The Impact of Childhood Adversity on Life Course Alcohol Use Patterns and Health Status Among People Living with HIV.

Adverse childhood experiences (ACEs) and financial hardship are associated with increased likelihood of heavier alcohol use and health challenges in adulthood among persons living with HIV (PWH). We examined whether retrospectively captured lifetime drinking trajectories are a pathway through which childhood hardships affect current health in a sample of 365 adult PWH. Childhood economic hardship and ACEs were used as main predictors. Measures of alcohol use included age at first drink and lifetime drinking trajectories. Health indicators included health-related quality of life, frailty, number of comorbidities, and symptoms of anxiety, depression, and post-traumatic stress disorder (PTSD). Structural equation modeling (SEM) was applied to estimate both direct and indirect pathways between childhood hardship and physical and mental health. Participants were mostly male; Black (84%); and averaged 48 years of age. SEM results supported both direct and indirect pathways between childhood experiences and adult health. ACEs were connected to physical health directly and mental health both directly and indirectly through age at first drink and drinking heaviness during ages 10-20. Childhood economic hardship related to mental health indirectly through higher drinking levels during ages 10-20. Childhood adverse experiences, economic hardship, and early drinking patterns appear to accumulate, resulting in later life physical and mental health concerns for PWH. Findings support taking a life course approach to health. This includes considering individual trauma histories in HIV care engagement and taking preventative approaches which support the economic and social well-being of vulnerable children to improve health in subsequent decades.

An aerobic exercise intervention to improve metabolic health among people living with HIV with at-risk alcohol use: the ALIVE-Ex research study protocol.

BACKGROUND: Effective antiretroviral therapy (ART) in people living with HIV (PLWH) has improved life expectancy and increased risk of age-associated cardiometabolic comorbidities. At-risk alcohol use is more frequent among PLWH and increases the risk of health challenges. PLWH with at-risk alcohol use are more likely to meet criteria for prediabetes/diabetes and this is associated with impaired whole-body glucose-insulin dynamics. METHODS: The Alcohol & Metabolic Comorbidities in PLWH: Evidence Driven Interventions Study (ALIVE-Ex Study, NCT03299205) is a longitudinal, prospective, interventional study to determine the effects of an aerobic exercise protocol on improving dysglycemia among PLWH with at-risk alcohol use. The intervention is a moderate intensity aerobic exercise protocol implemented 3 days per week for 10 weeks at the Louisiana State University Health Sciences Center-New Orleans. Participants who have a fasting blood glucose level between 94 and 125 mg/dl will be enrolled in the study. Oral glucose tolerance tests, fitness assessments, and skeletal muscle biopsies will be performed pre- and post-exercise intervention. The primary outcome is to determine whether the exercise protocol improves measures of whole-body glucose-insulin dynamics, cardiorespiratory fitness, and skeletal muscle metabolic and bioenergetic function. Secondary outcomes are to determine whether the exercise intervention improves cognitive function and overall quality of life. Results generated will demonstrate the effect of exercise on glycemic measures in PLWH with subclinical dysglycemia and at-risk alcohol use. CONCLUSIONS: The proposed intervention will also have the potential to be scalable to promote lifestyle changes among PLWH, particularly in underserved communities.

Interprofessional education as a potential foundation for future team-based prevention of alcohol use disorder.

BACKGROUND: Effective screening of alcohol use and prevention of alcohol use disorder (AUD) requires the continuous preparation of educated and confident providers across all health professions who will ideally work in close collaboration in their future practices. As one mechanism for achieving this goal, the development and provision of interprofessional education (IPE) training modules for health care students may cultivate beneficial interactions among future health providers early in their formative education. METHODS: In the present study, we assessed attitudes about alcohol and confidence in screening and AUD prevention in 459 students at our health sciences center. Students represented ten different health professions (audiology, cardiovascular sonography, dental hygiene, dentistry, medicine, nursing, physical therapy, public health, respiratory therapy, and speech language pathology programs). For purposes of this exercise, students were divided into small, professionally diverse teams. Responses to ten survey questions (Likert scale) were collected via a web-based platform. These assessments were collected before and after a case-based exercise that provided information to students on the risks of excessive alcohol use as well as the effective screening and team-based management of individuals susceptible to AUD. RESULTS: Wilcoxon signed-rank analyses revealed that the exercise led to significant decreases in stigma toward individuals engaging in at-risk alcohol use. We also discovered significant increases in self-reported knowledge and confidence in personal qualifications needed to initiate brief interventions to reduce alcohol use. Focused analyses of students from individual health programs uncovered unique improvements according to question theme and health profession. CONCLUSION: Our findings demonstrate the utility and effectiveness of single, focused IPE-based exercises to impact personal attitudes and confidence in young health professions learners. While additional longitudinal cohort follow-up studies are needed, these results may translate into more effective and collaborative AUD treatment in future clinical settings.

Unique circulating microRNA associations with dysglycemia in people living with HIV and alcohol use.

People living with HIV (PLWH) have increased prevalence of comorbid conditions including insulin resistance and at-risk alcohol use. Circulating microRNAs (miRs) may serve as minimally invasive indicators of pathophysiological states. We aimed to identify whether alcohol modulates circulating miR associations with measures of glucose/insulin dynamics in PLWH. PLWH (n = 96; 69.8% males) enrolled in the Alcohol & Metabolic Comorbidities in PLWH: Evidence-Driven Interventions (ALIVE-Ex) study were stratified into negative phosphatidylethanol (PEth < 8 ng/mL, n = 42) and positive PEth (PEth ≥ 8 ng/mL, n = 54) groups. An oral glucose tolerance test (OGTT) was administered, and total RNA was isolated from fasting plasma to determine absolute miR expression. Circulating miRs were selected based on their role in skeletal muscle (miR-133a and miR-206), pancreatic ß-cell (miR-375), liver (miR-20a), and adipose tissue (miR-let-7b, miR-146a, and miR-221) function. Correlation and multiple regression analyses between miR expression and adiponectin, 2 h glucose, insulin, and C-peptide values were performed adjusting for body mass index (BMI) category, age, sex, and viral load. miR-133a was negatively associated with adiponectin (P = 0.002) in the negative PEth group, and miR-20a was positively associated with 2 h glucose (P = 0.013) in the positive PEth group. Regression analyses combining miRs demonstrated that miR-133a (P < 0.001) and miR-221 (P = 0.010) together predicted adiponectin in the negative PEth group. miR-20a (P < 0.001) and miR-375 (P = 0.002) together predicted 2 h glucose in the positive PEth group. Our results indicate that associations between miRs and measures of glucose/insulin dynamics differed between PEth groups, suggesting that the pathophysiological mechanisms contributing to altered glucose homeostasis in PLWH are potentially modulated by alcohol use.

Alcohol use, physical activity, and muscle strength moderate the relationship between body composition and frailty risk among people living with HIV.

BACKGROUND: Antiretroviral therapy has improved life expectancy among people living with HIV (PLWH). Despite increased longevity, PLWH are at increased risk of age-related comorbidities, including frailty. We examined the relationship between body composition and frailty among PLWH, and moderation of this relationship by substance use, physical activity (PA), and physical function. METHODS: Participants (n = 341; 71% male, 48 ± 10 years, body mass index (BMI) = 27.3 ± 7.0 kg/m2 ) enrolled in the New Orleans Alcohol Use in HIV (NOAH) study underwent measures of body composition, muscle strength, and gait speed. Whole blood phosphatidylethanol (PEth) was measured, and substance use and PA were self-reported. Frailty risk measures included the 58-Item Deficit Index (DI58) and the Veterans Aging Cohort Study (VACS) Index 1.0, where higher scores indicate greater frailty risk. RESULTS: Multivariable linear regression adjusted for age, sex, and race showed that higher fat-free mass index (FFMI), body fat (%), waist-to-hip ratio, and body mass index (BMI) ≥ 25.0 kg/m2 vs. < 25.0 kg/m2 were significantly (p < 0.05) associated with decreased frailty risk measured by the VACS Index, whereas adjusted analyses showed no association between body composition variables and the DI58 score. Recent alcohol use, muscle strength, and PA, but not lifetime alcohol use or gait speed, significantly moderated associations between body composition variables and frailty risk with medium-to-large effect sizes. Subgroup analyses revealed a negative relationship between DI58 and FFMI among people with PEth > 8 ng/ml and negative relationships of VACS Index with FFMI and WHR in people with lower muscle strength. Overweight or obese BMI categories were positively associated with DI58 in people with lower muscle strength or higher PA level but negatively associated in those with higher muscle strength. CONCLUSIONS: Our findings indicate that body composition has significant modulatory effects on frailty risk in PLWH, where obesity increases the risk of frailty and greater muscle mass may be protective, even in individuals who use alcohol. These results highlight the importance of considering body composition, physical activity, and physical function in assessing frailty risk in PLWH, particularly among individuals who use alcohol. Moreover, they support the implementation of physical activity interventions to ameliorate the risk of frailty in aging PLWH.

Associations of Binge Drinking and Heavy Alcohol Use on Sugar and Fat Intake in a Cohort of Southern People Living with HIV.

AIMS: To assess whether binge drinking and heavy alcohol use are associated with increased sugar and fat consumption among a Southern cohort of people living with HIV (PWH). METHODS: This was a cross-sectional analysis of PWH enrolled in the New Orleans Alcohol use in HIV (NOAH) Study (n = 215). Binge and heavy drinking were identified through a 30-day Alcohol Timeline-Followback and dietary intake was assessed through a 24-hour dietary recall. RESULTS: Participants were 65.4% male, 83.3% Black, with a mean age of 49.2 ± 9.9. Heavy drinkers consumed more total calories than abstainers (P = 0.035) and low-to-moderate drinkers (P = 0.024), and binge drinkers consumed more calories than non-binge drinkers (P = 0.025). Binge and heavy drinkers had significantly higher intake of total and saturated fat in grams. However, substantially increased caloric intake among these participants led to non-significant associations for alcohol use with high total and saturated fat intake as a percent of total energy intake (%TEI). Binge drinkers had lower odds of consuming high sugar as a %TEI (odds ratio: 0.31 [0.14, 0.68]). Additionally, sugar intake predicted total and saturated fat intake, and this association was slightly higher among binge drinkers (total fat P-value: 0.12). CONCLUSIONS: In this population of PWH, while binge and heavy drinking predicted higher caloric and fat intake in grams, binge drinkers were less likely to consume a high-sugar diet. This analysis suggests that interventions focused on reduced alcohol use may be especially beneficial in reducing metabolic disease burden in PWH if supplemented with information on incorporating lower energy-dense foods with reduced fat.

Skeletal muscle bioenergetic health and function in people living with HIV: association with glucose tolerance and alcohol use.

At-risk alcohol use is prevalent and increases dysglycemia among people living with human immunodeficiency virus (PLWH). Skeletal muscle (SKM) bioenergetic dysregulation is implicated in dysglycemia and type 2 diabetes. The objective of this study was to determine the relationship between at-risk alcohol, glucose tolerance, and SKM bioenergetic function in PLWH. Thirty-five PLWH (11 females, 24 males, age: 53 ± 9 yr, body mass index: 29.0 ± 6.6 kg/m2) with elevated fasting glucose enrolled in the ALIVE-Ex study provided medical history and alcohol use information [Alcohol Use Disorders Identification Test (AUDIT)], then underwent an oral glucose tolerance test (OGTT) and SKM biopsy. Bioenergetic health and function and mitochondrial volume were measured in isolated myoblasts. Mitochondrial gene expression was measured in SKM. Linear regression adjusting for age, sex, and smoking was performed to examine the relationship between glucose tolerance (2-h glucose post-OGTT), AUDIT, and their interaction with each outcome measure. Negative indicators of bioenergetic health were significantly (P < 0.05) greater with higher 2-h glucose (proton leak) and AUDIT (proton leak, nonmitochondrial oxygen consumption, and bioenergetic health index). Mitochondrial volume was increased with the interaction of higher 2-h glucose and AUDIT. Mitochondrial gene expression decreased with higher 2-h glucose (TFAM, PGC1B, PPARG, MFN1), AUDIT (MFN1, DRP1, MFF), and their interaction (PPARG, PPARD, MFF). Decreased expression of mitochondrial genes were coupled with increased mitochondrial volume and decreased bioenergetic health in SKM of PLWH with higher AUDIT and 2-h glucose. We hypothesize these mechanisms reflect poorer mitochondrial health and may precede overt SKM bioenergetic dysregulation observed in type 2 diabetes.

Alcohol use and dysglycemia among people living with human immunodeficiency virus (HIV) in the Alcohol & Metabolic Comorbidities in PLWH: Evidence Driven Interventions (ALIVE-Ex) study.

BACKGROUND: At-risk alcohol use is a common and costly form of substance misuse that is highly prevalent among people living with HIV (PLWH). The goal of the current analysis was to test the hypothesis that PLWH with at-risk alcohol use are more likely to meet the clinical criteria for prediabetes/diabetes than PLWH with low-risk alcohol use. METHODS: A cross-sectional analysis was performed on measures of alcohol and glycemic control in adult PLWH (n = 105) enrolled in a prospective, interventional study (the ALIVE-Ex Study (NCT03299205)) that investigated the effects of aerobic exercise on metabolic dysregulation in PLWH with at-risk alcohol use. The Alcohol Use Disorders Identification Test (AUDIT), Timeline Followback, and phosphatidylethanol (PEth) level were used to measure alcohol use. Participants were stratified into low-risk (AUDIT score < 5) and at-risk alcohol use (AUDIT  score ≥ 5). All participants underwent an oral glucose tolerance test and measures of glycemic control- the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Matsuda Index - were correlated with alcohol measures and compared by AUDIT score group using mixed-effects linear and logistic regression models, adjusting for age, sex, race, body mass index (BMI), and viral load. RESULTS: In response to the glucose challenge, participants with at-risk alcohol use (n = 46) had higher glucose levels and were five times more likely to meet criteria for prediabetes/diabetes (OR: 5.3 (1.8, 15.9)) than participants with an AUDIT score < 5. Two-hour glucose values were positively associated with AUDIT score and PEth level and a higher percentage of PLWH with at-risk alcohol use had glucose values ≥140 mg/dl than those with low-risk alcohol use (34.8% vs. 10.2%, respectively). CONCLUSION: In this cohort of PLWH, at-risk alcohol use increased the likelihood of meeting the clinical criteria for prediabetes/diabetes (2-h glucose level ≥140 mg/dl). Established determinants of metabolic dysfunction (e.g., BMI, waist-hip ratio) were not associated with greater alcohol use and dysglycemia, suggesting that other mechanisms may contribute to the impaired glycemic control observed in this cohort.

Factors associated with phosphatidylethanol (PEth) sensitivity for detecting unhealthy alcohol use: An individual patient data meta-analysis.

BACKGROUND: Objective measurement of alcohol consumption is important for clinical care and research. Adjusting for self-reported alcohol use, we conducted an individual participant data (IPD) meta-analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self-reporting unhealthy alcohol consumption. METHODS: We identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1-step IPD meta-analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index-BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger-prick blood collection) variables with PEth sensitivity (PEth≥8 ng/ml), adjusting for the level of self-reported alcohol use using the AUDIT-C score. RESULTS: One third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8 ng/ml) was 81.8%. After adjusting for AUDIT-C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables. CONCLUSIONS: Among people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.

Perspectives Against Racism: educational and socialization efforts at the departmental level.

The current heightened social awareness and anxiety triggered by escalating violence against Black Americans in the United States demands a safe space for reflection, education, and civil discourse within the academic setting. Too often there is an unmet need paired with a collective urgent desire to better understand the chronic existing structural, social, educational, and health inequities affecting disadvantaged populations, particularly Black Americans. In this perspective, the authors provide insight into a shared learning approach that provided a forum to discuss Perspectives Against Racism (PAR). Unlike existing top-down approaches, faculty, trainees, and staff were engaged in leading a series of focused discussions to examine unconscious bias, promote awareness of implicit biases, and reflect on individual and collective roles and responsibilities in working toward becoming antiracist. An existing 1-h graduate elective seminar course was dedicated to creating a space for learning, discussion, and exchange of ideas related to the experience and existence of racism (personal and institutional/systemic). A goal of each session was to go beyond didactics and identify mechanisms to implement change, at the level of the individual, department, and institution. This perspective of the shared experience may provide an adaptable framework that can be implemented in an academic setting at the departmental, center, or institutional level.

Comprehensive Assessment of Alcohol Consumption in People Living with HIV (PLWH): The New Orleans Alcohol Use in HIV Study.

BACKGROUND: High frequency of alcohol use among people living with HIV (PLWH) warrants careful assessment and screening to better understand its impact on HIV disease progression and development of comorbidities. Due to the limitations of the tools used to measure alcohol use, the links to health consequences are not fully understood. METHODS: We completed a cross-sectional analysis to examine the prevalence of alcohol consumption using multiple alcohol assessment tools and their correlation and consistency in a cohort of PLWH (N = 365) enrolled in the New Orleans Alcohol Use in HIV (NOAH) Study. Alcohol use was assessed with the Alcohol Use Disorders Identification Test (AUDIT), timeline followback (TLFB) Calendar, lifetime drinking history, Alcohol and Drug Addiction Severity Index, and blood levels of phosphatidylethanol (PEth). Spearman's correlations were estimated for continuous measures of alcohol consumption; Wilcoxon rank-sum tests were used to compare means; and logistic regression was used to estimate odds of alcohol use by demographic characteristics. RESULTS: Self-report of current alcohol use varied from 58.9 to 73.7% depending on the assessment. All the self-reported alcohol measures showed statistically significant correlations with the biological marker PEth. The highest correlation was with TLFB grams (r = 0.67, p < 0.001). Using TLFB, 73.7% of the cohort reported using alcohol in the last 30 days, and 61.6% had a positive PEth value. The prevalence of risky drinkers, meeting the TLFB > 3 (women) or >4 (men) drinks/day or>7 (women) or>14 (men) drinks/week, was 49.0%. Medium-risk drinking defined as an AUDIT score ≥ 8 was reported in 40.3%, and high-risk drinkers/probable AUD (AUDIT score ≥ 16) was met by 17.0% of the cohort. CONCLUSIONS: Our results demonstrate the importance of comprehensive assessments for alcohol use, including self-report via multiple assessment tools administered by trained staff, as well as the addition of biomarkers for improved classification of subjects into different drinking categories.

Adverse Childhood Experiences, Smoking and Alcohol Use, and Allostatic Load Among People Living with HIV.

Allostatic load is an indicator of multisystem physiologic dysregulation that may arise from prolonged or accumulated exposure to stress, including adverse childhood experiences (ACEs) and chronic stressors persisting into adulthood. People living with HIV (PLWH) may be particularly vulnerable given their high burdens of adversity across the life course. Using data from a cohort of middle aged PLWH, we examined associations between ACEs and two measures of allostatic load. In order to determine whether the negative impact of ACEs on allostatic load operates through increasing the adoption of adverse coping behaviors, we tested for mediation by smoking and alcohol use. PLWH who had experienced 4 or more ACEs had on average higher allostatic load in adulthood compared to those who experienced fewer. Neither smoking nor alcohol use mediated this relationship, however, suggesting alternative mechanisms may be at play.

Associations of Liver Disease with Alcohol Use among People Living with HIV and the Role of Hepatitis C: The New Orleans Alcohol Use in HIV Study.

AIM: This cross-sectional analysis of the New Orleans Alcohol Use in HIV (NOAH) study assesses whether current and lifetime alcohol use in people living with HIV (PLWH) are associated with greater liver disease and how hepatitis C-viral (HCV) co-infection (HIV/HCV+) modifies the association. METHODS: Alcohol use was measured by Lifetime Drinking History (LDH), a 30-day Timeline Followback calendar, the Alcohol Use Disorder Identification Test, and phosphatidylethanol. Liver disease was estimated by alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST platelet ratio-index (APRI), fibrosis-4 index (FIB-4) and nonalcoholic fatty liver disease-fibrosis score. Associations between alcohol consumption and liver disease were estimated with multivariable logistic regression. Models were adjusted for age, sex, body-mass index, hepatitis B and HIV viral load. RESULTS: Participants (N = 353) were majority male (69%) and black (84%) with a mean age of 48.3 ± 10 years. LDH was significantly associated with advanced liver fibrosis (FIB-4 aOR = 22.22 [1.22-403.72]) only among HIV/HCV+ participants with an LDH of 100-600 kg. HIV/HCV+ participants had a higher prevalence of intermediate and advanced liver disease markers than HIV/HCV- (P < 0.0001). Advanced markers of liver disease were most strongly associated with hazardous drinking (≥40(women)/60(men) grams/day) (APRI aOR = 15.87 (3.22-78.12); FIB-4 aOR = 6.76 (1.81-7.16)) and PEth ≥400 ng/ml (APRI aOR = 17.52 (2.55-120.54); FIB-4 aOR = 17.75 (3.30-95.630). CONCLUSION: Results indicate a greater association of current alcohol use with liver disease than lifetime alcohol use, which varied by HCV status. These findings stress the importance of reducing alcohol use in PLWH to decrease risk of liver disease and fibrosis.

Reduced Serum Osteocalcin in High-Risk Alcohol Using People Living With HIV Does Not Correlate With Systemic Oxidative Stress or Inflammation: Data From the New Orleans Alcohol Use in HIV Study.

BACKGROUND: HIV infection is now largely a chronic condition as a result of the success of antiretroviral therapy. However, several comorbidities have emerged in people living with HIV (PLWH), including alcohol use disorders and musculoskeletal disorders. Alcohol use has been associated with lower bone mineral density, alterations to circulating bone turnover markers, and hypocalcemia. The pathophysiological basis of bone loss in the PLWH population is unclear but has been suggested to be linked to oxidative stress and inflammation. To test the hypothesis that PLWH consuming excessive alcohol have altered markers of bone turnover and/or calcium homeostasis in association with oxidative stress, we correlated measurements of alcohol consumption with markers of oxidative stress and inflammation, serum calcium concentrations, and measurements of bone turnover, including c-terminal telopeptide cross-links (CTX-1) and osteocalcin. METHODS: Data were drawn from cross-sectional baseline data from the ongoing New Orleans Alcohol Use in HIV (NOAH) study, comprised of 365 in care PLWH. Alcohol consumption measures (Alcohol Use Disorders Test, 30-day timeline follow-back calendar, and phosphatidylethanol [PEth]) were measured in a subcohort of 40 subjects selected based on highest and lowest PEth measurements. Multivariate linear regression was performed to test the relationships between alcohol consumption and systemic oxidative stress (4-hydroxynonenal; 4-HNE) and inflammation (c-reactive protein; CRP). RESULTS: Serum calcium and CTX-1 did not differ significantly between the high and low-PEth groups. Individuals in the high-PEth group had significantly lower serum osteocalcin (median low-PEth group: 13.42 ng/ml, inter-quartile range [IQR] 9.26 to 14.99 ng/ml; median high-PEth group 7.39 ng/ml, IQR 5.02 to 11.25 ng/ml; p = 0.0005, Wilcoxon rank-sum test). Osteocalcin negatively correlated with PEth (Spearman r = -0.45, p = 0.05) and self-reported measures after adjusting for covariates. Alcohol consumption showed mild, but significant, positive associations with serum 4-HNE, but not with CRP. Osteocalcin did not correlate with either 4-HNE or CRP. CONCLUSIONS: In this subcohort of PLWH, we detected significant associations between at-risk alcohol use and osteocalcin, and at-risk alcohol use and serum 4-HNE, suggesting suppression of bone formation independent of increased systemic oxidative stress with increasing alcohol consumption.

The New Orleans Alcohol Use in HIV Study: Launching a Translational Investigation of the Interaction of Alcohol Use with Biological and Socioenvironmental Risk Factors for Multimorbidity in People Living with HIV.

BACKGROUND: Alcohol use disorders (AUDs) are highly prevalent in people living with HIV (PLWH) and are associated with increased HIV risk behaviors, suboptimal treatment adherence, potential interaction with medication pharmacodynamics, and greater risk for disease progression. Preclinical studies show that chronic binge alcohol administration accelerates disease progression and aggravates pathogenesis in the simian immunodeficiency virus (SIV)-infected rhesus macaque model despite viral suppression by antiretroviral therapy. METHODS: To translate preclinical findings in the rhesus macaque model of chronic binge alcohol administration and SIV infection and to address areas of uncertainty surrounding the biological mechanisms and socioenvironmental modifiers that contribute to the relationship between alcohol use and HIV-associated comorbidities, precocious aging, and disease progression, we designed a translational multiproject, longitudinal, cohort study, and the New Orleans Alcohol Use in HIV (NOAH) Study. The NOAH Study is led by a multidisciplinary team of scientists, with a research focus on the interaction of AUD and HIV. The overarching hypothesis is that alcohol use will lead to adverse health outcomes in PLWH. In this report, we describe the study design and baseline descriptive characteristics of our cohort. RESULTS: Three-hundred and sixty-five participants completed the baseline testing. The cohort is predominantly male (69%) and African American (83.5%). The majority of participants report incomes below 200% of the federal poverty level. CD4 counts <200 cells/µl were found in 12.8% and viral loads <50 copies/ml were found in 73.6%. These HIV status variables did not differ based upon alcohol use. CONCLUSIONS: The NOAH Study facilitates bidirectional translational investigation of alcohol's impact on PLWH. Translation of preclinical findings to PLWH permits confirmation of basic biological mechanisms in humans and also allows incorporation of sociobehavioral factors that may affect biology but are challenging to replicate in preclinical models.

Latent Alcohol Use Typologies and Health Status Among a Cohort of Adults Living with HIV.

AIMS: To characterize latent typologies of alcohol use among persons living with human immunodeficiency virus (HIV) (PLWH) and test their relationship with physical and mental health status. METHODS: Baseline data from 365 adult in-care PLWH enrolled in the New Orleans Alcohol Use in HIV study were analyzed. Indicators of current and former heavy drinking, intoxication, withdrawal and dependence symptoms, alcohol-related problems and past contact with alcohol use treatment were drawn from validated scales. Physical and mental health measures included SF-36 subscales, medication non-adherence and anxiety, depressive and post-traumatic stress disorder symptoms. Latent class analysis was conducted to characterize alcohol drinking typologies. Logistic and ordinary least-squares regression were employed to test associations between alcohol use and health status. RESULTS: Four latent classes were identified: heavy drinkers (36%), former heavy drinkers (14%), heavy drinkers with problems (12%) and low-risk drinkers/abstainers (38%). Controlling for background characteristics, low-risk drinkers/abstainers showed significantly better health compared to heavy drinkers with problems across most domains. Although current and former heavy drinkers without alcohol-related problems were similar to heavy drinkers with problems in most health domains, they presented worse mental health and energy compared to low-risk drinkers/abstainers. CONCLUSIONS: Heavy drinkers with alcohol-related problems evidenced the worst health status among PLWH, and should be considered for mental and physical health interventions. However, interventions to improve physical and mental health of PLWH should consider history of heavy alcohol use, as current alcohol use status alone may be insufficient for identifying groups at increased risk.

Chronic Binge Alcohol-Associated Differential Brain Region Modulation of Growth Factor Signaling Pathways and Neuroinflammation in Simian Immunodeficiency Virus-Infected Male Macaques.

AIMS: Microarray analysis of hippocampal tissue from chronic binge alcohol (CBA)-administered, simian immunodeficiency virus (SIV)-infected male macaques identified altered immune response and neurogenesis as potential mechanisms underlying cognitive deficits in macaques. This study investigated the differential brain region associations between markers of neuroinflammation and growth factor signaling with microtubule-associated protein 2 (MAP2) expression. METHODS: Adult male rhesus macaques were administered CBA (13-14 g EtOH/kg/week, n = 8) or sucrose (SUC, n = 7) beginning 3 months prior to SIV infection and continued until animals reached end-stage disease criteria (3-24 months post infection). Expression of inflammatory cytokines, growth factors, and viral loads were determined in the prefrontal cortex (PFC), caudate (CD), and hippocampus (HP). Brain-derived neurotropic factor (BDNF) expression and phosphorylation of intracellular kinases downstream of BDNF were investigated in the PFC. RESULTS: Our results show reduced MAP2 expression in the PFC of longer-surviving, CBA/SIV macaques. BDNF expression was most closely associated with MAP2 expression in the PFC. In the caudate, significant positive associations were observed between MAP2 and BDNF, time to end-stage and set-point viral load and significant negative associations for CBA. In the hippocampus, positive associations were observed between MAP2 and inflammatory cytokines, and negative associations for brain viral load and CBA. CONCLUSIONS: CBA differentially affects growth factor and inflammatory cytokine expression and viral load across brain regions. In the PFC, suppression of growth factor signaling may be an important neuropathological mechanism, while inflammatory processes may play a more important role in the CD and HP.

Impact of chemotherapy relative dose intensity on cause-specific and overall survival for stage I-III breast cancer: ER+/PR+, HER2- vs. triple-negative.

PURPOSE: To investigate the impact of chemotherapy relative dose intensity (RDI) on cause-specific and overall survival for stage I-III breast cancer: estrogen receptor or progesterone receptor positive, human epidermal-growth factor receptor negative (ER+/PR+ and HER2-) vs. triple-negative (TNBC) and to identify the optimal RDI cut-off points in these two patient populations. METHODS: Data were collected by the Louisiana Tumor Registry for two CDC-funded projects. Women diagnosed with stage I-III ER+/PR+, HER2- breast cancer, or TNBC in 2011 with complete information on RDI were included. Five RDI cut-off points (95, 90, 85, 80, and 75%) were evaluated on cause-specific and overall survival, adjusting for multiple demographic variables, tumor characteristics, comorbidity, use of granulocyte-growth factor/cytokines, chemotherapy delay, chemotherapy regimens, and use of hormone therapy. Cox proportional hazards models and Kaplan-Meier survival curves were estimated and adjusted by stabilized inverse probability treatment weighting (IPTW) of propensity score. RESULTS: Of 494 ER+/PR+, HER2- patients and 180 TNBC patients, RDI < 85% accounted for 30.4 and 27.8%, respectively. Among ER+/PR+, HER2- patients, 85% was the only cut-off point at which the low RDI was significantly associated with worse overall survival (HR = 1.93; 95% CI 1.09-3.40). Among TNBC patients, 75% was the cut-off point at which the high RDI was associated with better cause-specific (HR = 2.64; 95% CI 1.09, 6.38) and overall survival (HR = 2.39; 95% CI 1.04-5.51). CONCLUSIONS: Higher RDI of chemotherapy is associated with better survival for ER+/PR+, HER2- patients and TNBC patients. To optimize survival benefits, RDI should be maintained ≥ 85% in ER+/PR+, HER2- patients, and ≥ 75% in TNBC patients.

Impact of Alcohol on HIV Disease Pathogenesis, Comorbidities and Aging: Integrating Preclinical and Clinical Findings.

SHORT SUMMARY: : Effective combined antiretroviral therapy regimens have extended survival of persons living with HIV (PLWH). Heavy alcohol consumption is common in PLWH. This overview integrates evidence from clinical and preclinical research to identify salient alcohol-related mechanisms and comorbidities contributing to disease pathogenesis and accelerated aging and senescence in PLWH.

Differences in Treating Tobacco Use Across National, State, and Public Hospital System Surveys.

The Louisiana Tobacco Control Initiative (TCI), a multidisciplinary program specializing in helping tobacco users quit, assisted health care providers in Louisiana's public hospitals with integrating evidence-based treatment of tobacco use into clinical practice. Our study compared smoking behavior, provider adherence to the 5 A's tobacco cessation intervention (ask, advise, assess, assist, and arrange), cessation assistance awareness, quit attempts, and treatment preference among respondents to a TCI survey with a sample of respondents from the National Adult Tobacco Survey (NATS) and a sample from the Louisiana Adult Tobacco Survey (LATS). In 2010, more TCI respondents were asked if they smoked, advised to quit, helped to set a quit date, counseled, and arranged to be contacted for follow-up than respondents to NATS or LATS. Fewer TCI respondents received self-help material or were prescribed medication to assist in quitting than NATS and LATS respondents. In 2010 and 2013, TCI participants reported more quit attempts when 4 or more of the 5 A's were received. Thus, public health systems can promote treatment of tobacco use.