of this syndemic. Policies that address the social and structural drivers of this syndemic, including multi-level and trauma-informed approaches, should be implemented and evaluated to assess their impact on this syndemic and its negative health effects.

Food insecurity, which affects 37 million individuals in the United States (U.S.) and disproportionately burdens women, minorities and older adults, is a well-established determinant of poor health. Previous studies suggest social capital, defined as the material and social benefits arising from relationships among individuals within and between groups, may be protective against food insecurity. Drawing on this evidence, calls have been made for interventions and policies to promote social capital to address food insecurity. However, limited research has explored in-depth how social capital shapes the lived experience of food insecurity in the U.S. We explored how older women from three settings in the U.S. used forms of social capital to navigate their food environments. Between November 2017-July 2018, we conducted 38 semi-structured interviews with food-insecure women aged 50 years or older enrolled in the Northern California, Georgia, and North Carolina sites of the Women's Interagency HIV study, an ongoing cohort study of women living with and at risk of HIV. Interviews were analyzed using an inductive-deductive approach. Women from the three sites explained how they drew upon different forms of capital to access food. Women in Georgia and North Carolina depended on support from members within their social group (bonding social capital) to address food insecurity but described limited opportunities to build relationships with members from other social groups (bridging social capital) or representatives of institutions (linking social capital). In contrast, women from Northern California frequently used bridging and linking social capital to access food but described limited bonding social capital. Findings show how the role of social capital in protecting against food insecurity is diverse, complex, and structurally determined. Intervention implications are discussed.

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.

Food insecurity (FI) contributes to HIV-related morbidity and mortality, but the mechanisms whereby FI negatively impacts HIV health are untested. We tested the hypothesis that FI leads to poor HIV clinical outcomes through nutritional, mental health, and behavioral paths. We analyzed data from Women's Interagency HIV Study (WIHS) among 1803 women living with HIV (WLWH) (8225 person-visits) collected from 2013 to 2015 biannually from nine sites across the United States participating in the WIHS. FI was measured with the US Household Food Security Survey Module. Outcomes included HIV viral nonsuppression, CD4 cell counts, and physical health status (PHS). We used longitudinal logistic and linear regression models with random effects to examine associations adjusting for covariates and path analysis to test nutritional, mental health, and behavioral paths. Increasing severity of FI was associated with unsuppressed viral load, lower CD4 counts, and worse PHS (all p

BackgroundFood insecurity is a well-established determinant of suboptimal, self-reported antiretroviral therapy (ART) adherence, but few studies have investigated this association using objective adherence measures. We examined the association of food insecurity with levels of ART concentrations in hair among women living with human immunodeficiency virus (WLHIV) in the United States.MethodsWe analyzed longitudinal data collected semiannually from 2013 through 2015 from the Women's Interagency HIV Study, a multisite, prospective, cohort study of WLHIV and controls not living with HIV. Our sample comprised 1944 person-visits from 677 WLHIV. Food insecurity was measured using the US Household Food Security Survey Module. ART concentrations in hair, an objective and validated measure of drug adherence and exposure, were measured using high-performance liquid chromatography with mass spectrometry detection for regimens that included darunavir, atazanavir, raltegravir, or dolutegravir. We conducted multiple 3-level linear regressions that accounted for repeated measures and the ART medication(s) taken at each visit, adjusting for sociodemographic and clinical characteristics.ResultsAt baseline, 67% of participants were virally suppressed and 35% reported food insecurity. In the base multivariable model, each 3-point increase in food insecurity was associated with 0.94-fold lower ART concentration in hair (95% confidence interval, 0.89 to 0.99). This effect remained unchanged after adjusting for self-reported adherence.ConclusionsFood insecurity was associated with lower ART concentrations in hair, suggesting that food insecurity may be associated with suboptimal ART adherence and/or drug absorption. Interventions seeking to improve ART adherence among WLHIV should consider and address the role of food insecurity.

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.

Material-need insecurities (including insecurities in basic resources such as income, food, housing, and healthcare) are widespread in the United States (US) and may be important predictors of poor health outcomes. How material-need insecurities besides food insecurity are experienced, however, remains under-researched, including how multiple material-need insecurities might intersect and converge on the individual. Here we used qualitative methods to investigate experiences with multiple material-need insecurities among 38 food-insecure women aged over 50 years living with or at risk for HIV in the US. Our aims were: (1) to understand the co-experience of material-need insecurities beyond food insecurity; (2) to elucidate how multiple material-need insecurities might intersect; and (3) to discover how this intersection might be detrimental to health. During November 2017-July 2018, we conducted semi-structured interviews at three sites across the US (Northern California, Georgia, North Carolina) and analyzed the data using an inductive-deductive approach. We identified a common and complex picture of multiple material-need insecurities, stigma, and illness among participants across all three sites. There were five primary themes: (1) insecure income arising from a combination of precarious wage labor and federal disability benefits; (2) resultant experiences of uncertainty, compromised quality, insufficiency, and having to use socially unacceptable coping strategies across finances, food, housing, and healthcare; (3) participants' disempowerment arising from their engagement with social safety net institutions; (4) closely related experiences of intersectional stigma and discrimination; and (5) negative implications for health across a wide range of illnesses. By employing the sociological concept of precarity-a term denoting the contemporary convergence of insecure wage labor and retraction of the welfare state-we combine these themes into a unifying framework of precarity and health. This framework may prove useful for testing how the widespread intersection of multiple material-need insecurities interacts with stigma and discrimination to negatively impact physical and mental health.

BackgroundFood insecurity, which disproportionately affects marginalized women in the United States, is associated with depressive symptoms. Few studies have examined relations of food insecurity with other mental health outcomes.ObjectiveThe aim of this study was to investigate the associations of food insecurity with symptoms of generalized anxiety disorder (GAD), stress, and posttraumatic stress disorder (PTSD) in the Women's Interagency HIV Study (WIHS), a prospective cohort study of women with or at risk of HIV in the United States.MethodsParticipants were 2553 women with or at risk of HIV, predominantly African American/black (71.6%). Structured questionnaires were conducted during April 2013-March 2016 every 6 mo. Food security (FS) was the primary predictor, measured using the Household Food Security Survey Module. We measured longitudinal outcomes for GAD (GAD-7 score and a binary GAD-7 screener for moderate-to-severe GAD). Only cross-sectional data were available for outcomes measuring perceived stress (PSS-10 score) and PTSD (PCL-C score and a binary PCL-C screener for PTSD). We examined associations of FS with the outcomes through use of multivariable linear and logistic regression, including lagged associations with GAD outcomes.ResultsAfter adjusting for sociodemographic and health-related factors including HIV serostatus, current marginal, low, and very low FS were associated with increasingly higher GAD-7 scores, and with 1.41 (95% CI: 1.10, 1.80; P

BackgroundFood insecurity and mental health negatively affect the lives of women in the United States. Participants in the Women's Interagency HIV Study (WIHS) provided the opportunity to understand the association of food insecurity with depression and mental well-being over time.ObjectiveWe investigated the association between current and persistent food insecurity and depression among women at risk of or living with HIV in the United States.MethodsWe used longitudinal data from the WIHS, a prospective cohort study in women at risk of or living with HIV from multiple sites in the United States. Participants completed 6 semiannual assessments from 2013 to 2016 on food security (FS; high, marginal, low, and very low) and mental health (i.e., depressive symptoms and mental well-being). We used multiple regression analysis to estimate the association between these variables.ResultsAmong 2551 participants, 44% were food insecure and 35% reported depressive symptoms indicative of probable depression. Current marginal, low, and very low FS were associated with 2.1-, 3.5-, and 5.5-point (all P

Background and aimsFew longitudinal studies have examined the relationship between food insecurity and substance use. We aimed to investigate this relationship using longitudinal data among women with or at risk for HIV in the United States.DesignWomen's Interagency HIV Study (WIHS), a prospective cohort study.SettingNine sites across the United States.ParticipantsA total of 2553 women with or at risk for HIV.MeasurementsSemi-annual structured interviews were conducted during April 2013-March 2016. Food security (FS) was the primary predictor, measured using the Household Food Security Survey Module. Outcomes were: any illicit substance use except cannabis; licit or illicit cannabis use; stimulant use (crack, cocaine, or methamphetamine); opioid use (heroin or methadone in a non-prescribed way); and prescription drug misuse (prescription narcotics, amphetamines, or tranquilizers in a non-prescribed way) since the last visit. We used multivariable logistic regression with random effects to examine longitudinal associations of current and previous FS with the outcomes simultaneously, adjusting for socio-demographic factors, HIV serostatus, physical health and health insurance.FindingsAverage number of visits was 4.6. At baseline, 71% of participants were HIV-seropositive, 44% reported marginal, low, or very low FS, and 13% were using illicit substances. In adjusted analyses, current low and very low FS were significantly associated with 1.59 [95% confidence interval (CI) = 1.02, 2.46; P = 0.039] and 2.48 (95% CI = 1.52, 4.04; P

BACKGROUND:Food insecurity and violence are two major public health issues facing U.S. women. The link between food insecurity and violence has received little attention, particularly regarding the temporal ordering of events. The present study used data from the Women's Interagency Human Immunodeficiency Virus Study to investigate the longitudinal association of food insecurity and violence in a cohort of women at risk for or living with HIV. METHODS:Study participants completed six assessments from 2013-16 on food insecurity (operationalized as marginal, low, and very low food security) and violence (sexual or physical, and psychological). We used multi-level logistic regression, controlling for visits (level 1) nested within individuals (level 2), to estimate the association of experiencing violence. RESULTS:Among 2,343 women (8,528 visits), we found that victims of sexual or physical violence (odds ratio = 3.10; 95% confidence interval: 1.88, 5.19) and psychological violence (odds ratio = 3.00; 95% confidence interval: 1.67, 5.50) were more likely to report very low food security. The odds of experiencing violence were higher for women with very low food security at both the current and previous visit as compared to only the current visit. HIV status did not modify these associations. CONCLUSIONS:Food insecurity was strongly associated with violence, and women exposed to persistent food insecurity were even more likely to experience violence. Food programs and policy must consider persistent exposure to food insecurity, and interpersonal harms faced by food insecure women, such as violence.

Food insecurity, internalized HIV stigma, and depressive symptoms are independently associated with poor HIV outcomes. Food insecurity, stigma, and depression may be interrelated among women living with HIV (WLHIV). We hypothesized that food insecurity would be independently associated with internalized stigma and depressive symptoms among WLHIV in the United States (US), and would partially account for associations between stigma and depressive symptoms. We tested hypotheses using regression models and partial correlation analysis with cross-sectional data among 1317 WLHIV from the Women's Interagency HIV Study. In adjusted models, greater food insecurity was associated with internalized HIV stigma and depressive symptoms (all p

BackgroundThis study investigates the association of clinical and demographic predictors with abdominal fat gain, measured using waist circumference (WC) and self-reported abdominal size.MethodsWe analyzed data from ACTG A5257, a clinical trial that randomized treatment-naïve HIV-infected participants to 1 of 3 antiretroviral regimens: raltegravir (RAL) or the protease inhibitors (PIs) atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r), each in combination with tenofovir disoproxil fumarate/emtricitabine. Associations of treatment and baseline/demographic characteristics with 96-week WC change were assessed using repeated-measures models. Ordinal logistic regression was used to examine the associations of predictors with week 96 self-reported abdominal changes.ResultsThe study population (n = 1809) was 76.0% male and predominantly black non-Hispanic (41.9%) and white non-Hispanic (34.1%). Mean baseline WC was 90.6 cm, with an average 96-week increase of 3.4 cm. WC increases were higher in the RAL arm compared with DRV/r (P = .0130). Females experienced greater increases in WC on RAL vs ATV/r than males (P = .0065). Similarly, a larger difference in WC change was found for RAL vs DRV/r for black vs nonblack individuals (P = .0043). A separate multivariable model found that in addition to the treatment regimen, higher baseline viral load and lower CD4+ were also associated with WC increases.ConclusionsWith antiretroviral therapy initiation, higher WC increases in the RAL arm compared with PIs were more pronounced in female and black participants, and a more advanced baseline HIV disease state was a strong predictor of larger abdominal increases. Understanding factors predisposing individuals to abdominal fat gain could inform health management after therapy initiation.

Vaccine-preventable diseases (VPDs) pose a serious public health concern for people living with HIV (PLH). PLH experience a delayed and weakened response to many vaccines available, compared to the general population. Lower seroconversion rates, along with a decreased efficacy and durability of vaccines, increases the susceptibility of PLH to VPDs. Vaccination guidelines specifically targeting this population have been modified to overcome these challenges. However, vaccine uptake remains suboptimal due to multiple barriers, highlighting the need for further studies and the additional implementation of public health measures specifically tailored to PLH. [ABSTRACT FROM AUTHOR]

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.

BackgroundWe examined whether waist circumference (WC) and self-reported abdominal size changes can estimate visceral adipose tissue (VAT) changes for those initiating antiretroviral therapy (ART).MethodsProspectively collected data from ACTG A5257 and its metabolic substudy, A5260s, were used for this analysis. ART-naive HIV-infected participants were randomized to one of three contemporary ART regimens. Changes in abdominal CT-measured VAT and total adipose tissue (TAT) and DXA-measured trunk fat were tested for association with WC changes (by Pearson correlation) and categories of self-reported abdominal size changes (by ANOVA) between entry and week 96. Linear models compared WC and self-reported changes.ResultsThe study population (n=328) was predominantly male (90%) and White non-Hispanic (44%) with a baseline median age of 36 years and body mass index of 25 kg/m2. At week 96, median WC change was +2.8 cm. Of those reporting at week 96, 53% indicated 'no change/lost', 39% 'gained some/somewhat larger' and 8% 'gained a lot/much larger' as their self-reported changes. Trunk fat, VAT and TAT changes differed across self-reported groups (ANOVA P

Background.  Some patients are not prescribed atazanavir because of concern about possible jaundice. Atazanavir-associated hyperbilirubinemia correlates with UGT1A1 rs887829 genotype. We examined bilirubin-related discontinuation of atazanavir in participants from AIDS Clinical Trials Group Study A5257. Methods.  Discriminatory properties of UGT1A1 T/T genotype for predicting bilirubin-related atazanavir discontinuation through 96 weeks after antiretroviral initiation were estimated. Results.  Genetic analyses involved 1450 participants, including 481 who initiated randomized atazanavir/ritonavir. Positive predictive values of rs887829 T/T for bilirubin-related discontinuation of atazanavir (with 95% confidence intervals [CIs]) were 20% (CI, 9%-36%) in Black, 60% (CI, 32%-84%) in White, and 29% (CI, 8%-58%) in Hispanic participants; negative predictive values were 97% (CI, 93%-99%), 95% (CI, 90%-98%), and 97% (CI, 90%-100%), respectively. Conclusions.  Bilirubin-related discontinuation of atazanavir was rare in participants not homozygous for rs887829 T/T, regardless of race or ethnicity. We hypothesize that the higher rate of discontinuation among White participants homozygous for rs887829 T/T may reflect differences in physical manifestations of jaundice by race and ethnicity. Selective avoidance of atazanavir initiation among individuals with T/T genotypes would markedly reduce the likelihood of bilirubin-related discontinuation of atazanavir while allowing atazanavir to be prescribed to the majority of individuals. This genetic association will also affect atazanavir/cobicistat.

BackgroundMetabolic effects following combination antiretroviral therapy (cART) vary by regimen type. Changes in metabolic effects were assessed following cART in the AIDS Clinical Trials Group (ACTG) A5257 study, and correlated with plasma ritonavir trough concentrations (C24).MethodsTreatment-naive adult subjects were randomized to ritonavir-boosted atazanavir or darunavir, or raltegravir-based cART. Changes in lipids and other metabolic outcomes over time were estimated. Differences between arms were estimated with 97.5% confidence intervals and compared using pairwise Student t tests. Associations between ritonavir C24 and lipid changes at week 48 were evaluated via linear regression.ResultsAnalyses included 1797 subjects with baseline fasting data. Baseline lipid profiles and metabolic syndrome rates (approximately 21%) were similar across arms. Comparable increases occurred in total cholesterol, triglycerides, and low-density lipoprotein cholesterol with the boosted protease inhibitors (PIs); each PI had greater increases relative to raltegravir (all P ≤ .001 at week 96). Metabolic syndrome incident rates by week 96 (approximately 22%) were not different across arms. Ritonavir C24 was not different by arm (P = .89) (median, 69 ng/mL and 74 ng/mL in the atazanavir and darunavir arms, respectively) and were not associated with changes in lipid measures (all P > .1).ConclusionsRaltegravir produced the most favorable lipid profile. Metabolic syndrome rates were high at baseline and increased to the same degree in all arms. Ritonavir C24 was not different in the PI arms and had no relationship with the modest but comparable increases in lipids observed with either atazanavir or darunavir. The long-term clinical significance of the lipid changes noted with the PIs relative to raltegravir deserves further evaluation.Clinical trials registrationNCT 00811954.

BackgroundNonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy is not suitable for all treatment-naive HIV-infected persons.ObjectiveTo evaluate 3 nonnucleoside reverse transcriptase inhibitor-sparing initial antiretroviral regimens to show equivalence for virologic efficacy and tolerability.DesignA phase 3, open-label study randomized in a 1:1:1 ratio with follow-up for at least 96 weeks. (ClinicalTrials.gov: NCT00811954).Setting57 sites in the United States and Puerto Rico.PatientsTreatment-naive persons aged 18 years or older with HIV-1 RNA levels greater than 1000 copies/mL without resistance to nucleoside reverse transcriptase inhibitors or protease inhibitors.InterventionAtazanavir, 300 mg/d, with ritonavir, 100 mg/d; raltegravir, 400 mg twice daily; or darunavir, 800 mg/d, with ritonavir, 100 mg/d, plus combination emtricitabine, 200 mg/d, and tenofovir disoproxil fumarate, 300 mg/d.MeasurementsVirologic failure, defined as a confirmed HIV-1 RNA level greater than 1000 copies/mL at or after 16 weeks and before 24 weeks or greater than 200 copies/mL at or after 24 weeks, and tolerability failure, defined as discontinuation of atazanavir, raltegravir, or darunavir for toxicity. A secondary end point was a combination of virologic efficacy and tolerability.ResultsAmong 1809 participants, all pairwise comparisons of incidence of virologic failure over 96 weeks showed equivalence within a margin of equivalence defined as -10% to 10%. Raltegravir and ritonavir-boosted darunavir were equivalent for tolerability, whereas ritonavir-boosted atazanavir resulted in a 12.7% and 9.2% higher incidence of tolerability discontinuation than raltegravir and ritonavir-boosted darunavir, respectively, primarily because of hyperbilirubinemia. For combined virologic efficacy and tolerability, ritonavir-boosted darunavir was superior to ritonavir-boosted atazanavir, and raltegravir was superior to both protease inhibitors. Antiretroviral resistance at the time of virologic failure was rare but more frequent with raltegravir.LimitationThe trial was open-label, and ritonavir was not provided.ConclusionOver 2 years, all 3 regimens attained high and equivalent rates of virologic control. Tolerability of regimens containing raltegravir or ritonavir-boosted darunavir was superior to that of the ritonavir-boosted atazanavir regimen.Primary funding sourceNational Institute of Allergy and Infectious Diseases.