Does smoking cessation reduce other substance use, psychiatric symptoms, and pain symptoms? Results from an emulated hypothetical randomized trial of US veterans.

BACKGROUND: Quitting smoking may lead to improvement in substance use, psychiatric symptoms, and pain, especially among high-risk populations who are more likely to experience comorbid conditions. However, causal inferences regarding smoking cessation and its subsequent benefits have been limited. METHODS: We emulated a hypothetical open-label randomized control trial of smoking cessation using longitudinal observational data of HIV-positive and HIV-negative US veterans from 2003-2015 in the Veterans Aging Cohort Study. We followed individuals from the first time they self-reported current cigarette smoking (baseline). We categorized participants as quitters or non-quitters at the first follow-up visit (approximately 1 year after baseline). Using inverse probability weighting to adjust for confounding and selection bias, we estimated odds ratios for improvement of co-occurring conditions (unhealthy alcohol use, cannabis use, illicit opioid use, cocaine use, depressive symptoms, anxiety symptoms, and pain symptoms) at second follow-up (approximately 2 years after baseline) for those who quit smoking compared to those who did not, among individuals who had the condition at baseline. RESULTS: Of 4,165 eligible individuals (i.e., current smokers at baseline), 419 reported no current smoking and 2,330 reported current smoking at the first follow-up. Adjusted odds ratios (95% confidence intervals) for associations between quitting smoking and improvement of each condition at second follow-up were: 2.10 (1.01, 4.35) for unhealthy alcohol use, 1.75 (1.00, 3.06) for cannabis use, 1.10 (0.58, 2.08) for illicit opioid use, and 2.25 (1.20, 4.24) for cocaine use, 0.78 (0.44, 1.38) for depressive symptoms, 0.93 (0.58, 1.49) for anxiety symptoms, and 1.31 (0.84, 2.06) for pain symptoms. CONCLUSIONS: While a causal interpretation of our findings may not be warranted, we found evidence for decreased substance use among veterans who quit cigarette smoking but none for the resolution of psychiatric conditions or pain symptoms. Findings suggest the need for additional resources combined with smoking cessation to reduce psychiatric and pain symptoms for high-risk populations.

Experimentally Induced Reductions in Alcohol Consumption and Brain, Cognitive, and Clinical Outcomes in Older Persons With and Those Without HIV Infection (30-Day Challenge Study): Protocol for a Nonrandomized Clinical Trial.

BACKGROUND: Both alcohol consumption and HIV infection are associated with worse brain, cognitive, and clinical outcomes in older adults. However, the extent to which brain and cognitive dysfunction is reversible with reduction or cessation of drinking is unknown. OBJECTIVE: The 30-Day Challenge study was designed to determine whether reduction or cessation of drinking would be associated with improvements in cognition, reduction of systemic and brain inflammation, and improvement in HIV-related outcomes in adults with heavy drinking. METHODS: The study design was a mechanistic experimental trial, in which all participants received an alcohol reduction intervention followed by repeated assessments of behavioral and clinical outcomes. Persons were eligible if they were 45 years of age or older, had weekly alcohol consumption of 21 or more drinks (men) or 14 or more drinks (women), and were not at high risk of alcohol withdrawal. After a baseline assessment, participants received an intervention consisting of contingency management (money for nondrinking days) for at least 30 days followed by a brief motivational interview. After this, participants could either resume drinking or not. Study questionnaires, neurocognitive assessments, neuroimaging, and blood, urine, and stool samples were collected at baseline, 30 days, 90 days, and 1 year after enrollment. RESULTS: We enrolled 57 persons with heavy drinking who initiated the contingency management protocol (mean age 56 years, SD 4.6 years; 63%, n=36 male, 77%, n=44 Black, and 58%, n=33 people with HIV) of whom 50 completed 30-day follow-up and 43 the 90-day follow-up. The planned study procedures were interrupted and modified due to the COVID-19 pandemic of 2020-2021. CONCLUSIONS: This was the first study seeking to assess changes in brain (neuroimaging) and cognition after alcohol intervention in nontreatment-seeking people with HIV together with people without HIV as controls. Study design strengths, limitations, and lessons for future study design considerations are discussed. Planned analyses are in progress, after which deidentified study data will be available for sharing. TRIAL REGISTRATION: ClinicalTrials.gov NCT03353701; https://clinicaltrials.gov/study/NCT03353701. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53684.

Alcohol Consumption and Illicit Drug Use: Associations With Fall, Fracture, and Acute Health Care Utilization Among People With HIV Infection.

BACKGROUND: Given alcohol and/or other drug (AOD) use occurs among people with HIV (PWH), we examined its association with falls and fall-related outcomes and whether frailty moderates the association. SETTING: Northeastern US city. METHODS: We analyzed an observational cohort of PWH with current or past AOD use. Alcohol measures were any past 14-day heavy use, average alcohol/day, and days with heavy use. Drug use measures were past 30-day illicit use of cocaine, opioids, and sedatives. Repeated cross-sectional associations were estimated with separate multivariable generalized estimating equation regression models for each fall-related outcome. RESULTS: Among PWH (n = 251; mean age 52 [SD = 10]), 35% reported heavy alcohol use, 24% cocaine, 16% illicit opioids, 13% illicit sedatives, and 35% any fall; 27% were frail. Heavy alcohol use was associated with a fall (AOR = 1.49, 95% CI: 1.08 to 2.07), multiple falls (AOR = 1.55 95% CI: 1.10 to 2.19), and fall/fracture-related emergency department visit or hospitalization (AOR = 1.81, 95% CI: 1.10 to 2.97). Higher average alcohol/day and more heavy drinking days were associated with multiple falls. Illicit sedative use was associated with a fall, multiple falls, and emergency department visit/hospitalization and opioid use with fracture. Frailty moderated the association of heavy alcohol use and a fall (AOR = 2.26, 95% CI: 1.28 to 4.01 in those frail) but not in those not frail. CONCLUSION: The effect of AOD use on falls and fall-related outcomes was most pronounced with alcohol, particularly among frail PWH. Heavy alcohol, illicit sedative, and illicit opioid use are high-priority targets for preventing falls and fall-related consequences for PWH.

Contingency management with stepped care for unhealthy alcohol use among individuals with HIV: Protocol for a randomized controlled trial.

BACKGROUND: Although unhealthy alcohol use is associated with increased morbidity and mortality among people with HIV (PWH), many are ambivalent about engaging in treatment and experience variable responses to treatment. We describe the rationale, aims, and study design for the Financial Incentives, Randomization, with Stepped Treatment (FIRST) Trial, a multi-site randomized controlled efficacy trial. METHODS: PWH in care recruited from clinics across the United States who reported unhealthy alcohol use, had a phosphatidylethanol (PEth) >20 ng/mL, and were not engaged in formal alcohol treatment were randomized to integrated contingency management with stepped care versus treatment as usual. The intervention involved two steps; Step 1: Contingency management (n = 5 sessions) with potential rewards based on 1) short-term abstinence; 2) longer-term abstinence; and 3) completion of healthy activities to promote progress in addressing alcohol consumption or conditions potentially impacted by alcohol; Step 2: Addiction physician management (n = 6 sessions) plus motivational enhancement therapy (n = 4 sessions). Participants' treatment was stepped up at week 12 if they lacked evidence of longer-term abstinence. Primary outcome was abstinence at week 24. Secondary outcomes included alcohol consumption (assessed by TLFB and PEth) and the Veterans Aging Cohort Study (VACS) Index 2.0 scores; exploratory outcomes included progress in addressing medical conditions potentially impacted by alcohol. Protocol adaptations due to the COVID-19 pandemic are described. CONCLUSIONS: The FIRST Trial is anticipated to yield insights on the feasibility and preliminary efficacy of integrated contingency management with stepped care to address unhealthy alcohol use among PWH. CLINICALTRIALS: gov identifier: NCT03089320.

Potential health benefits of integrated screening strategies for alcohol, tobacco, other substance use, depression, anxiety, and chronic pain among people living with HIV in the USA: a mathematical modelling study.

BACKGROUND: Alcohol use, tobacco use, and other substance use often co-occur with depression, anxiety, and chronic pain, forming a constellation of alcohol, substance, and mood-related (CASM) conditions that disproportionately affects people with HIV in the USA. We used a microsimulation model to evaluate how alternative screening strategies accounting for CASM interdependence could affect life expectancy in people with HIV in the USA. METHODS: We augmented a microsimulation model previously validated to predict US adult life expectancy, including in people with HIV. Using data from the Veterans Aging Cohort Study, we incorporated CASM co-occurrence, inferred causal relationships between CASM conditions, and assessed the effects of CASM on HIV treatment and preventive care. We simulated an in-care HIV cohort exposed to alternative CASM screening and diagnostic assessment strategies, ranging from currently recommended screenings (alcohol, tobacco, and depression, with diagnostic assessments for conditions screening positive) to a series of integrated strategies (screening for alcohol, tobacco, or depression with additional diagnostic assessments if any screened positive) to a maximal saturation strategy (diagnostic assessments for all CASM conditions). FINDINGS: The saturation strategy increased life expectancy by 0·95 years (95% CI 0·93-0·98) compared with no screening. Recommended screenings provided much less benefit: 0·06 years (0·03-0·09) gained from alcohol screening, 0·08 years (0·06-0·11) from tobacco screening, 0·10 years (0·08-0·11) from depression screening, and 0·25 years (0·22-0·27) from all three screenings together. One integrated strategy (screening alcohol, tobacco, and depression with diagnostic assessment for all CASM conditions if any screened positive) produced near-maximal benefit (0·82 years [0·80-0·84]) without adding substantial screening burden, albeit requiring additional diagnostic assessments. INTERPRETATION: Primary care providers for people with HIV should consider comprehensive diagnostic assessment of CASM conditions if one or more conditions screen positive. FUNDING: US National Institute on Alcohol Abuse and Alcoholism.

Characterizing Unhealthy Alcohol Use Patterns and Their Association with Alcohol Use Reduction and Alcohol Use Disorder During Follow-Up in HIV Care.

Outcomes of PWH with unhealthy alcohol use, such as alcohol use reduction or progression to AUD, are not well-known and may differ by baseline patterns of unhealthy alcohol use. Among 1299 PWH screening positive for NIAAA-defined unhealthy alcohol use in Kaiser Permanente Northern California, 2013-2017, we compared 2-year probabilities of reduction to low-risk/no alcohol use and rates of new AUD diagnoses by baseline use patterns, categorized as exceeding: only daily limits (72% of included PWH), only weekly limits (17%), or both (11%), based on NIAAA recommendations. Overall, 73.2% (95% CI 70.5-75.9%) of re-screened PWH reduced to low-risk/no alcohol use over 2 years, and there were 3.1 (95% CI 2.5-3.8%) new AUD diagnoses per 100 person-years. Compared with PWH only exceeding daily limits at baseline, those only exceeding weekly limits and those exceeding both limits were less likely to reduce and likelier to be diagnosed with AUD during follow-up. PWH exceeding weekly drinking limits, with or without exceeding daily limits, may have a potential need for targeted interventions to address unhealthy alcohol use.

Combining Charlson comorbidity and VACS indices improves prognostic accuracy for all-cause mortality for patients with and without HIV in the Veterans Health Administration.

Introduction: As people age with HIV (PWH), many comorbid diseases are more common than among age matched comparators without HIV (PWoH). While the Veterans Aging Cohort (VACS) Index 2.0 accurately predicts mortality in PWH using age and clinical biomarkers, the only included comorbidity is hepatitis C. We asked whether adding comorbid disease groupings from the Charlson Comorbidity Index (CCI) improves the accuracy of VACS Index. Methods: To maximize our ability to model mortality among older age groups, we began with PWoH in Veterans Health Administration (VA) from 2007-2017, divided into development and validation samples. Baseline predictors included age, and components of CCI and VACS Index (excluding CD4 count and HIV RNA). Patients were followed until December 31, 2021. We used Cox models to develop the VACS-CCI score and estimated mortality using a parametric (gamma) survival model. We compared accuracy using C-statistics and calibration curves in validation overall and within subgroups (gender, age

Patient-Reported Bothersome Symptoms Attributed to Alcohol Use Among People With and Without HIV.

Helping people with HIV (PWH) and without HIV (PWoH) understand the relationship between physical symptoms and alcohol use might help motivate them to decrease use. In surveys collected in the Veterans Aging Cohort Study from 2002 to 2018, PWH and PWoH were asked about 20 common symptoms and whether they thought any were caused by alcohol use. Analyses were restricted to current alcohol users (AUDIT-C > 0). We applied generalized estimating equations. The outcome was having any Symptoms Attributed to Alcohol use (SxAA). Primary independent variables were each of the 20 symptoms and HIV status. Compared to PWoH, PWH had increased odds of SxAA (OR 1.54; 95% CI 1.27, 1.88). Increased AUDIT-C score was also associated with SxAA (OR 1.32; 95% CI 1.28, 1.36), as were trouble remembering, anxiety, and weight loss/wasting. Evidence that specific symptoms are attributed to alcohol use may help motive people with and without HIV decrease their alcohol use.

Change in Alcohol Use Based on Self-Report and a Quantitative Biomarker, Phosphatidylethanol, in People With HIV.

The timeline followback (TLFB) takes more resources to collect than the Alcohol Use Disorder Identification Test (AUDIT-C). We assessed agreement of TLFB and AUDIT-C with the biomarker phosphatidylethanol (PEth) and compared changes in TLFB and PEth among persons with HIV (PWH) using secondary data from randomized trials. We calculated operating characteristics and agreement between TLFB (> 1 and > 2 average drinks/day), AUDIT-C ≥ 4 and PEth ≥ 20 among 275 men with HIV. Median age was 57 years, 80% were African-American; and 17% white. Sixty-eight percent had PEth ≥ 20, 46% reported > 2 average drinks/day on TLFB, 61% reported > 1 average drinks/day on TLFB, and 72% had an AUDIT-C ≥ 4. Relative to PEth, sensitivity for AUDIT-C ≥ 4 was 84% (kappa = 0.36), and for TLFB > 1 average drink/day was 76% (kappa = 0.44). Change in alcohol use appeared greater using TLFB measures than PEth. Strategies to robustly assess alcohol use in PWH may require both self-report and biomarkers.

Treatment for alcohol use disorder among persons with and without HIV in a clinical care setting in the United States.

BACKGROUND: Alcohol use disorders (AUD) can lead to poor health outcomes. Little is known about AUD treatment among persons with HIV (PWH). In an integrated health system in Northern California, 2014-2017, we compared AUD treatment rates between PWH with AUD and persons without HIV (PWoH) with AUD. METHODS: Using Poisson regression with GEE, we estimated prevalence ratios (PRs) comparing the annual probability of receiving AUD treatment (behavioral intervention or dispensed medication), adjusted for sociodemographics, psychiatric comorbidities, insurance type, and calendar year. Among PWH, we examined independent AUD treatment predictors using PRs adjusted for calendar year only. RESULTS: PWH with AUD (N = 633; 93% men, median age 49) were likelier than PWoH with AUD (N = 7006; 95% men, median age 52) to have depression (38% vs. 21%) and a non-alcohol substance use disorder (SUD, 48% vs. 25%) (both P < 0.01). Annual probabilities of receiving AUD treatment were 45.4% for PWH and 34.4% for PWoH. After adjusting, there was no difference by HIV status (PR 1.02 [95% CI 0.94-1.11]; P = 0.61). Of treated PWH, 59% received only a behavioral intervention, 5% only a medication, and 36% both, vs. 67%, 4%, 30% for treated PWoH, respectively. Irrespective of HIV status, the most common medication was gabapentin. Among PWH, receiving AUD treatment was associated with having depression (PR 1.78 [1.51-2.10]; P < 0.01) and another SUD (PR 2.68 [2.20-3.27]; P < 0.01). CONCLUSIONS: PWH with AUD had higher AUD treatment rates than PWoH with AUD in unadjusted but not adjusted analyses, which may be explained by higher psychiatric comorbidity burden among PWH.

Association of Syndemic Unhealthy Alcohol Use, Smoking, and Depressive Symptoms on Incident Cardiovascular Disease among Veterans With and Without HIV-Infection.

Unhealthy alcohol use, smoking, and depressive symptoms are risk factors for cardiovascular disease (CVD). Little is known about their co-occurrence - termed a syndemic, defined as the synergistic effect of two or more conditions-on CVD risk in people with HIV (PWH). We used data from 5621 CVD-free participants (51% PWH) in the Veteran's Aging Cohort Study-8, a prospective, observational study of veterans followed from 2002 to 2014 to assess the association between this syndemic and incident CVD by HIV status. Diagnostic codes identified cases of CVD (acute myocardial infarction, stroke, heart failure, peripheral artery disease, and coronary revascularization). Validated measures of alcohol use, smoking, and depressive symptoms were used. Baseline number of syndemic conditions was categorized (0, 1, ≥ 2 conditions). Multivariable Cox Proportional Hazards regressions estimated risk of the syndemic (≥ 2 conditions) on incident CVD by HIV-status. There were 1149 cases of incident CVD (52% PWH) during the follow-up (median 10.1 years). Of the total sample, 64% met our syndemic definition. The syndemic was associated with greater risk for incident CVD among PWH (Hazard Ratio [HR] 1.87 [1.47-2.38], p < 0.001) and HIV-negative veterans (HR 1.70 [1.35-2.13], p < 0.001), compared to HIV-negative with zero conditions. Among those with the syndemic, CVD risk was not statistically significantly higher among PWH vs. HIV-negative (HR 1.10 [0.89, 1.37], p = .38). Given the high prevalence of this syndemic combined with excess risk of CVD, these findings support linked-screening and treatment efforts.

Reduced Working Memory is Associated with Heavier Alcohol Consumption History, Role Impairment and Executive Function Difficulties.

Both HIV status and heavy alcohol use have been associated with reduced cognitive function, particularly in the domains of working memory and executive function. It is unclear what aspects of working memory and executive function are associated with HIV status and heavy alcohol use and whether performance on these measures are associated with functional impairment. We examined the relationship between HIV, history of heavy alcohol consumption, and HIV/alcohol interaction on speeded tests of frontal inhibitory abilities, a working memory task related to mental manipulation of letters and numbers, cognitive flexibility, and measures of functional impairment. Study participants included 284 individuals (151 HIV +) recruited from two different studies focusing on HIV associated brain dysfunction, one specific to the effects of alcohol, the other specific to the effects of aging. HIV status was not independently associated with working memory and executive function measures. Higher level of alcohol consumption was associated with reduced performance on Letter Number Sequencing. Poorer Letter Number Sequencing performance was associated with role impairment (an inability to do certain kinds of work, housework, or schoolwork) and executive function difficulties. Future studies should examine causal associations and interventions targeting working memory abilities.

RESUMEN: Tanto el estado del VIH como el consumo excesivo de alcohol se han asociado con una función cognitiva reducida, particularmente en los dominios de la memoria de trabajo y la función ejecutiva. No está claro qué aspectos de la memoria de trabajo y la función ejecutiva están asociados con el estado del VIH y el consumo excesivo de alcohol y si el desempeño en estas medidas está asociado con un deterioro funcional. Examinamos la relación entre el VIH, el historial de consumo excesivo de alcohol y la interacción VIH / alcohol, en pruebas aceleradas de capacidades inhibitorias frontales, tareas de memoria de trabajo relacionadas con la manipulación mental de letras y números, flexibilidad cognitiva y medidas de deterioro funcional. Los participantes del estudio incluyeron 284 personas (151 VIH +) reclutadas de dos estudios diferentes que se centran en la disfunción cerebral asociada al VIH, uno específico de los efectos del alcohol y el otro específico de los efectos del envejecimiento. El estado del VIH no se asoció de forma independiente con las medidas de memoria de trabajo y función ejecutiva. Un mayor nivel de consumo de alcohol se asoció con un rendimiento reducido en la secuenciación de números de letras. Un desempeño deficiente en la secuenciación de números de letras se asoció con un deterioro de los roles (una incapacidad para realizar ciertos tipos de trabajo, tareas domésticas o escolares) y dificultades en las funciones ejecutivas. Los estudios futuros deben examinar las asociaciones causales y las intervenciones dirigidas a las capacidades de la memoria de trabajo.

The relationship of smoking and unhealthy alcohol use to the HIV care continuum among people with HIV in an integrated health care system.

INTRODUCTION: Smoking tobacco and unhealthy alcohol use may negatively influence HIV care continuum outcomes but have not been examined in combination. METHODS: Participants were people with HIV (PWH) in Kaiser Permanente Northern California. Predictors included smoking status and unhealthy alcohol use (exceeding daily and/or weekly limits) reported by patients during primary care screening (index date). Outcomes were based on not achieving the following steps in the care continuum: linkage to HIV care (≥1 visit within 90 days of newly identified HIV diagnosis), retention (2+ in-person visits, 60+ days apart) and HIV RNA control (<75 copies/mL). Adjusted odds ratios (ORs) were obtained from separate logistic regression models for each outcome associated with smoking and unhealthy alcohol use independently and combined. RESULTS: The overall sample (N = 8958) had a mean age of 48.0 years; was 91.3 % male; 54.0 % white, 17.6 % Latino, 15.1 % black, and 9.6 % other race/ethnicity. Smoking was associated with higher odds of not being linked to HIV care (OR = 1.60 [95 % CI 1.03-2.48]), not retained (OR = 1.30 [95 % CI 1.13-1.50]), and HIV RNA not in control (OR = 1.91 [95 % CI 1.60-2.27]). Alcohol measures were not independently associated with outcomes. The combination of unhealthy alcohol use and smoking (versus neither) was associated with higher odds of not being linked to care (OR = 2.83 [95 % CI 1.40-5.71]), although the interaction did not reach significance (p = 0.18). CONCLUSIONS: In this large sample of PWH in an integrated health care system, smoking, both independently and in combination with unhealthy alcohol use, was associated with worse HIV care continuum outcomes.

Alcohol Use and Antiretroviral Adherence Among Patients Living with HIV: Is Change in Alcohol Use Associated with Change in Adherence?

Alcohol use increases non-adherence to antiretroviral therapy (ART) among persons living with HIV (PLWH). Dynamic longitudinal associations are understudied. Veterans Aging Cohort Study (VACS) data 2/1/2008-7/31/16 were used to fit linear regression models estimating changes in adherence (% days with ART medication fill) associated with changes in alcohol use based on annual clinically-ascertained AUDIT-C screening scores (range - 12 to + 12, 0 = no change) adjusting for demographics and initial adherence. Among 21,275 PLWH (67,330 observations), most reported no (48%) or low-level (39%) alcohol use initially, with no (55%) or small (39% ≤ 3 points) annual change. Mean initial adherence was 86% (SD 21%), mean annual change was - 3.1% (SD 21%). An inverted V-shaped association was observed: both increases and decreases in AUDIT-C were associated with greater adherence decreases relative to stable scores [p < 0.001, F (4, 21,274)]. PLWH with dynamic alcohol use (potentially indicative of alcohol use disorder) should be considered for adherence interventions.

RESUMEN: El consumo de alcohol aumenta el no-cumplimiento a la terapia antirretroviral (TARV) entre las personas que viven con VIH. No se han estudiado lo suficiente las dinámicas asociaciones longitudinales. Los datos del Estudio de la Envejecimiento de Cohorte de Veteranos (EECV) (1/2/2008­31/7/2016) fueron usados para encajar modelos de regresión lineal estimando los cambios en cumplimiento (% de días con medicaciones TARV surtidas) asociados con los cambios en el consumo de alcohol basado en los resultados anuales de las evaluaciones AUDIT-C, determinadas clínicamente, (una gama de -12 a + 12, 0 = cero cambio) adaptándose a las estadísticas demográficas y cumplimiento inicial. Entre 21,275 personas que viven con VIH (67,330 observaciones), la mayoría reportó ningún (48%) o bajos niveles del (39%) consumo de alcohol inicialmente, con ningún (55%) o muy pequeño (39% ≤ 3 puntos) cambio anual. la media inicial de cumplimiento fue 86% (DE 21%). La media de cambio anual fue -3.1% (DE 21%). Se observó una asociación de forma V invertida: tanto los aumentos como las disminuciones en AUDIT-C fueron asociados con mayor disminuciones de cumplimiento en comparación con resultados estables (p < 0.001, F (4, 21,274)). Personas que viven con VIH con el consumo dinámico de alcohol (potencialmente indicativo de un trastorno por consumo de alcohol) deben ser considerados por intervenciones de cumplimiento.

Does Reducing Drinking in Patients with Unhealthy Alcohol Use Improve Pain Interference, Use of Other Substances, and Psychiatric Symptoms?

BACKGROUND: We aimed to investigate the impact of reducing drinking in patients with unhealthy alcohol use on improvement of chronic pain interference, substance use, and psychiatric symptoms. METHODS: We analyzed longitudinal data from 2003 to 2015 in the Veterans Aging Cohort Study, a prospective, multisite observational study of US veterans, by emulating a hypothetical randomized trial (a target trial). Alcohol use was assessed using the Alcohol Use Disorders Identification Test (AUDIT) questionnaire, and outcome conditions were assessed via validated survey items. Individuals were followed from the first time their AUDIT score was ≥ 8 (baseline), a threshold consistent with unhealthy alcohol use. We compared individuals who reduced drinking (AUDIT < 8) at the next follow-up visit with individuals who did not (AUDIT ≥ 8). We fit separate logistic regression models to estimate odds ratios for improvement of each condition 2 years postbaseline among individuals who had that condition at baseline: moderate or severe pain interference symptoms, tobacco smoking, cannabis use, cocaine use, depressive symptoms, and anxiety symptoms. Inverse probability weighting was used to account for potential selection bias and confounding. RESULTS: Adjusted 2-year odds ratios (95% confidence intervals) for associations between reducing drinking and improvement or resolution of each condition were as follows: 1.49 (0.91, 2.42) for pain interference symptoms, 1.57 (0.93, 2.63) for tobacco smoking, 1.65 (0.92, 2.95) for cannabis use, 1.83 (1.03, 3.27) for cocaine use, 1.11 (0.64, 1.92) for depressive symptoms, and 1.33 (0.80, 2.22) for anxiety symptoms. CONCLUSIONS: We found some evidence for improvement of pain interference symptoms and substance use after reducing drinking among US veterans with unhealthy alcohol use, but confidence intervals were wide.

Health System-Based Unhealthy Alcohol Use Screening and Treatment Comparing Demographically Matched Participants With and Without HIV.

BACKGROUND: Unhealthy alcohol use among persons living with HIV (PLWH) is linked to significant morbidity, and use of alcohol services may differ by HIV status. Our objective was to compare unhealthy alcohol use screening and treatment by HIV status in primary care. METHODS: Cohort study of adult (≥18 years) PLWH and HIV-uninfected participants frequency matched 20:1 to PLWH by age, sex, and race/ethnicity who were enrolled in a large integrated healthcare system in the United States, with information ascertained from an electronic health record. Outcomes included unhealthy alcohol screening, prevalence, provider-delivered brief interventions, and addiction specialty care visits. Other predictors included age, sex, race/ethnicity, neighborhood deprivation index, depression, smoking, substance use disorders, Charlson comorbidity index, prior outpatient visits, insurance type, and medical facility. Cox proportional hazards models were used to compute hazard ratios (HR) for the outcomes of time to unhealthy alcohol use screening and time to first addiction specialty visit. Poisson regression with robust standard errors was used to compute prevalence ratios (PR) for other outcomes. RESULTS: 11,235 PLWH and 227,320 HIV-uninfected participants were included. By 4.5 years after baseline, most participants were screened for unhealthy alcohol use (85% of PLWH and 93% of HIV-uninfected), but with a lower rate among PLWH (adjusted HR 0.84, 95% CI 0.82 to 0.85). PLWH were less likely, compared with HIV-uninfected participants, to report unhealthy drinking among those screened (adjusted PR 0.74, 95% CI 0.69 to 0.79), and among those who screened positive, less likely to receive brief interventions (adjusted PR 0.82, 95% CI 0.75 to 0.90), but more likely (adjusted HR 1.7, 95% CI 1.2 to 2.4) to have an addiction specialty visit within 1 year. CONCLUSIONS: Unhealthy alcohol use was lower in PLWH, but the treatment approach by HIV status differed. PLWH reporting unhealthy alcohol use received less brief interventions and more addiction specialty care than HIV-uninfected participants.

Integrated stepped alcohol treatment for patients with HIV and at-risk alcohol use: a randomized trial.

BACKGROUND: At-risk levels of alcohol use threaten the health of patients with HIV (PWH), yet evidence-based strategies to decrease alcohol use and improve HIV-related outcomes in this population are lacking. We examined the effectiveness of integrated stepped alcohol treatment (ISAT) on alcohol use and HIV outcomes among PWH and at-risk alcohol use. METHODS: In this multi-site, randomized trial conducted between January 28, 2013 through July 14, 2017, we enrolled PWH and at-risk alcohol use [defined as alcohol consumption of ≥ 14 drinks per week or ≥ 4 drinks per occasion in men ≤ 65 years old or ≥ 7 drinks per week or ≥ 3 drinks per occasion in women or men > 65 years old]. ISAT (n = 46) involved: Step 1- Brief Negotiated Interview with telephone booster, Step 2- Motivational Enhancement Therapy, and Step 3- Addiction Physician Management. Treatment as usual (TAU) (n = 47) involved receipt of a health handout plus routine care. Analyses were conducted based on intention to treat principles. RESULTS: Despite a multi-pronged approach, we only recruited 37% of the target population (n = 93/254). Among ISAT participants, 50% advanced to Step 2, among whom 57% advanced to Step 3. Participants randomized to ISAT and TAU had no observed difference in drinks per week over the past 30 days at week 24 (primary outcome) [least square means (Ls mean) (95% CI) = 8.8 vs. 10.6; adjusted mean difference (AMD) (95% CI) = - 0.4 (- 3.9, 3.0)]. CONCLUSION: An insufficient number of patients were interested in participating in the trial. Efforts to enhance motivation of PWH with at-risk alcohol use to engage in alcohol-related research and build upon ISAT are needed. Trial registration Clinicaltrials.gov: NCT01410123, First posted August 4, 2011.

Safety of Gabapentin Prescribed for Any Indication in a Large Clinical Cohort of 571,718 US Veterans with and without Alcohol Use Disorder.

BACKGROUND: Gabapentin is prescribed for seizures and pain and has efficacy for treating alcohol use disorder (AUD) starting at doses of 900 milligrams per day (mg/d). Recent evidence suggests safety concerns associated with gabapentin including adverse neurologic effects. Individuals with hepatitis C (HCV), HIV, or AUD may be at increased risk due to comorbidities and potential medication interactions. METHODS: We identified patients prescribed gabapentin for ≥ 60 days for any indication between 2002 and 2015. We propensity-score matched each gabapentin-exposed patient with up to 5 gabapentin-unexposed patients. We followed patients for 2 years or until diagnosed with (i) falls or fractures, or (ii) altered mental status using validated ICD-9 diagnostic codes. We used Poisson regression to estimate incidence rates and relative risk (RR) of these adverse events in association with gabapentin exposure overall and stratified by age, race/ethnicity, sex, HCV, HIV, AUD, and dose. RESULTS: Incidence of falls or fractures was 1.81 per 100 person-years (PY) among 140,310 gabapentin-exposed and 1.34/100 PY among 431,408 gabapentin-unexposed patients (RR 1.35, 95% confidence interval [CI] 1.28 to 1.44). Incidence of altered mental status was 1.08/100 PY among exposed and 0.97/100 PY among unexposed patients, RR of 1.12 (95% CI 1.04 to 1.20). Excess risk of falls or fractures associated with gabapentin exposure was observed in all subgroups except patients with HCV, HIV, or AUD; however, these groups had elevated incidence regardless of exposure. There was a clear dose-response relationship for falls or fractures with highest risk observed among those prescribed ≥ 2,400 mg/d (RR 1.90, 95% CI 1.50 to 2.40). Patients were at increased risk for altered mental status at doses 600 to 2,399 mg/d; however, low number of events in the highest dose category limited power to detect a statistically significant association ≥ 2,400 mg/d. CONCLUSIONS: Gabapentin is associated with falls or fractures and altered mental status. Clinicians should be monitoring gabapentin safety, especially at doses ≥ 600 mg/d, in patients with and without AUD.

Association of Alcohol Screening Scores With Adverse Mental Health Conditions and Substance Use Among US Adults.

Importance: Alcohol screening may be associated with health outcomes that cluster with alcohol use (ie, alcohol-clustering conditions), including depression, anxiety, and use of tobacco, marijuana, and illicit drugs. Objective: To quantify the extent to which alcohol screening provides additional information regarding alcohol-clustering conditions and to compare 2 alcohol use screening tools commonly used for this purpose. Design, Setting, and Participants: This longitudinal cohort study used data from the Veterans Aging Cohort Study. Data were collected at 8 Veterans Health Administration facilities from 2003 through 2012. A total of 7510 participants were enrolled, completed a baseline survey, and were followed up. Veterans with HIV were matched with controls without HIV by age, race, sex, and site of care. Data were analyzed from January 2019 to December 2019. Exposures: The Alcohol Use Disorders Identification Test (AUDIT) and Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) were used to assess alcohol use, with 4 risk groups delineated for each test: score 0 to 7 (reference), score 8 to 15, score 16 to 19, and score 20 to 40 (maximum score) for the full AUDIT and score 0 to 3 (reference), score 4 to 5, score 6 to 7, and score 8 to 12 (maximum score) for the AUDIT-C. Main Outcomes and Measures: Alcohol-clustering conditions, including self-reported symptoms of depression and anxiety and use of tobacco, marijuana, cocaine, other stimulants, opioids, and injection drugs. Results: A total of 6431 US patients (6104 [95%] men; median age during survey years 2003-2004, 50 years [range, 28-86 years; interquartile range, 44-55 years]) receiving care in the Veterans Health Administration completed 1 or more follow-up surveys when the AUDIT was administered and were included in the present analyses. Of the male participants, 4271 (66%) were African American, 1498 (24%) were white, and 590 (9%) were Hispanic. The AUDIT and AUDIT-C scores were associated with each alcohol-clustering condition. In particular, an AUDIT score of 20 or higher (vs <8, the reference) was associated with symptoms of depression (odds ratio [OR], 8.37; 95% CI, 6.20-11.29) and anxiety (OR, 8.98; 95% CI, 6.39-12.60) and with self-reported use of tobacco (OR, 14.64; 95% CI, 8.94-23.98), marijuana (OR, 12.41; 95% CI, 8.61-17.90), crack or cocaine (OR, 39.47; 95% CI, 27.38-56.90), other stimulants (OR, 21.31; 95% CI, 12.73-35.67), and injection drugs (OR, 8.67; 95% CI, 5.32-14.13). An AUDIT score of 20 or higher yielded likelihood ratio (sensitivity / 1 - specificity) values greater than 3.5 for depression, anxiety, crack or cocaine use, and other stimulant use. Associations between AUDIT-C scores and alcohol-clustering conditions were more modest. Conclusions and Relevance: Alcohol screening can inform decisions about further screening and diagnostic assessment for alcohol-clustering conditions, particularly for depression, anxiety, crack or cocaine use, and other stimulant use. Future studies using clinical diagnoses rather than screening tools to assess alcohol-clustering conditions may be warranted.

Alcohol and Bone Turnover Markers among People Living with HIV and Substance Use Disorder.

BACKGROUND: Although unhealthy alcohol use and low bone density are prevalent among people living with HIV (PLWH), it is not clear whether alcohol use is associated with bone turnover markers (BTMs), and if so, at what quantity and frequency. The study objective was to examine the association between alcohol and BTMs in PLWH with substance use disorder. METHODS: We studied a prospective cohort recruited from 2 HIV clinics who met criteria for DSM-IV substance dependence or reported ever injection drug use. Outcomes were BTM of (i) bone formation (serum procollagen type 1 N-terminal propeptide [P1NP]) and (ii) bone resorption (serum C-telopeptide type 1 collagen [CTx]). Alcohol consumption measures included (i) mean number of drinks/d (Timeline Follow-Back [TLFB]) (primary predictor), (ii) any alcohol use on ≥20 of the past 30 days, and phosphatidylethanol (PEth), a biomarker of recent alcohol consumption. Linear regression analysis examined associations between (i) each alcohol measure and each BTM and (ii) change in alcohol and change in BTM over 12 months. RESULTS: Among 198 participants, baseline characteristics were as follows: The median age was 50 years; 38% were female; 93% were prescribed antiretroviral medications; 13% had ≥20 drinking days/month; mean drinks/day was 1.93 (SD 3.89); change in mean drinks/day was -0.42 (SD 4.18); mean P1NP was 73.1 ng/ml (SD 34.5); and mean CTx was 0.36 ng/ml (SD 0.34). Higher drinks/day was significantly associated with lower P1NP (slope -1.09 ng/ml; 95% confidence interval [CI] -1.94, -0.23, per each additional drink). On average, those who drank on ≥ 20 days/month had lower P1NP (-15.45 ng/ml; 95% CI: -26.23, -4.67) than those who did not. Similarly, PEth level ≥ 8ng/ml was associated with lower P1NP. An increase in drinks/d was associated with a decrease in P1NP nonsignificantly (-1.14; 95% CI: -2.40, +0.12; p = 0.08, per each additional drink). No significant associations were detected between either alcohol measure and CTx. CONCLUSIONS: In this sample of PLWH with substance use disorder, greater alcohol consumption was associated with lower serum levels of bone formation markers.