Immune activation and neuroinflammation in alcohol use and HIV infection: evidence for shared mechanisms

Background: Emerging research points to innate immune mechanisms in the neuropathological and behavioral consequences of heavy alcohol use. Alcohol use is common among people living with HIV infection (PLWH), a chronic condition that carries its own set of long-term effects on brain and behavior. Notably, neurobiological and cognitive profiles associated with heavy alcohol use and HIV infection share several prominent features. This observation raises questions about interacting biological mechanisms as well as compounded impairment when HIV infection and heavy drinking co-occur. Objective and Method: This narrative overview discusses peer-reviewed research on specific immune mechanisms of alcohol that exhibit apparent potential to compound the neurobiological and psychiatric sequelae of HIV infection. These include microbial translocation, systemic immune activation, blood-brain barrier compromise, microglial activation, and neuroinflammation. Results: Clinical and preclinical evidence supports overlapping mechanistic actions of HIV and alcohol use on peripheral and neural immune systems. In preclinical studies, innate immune signaling mediates many of the detrimental neurocognitive and behavioral effects of alcohol use. Neuropsychopharmacological research suggests potential for a feed-forward cycle in which heavy drinking induces innate immune signaling, which in turn stimulates subsequent alcohol use behavior. Conclusion: Alcohol-induced immune activation and neuroinflammation are a serious health concern for PLWH. Future research to investigate specific immune effects of alcohol in the context of HIV infection has potential to identify novel targets for therapeutic intervention.     

HIV Stigma and Unhealthy Alcohol Use Among People Living with HIV in Russia

Unhealthy alcohol use, highly prevalent in the Russian Federation (Russia), is associated with HIV risk behaviors among people living with HIV (PLWH). HIV stigma contributes to the HIV risk environment in Russia. To examine HIV stigma among Russian PLWH and to explore its association with unhealthy alcohol use, we conducted a longitudinal analysis of 700 PLWH in St. Petersburg, Russia. We assessed the association between alcohol dependence and HIV stigma measured at baseline and 12 months follow-up. Participants with alcohol dependence (n = 446) reported significantly higher HIV stigma scores over time than those without dependence (n = 254) (adjusted mean difference 0.60, 95% CI 0.03–1.17; p = 0.04). In secondary analyses, we examined recent risky alcohol use and did not detect an association with HIV stigma. Alcohol dependence is associated with high HIV stigma among Russian PLWH but the nature of the association is conjectural. HIV prevention efforts in Russia that address alcohol use disorders hold potential to mitigate HIV-related stigma and its possible adverse effects among PLWH.     

Alcohol and Opioid Use,Co‐Use,and Chronic Pain in the Context of the Opioid Epidemic: A Critical Review

The dramatic increase in opioid misuse, opioid use disorder (OUD), and opioid‐related overdose deaths in the United States has led to public outcry, policy statements, and funding initiatives. Meanwhile, alcohol misuse and alcohol use disorder (AUD) are a highly prevalent public health problem associated with considerable individual and societal costs. This study provides a critical review of alcohol and opioid misuse, including issues of prevalence, morbidity, and societal costs. We also review research on interactions between alcohol and opioid use, the influence of opioids and alcohol on AUD and OUD treatment outcomes, respectively, the role of pain in the co‐use of alcohol and opioids, and treatment of comorbid OUD and AUD. Heavy drinking, opioid misuse, and chronic pain individually represent significant public health problems. Few studies have examined co‐use of alcohol and opioids, but available data suggest that co‐use is common and likely contributes to opioid overdose‐related morbidity and mortality. Co‐use of opioids and alcohol is related to worse outcomes in treatment for either substance. Finally, chronic pain frequently co‐occurs with use (and co‐use) of alcohol and opioids. Opioid use and alcohol use are also likely to complicate the treatment of chronic pain. Research on the interactions between alcohol and opioids, as well as treatment of the comorbid disorders is lacking. Currently, most alcohol research excludes patients with OUD and there is lack of measurement in both AUD and OUD research in relation to pain‐related functioning. Research in those with chronic pain often assesses opioid use, but rarely assesses alcohol use or AUD. New research to examine the nexus of alcohol, opioids, and pain, as well as their treatment, is critically needed.     

Rapid initiation of antiretroviral therapy at HIV diagnosis: definition,process, knowledge gaps

Initiating antiretroviral therapy (ART) as early as the day of HIV diagnosis is a strategy of increasing global interest to control the HIV epidemic and optimize the health of people living with HIV (PLWH). No detrimental effects of rapid‐start ART have been identified in randomized controlled trials undertaken in low‐ or middle‐income countries, or in cohort studies performed in high‐income countries. Rapid‐start ART may be a key approach in reaching the 2020 Joint United Nations Programme on HIV/AIDS goal of 90% of all PLWH knowing their status, 90% of those diagnosed receiving sustained ART, and 90% of those receiving ART achieving viral suppression; it may also be important for achieving the suggested fourth “90%” goal: improving health‐related quality‐of‐life in PLWH. Presently there is insufficient broad evidence for guidelines to recommend universal test‐and‐treat strategies for all people, in all settings, at HIV diagnosis; consequently, there is a pressing need to conduct high‐quality studies that investigate immediate ART initiation. This article evaluates global evidence regarding rapid‐start ART, including same‐day start, with particular focus on the implementation of this strategy in high‐income countries.     

Pubertal development, sleep problems, and alcohol use: a commentary

Background: This commentary discussed the study conducted by Pieters et al. (2010 Alcohol Clin Exp Res in press) on the relationships among puberty dependent, sleep regulation, and alcohol use in adolescents. The goal of this commentary is to underscore the significance of the study and discuss some of the unaddressed questions in the area. Methods: The significance of the study and unaddressed questions are discussed. Results: Pieters et al. (2010 Alcohol Clin Exp Res in press) provided valuable data to understanding the relationships among puberty, sleep problems, and alcohol use. Questions regarding the relationship between puberty and sleep problems, the possible reciprocal relationships among circadian phase preference, sleep problems and alcohol use, mediators and moderators of such relationships, as well as potential gender differences on these relationships were discussed. Conclusions: To understand the relationships among pubertal development, sleep problems, and alcohol use, researchers need to be aware of the physiological changes that take place in puberty, as well as the psychosocial factors that are associated with such changes. Important mediators and moderators of the relationships among these constructs also need to be identified. Longitudinal design may be useful in this regard.     

Neuroimaging and Cognitive Evidence for Combined HIV-Alcohol Effects on the Central Nervous System: A Review

Alcohol use disorder (AUD) among people living with HIV (PLWH) is a significant public health concern. Despite the advent of effective antiretroviral therapy, up to 50% of PLWH still experience worsened neurocognition, which comorbid AUD exacerbates. We report converging lines of neuroimaging and neuropsychological evidence linking comorbid HIV/AUD to dysfunction in brain regions linked to executive function, learning and memory, processing speed, and motor control, and consequently to impairment in daily life. The brain shrinkage, functional network alterations, and brain metabolite disruption seen in individuals with HIV/AUD have been attributed to several interacting pathways: viral proteins and EtOH are directly neurotoxic and exacerbate each other’s neurotoxic effects; EtOH reduces antiretroviral adherence and increases viral replication; AUD and HIV both increase gut microbial translocation, promoting systemic inflammation and HIV transport into the brain by immune cells; and HIV may compound alcohol’s damaging effects on the liver, further increasing inflammation. We additionally review the neurocognitive effects of aging, Hepatitis C coinfection, obesity, and cardiovascular disease, tobacco use, and nutritional deficiencies, all of which have been shown to compound cognitive changes in HIV, AUD, and in their comorbidity. Finally, we examine emerging questions in HIV/AUD research, including genetic and cognitive protective factors, the role of binge drinking in HIV/AUD-linked cognitive decline, and whether neurocognitive and brain functions normalize after drinking cessation.     

Alcohol Use Disorders in ICD‐11: Past,Present, and Future

The Eleventh Revision of the International Classification of Diseases (ICD‐11) was formally published in May 2019. Alcohol use disorders form a key part of the section of Disorders due to Substance Use and Addictive Behaviours. This review describes and discusses the alcohol diagnoses within this section of ICD‐11, including Alcohol Dependence, Harmful Pattern of Use of Alcohol, and entities such as Alcohol Intoxication, Alcohol Withdrawal, and several alcohol‐induced mental disorders, and briefly covers Hazardous Alcohol Use, which is listed separately as a health risk factor. We summarize the historical background to the development of these diagnoses, including work within the World Health Organization since the 1970s, and the corresponding diagnoses in the current ICD‐10. The process by which ICD‐11 diagnoses have been made is described and may be summarized as a conceptual–pragmatic–confirmatory one. The available empirical data supporting the ICD‐11 diagnoses are presented, particularly in relation to the diagnostic guidelines for Alcohol Dependence. Comparison is made with the corresponding diagnoses in ICD‐10 and their nearest counterparts in the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders. Field testing of the ICD‐11 diagnoses is currently in progress. A plea is made for matching of diagnoses, diagnostic guidelines/criteria, and the assessment tools intended to capture these diagnoses.     

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.

     

Alcohol use disorders among emergency department-treated older adolescents: a new brief screen (RUFT-Cut) using the AUDIT, CAGE, CRAFFT, and RAPS-QF

BACKGROUND: Early identification of alcohol use disorders (AUD) among emergency department (ED)-treated patients is important for facilitating intervention and further evaluation outside EDs. A number of brief screening instruments have been developed for identifying patients with AUD, but it is not clear whether they are practical and perform well with older adolescents in an ED setting. This study contrasted four brief screening instruments for detecting DSM-IV-defined AUD and tested a newly developed brief screen for use among ED-treated older adolescents. METHODS: The Alcohol Use Disorders Identification Test (AUDIT), the CAGE, the CRAFFT, and a modified RAPS-QF were given to 93 alcohol-using older adolescents (55% men; aged 18-20 years) in an ED. Receiver operator characteristic analyses were used to evaluate the performance of brief screens against the criterion of a lifetime DSM-IV alcohol abuse or dependence diagnosis. RESULTS: Of existing instruments, the AUDIT had the best overall performance in identifying AUD (sensitivity, 82%; specificity, 78%). A new, shorter screening instrument composed of two AUDIT items, two CRAFFT items, and one CAGE item (RUFT-Cut) performed as well as the AUDIT (sensitivity, 82%; specificity, 78%). CONCLUSIONS: Among existing alcohol screening instruments, the AUDIT performed best for identifying ED-treated older adolescents with alcohol use disorders. The RUFT-Cut is a brief screening instrument for AUD that shows promise for identifying ED-treated older adolescents who are in need of intervention or further evaluation. Future research should focus on use of the RUFT-Cut in other settings with larger, more diverse samples of adolescents.     

The Veterans Aging Cohort Study: observational studies of alcohol use, abuse, and outcomes among human immunodeficiency virus-infected veterans

This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The organizers/chairs were Joseph Conigliaro and Amy Justice. The presentations were (1) Introduction, by Joseph Conigliaro and Tamra Madenwald; (2) Alcohol and HIV/AIDS: the importance of integrative and translational research, by Kendall Bryant; (3) Alcohol use and abuse among patients with HIV infection, by Joseph Conigliaro and Stephan Maisto; (4) Severity of comorbid alcohol use/abuse in HIV infection, by Amy Justice and Jeffrey Samet; (5) Estimating the impact of alcohol use on long-term HIV outcomes, by Scott Braithwaite and Amy Justice; (6) Homelessness, drug & alcohol use among HIV+ veterans, by Adam Gordon and Robert Cook; and (7) Hepatitis C & alcohol in the VACS 3 study, by Shawn Fultz and Kevin Kraemer. The symposium concluded with a discussion led and facilitated by Diedra Roach.     

Acceptance and Commitment Therapy (ACT) for HIV-infected Hazardous Drinkers: A Qualitative Study of Acceptability

Alcohol use is a significant problem in HIV care, and clinical trials of alcohol interventions for people living with HIV infection (PLWH) have produced mixed results. The purpose of this qualitative study was to collect preliminary data on the practical feasibility and acceptability of Acceptance and Commitment Therapy (ACT) as a treatment for PLWH who are hazardous drinkers. A total of 25 PLWH participated in individual interviews. Four major themes emerged from the thematic analysis: (1) perceived appropriateness for PLWH and people who use alcohol and/or other substances, (2) general satisfaction and dissatisfaction, (3) positive and negative effects on participants, and (4) facilitators and barriers to implementing act intervention strategies.     

Polydrug Use in Adolescent Drinkers with and without DSM-IV Alcohol Abuse and Dependence

Alcohol and other substance use disorders are highly comorbid, but little is known about patterns of polydrug use in adolescents with different levels of alcohol involvement. This research examined patterns and correlates of polydrug use in 176 adolescent drinkers with DSM-IV alcohol dependence ( n = 61), alcohol abuse ( n = 57), and no alcohol diagnosis ( n = 58). Alcohol and other Substance Use Disorders were assessed using a modified version of the Structured Clinical Interview for the DSM. Lifetime histories of alcohol use and other drug use were assessed using a structured interview. Subjects also completed a questionnaire measure of the frequency of use of specific alcohol-drug combinations. The total number of illicit drugs ever used was greater in the alcohol dependence (mean = 3.8, SD = 2.1) and abuse groups (mean = 3.0, SD = 2.1), compared with the no-alcohol diagnosis group (mean = 1.9, SD = 1.3). Consistent with previous findings, there was a consistent pattern in the age of onset of psychoactive substance use: alcohol, followed by marijuana, followed by other drugs. The recent use of alcohol and other drugs in combination was reported by a greater percentage of subjects in the alcohol dependence (69%) and abuse groups (72%), compared with drinkers without an alcohol diagnosis (45%). The most common alcohol-drug combination was alcohol with marijuana (58% of the total sample), followed by alcohol-hallucinogens (16%). The frequency and extent of polydrug use was associated with being older and having higher levels of behavioral undercontrol and negative emotionality. Adolescent polydrug use, particularly the use of alcohol and other drugs in combination, is an important area for research, treatment, and prevention.     

Dual dependence: assessment of dependence upon alcohol and illicit drugs, and the relationship of alcohol dependence among drug misusers to patterns of drinking, illicit drug use and health problems

Aims The study investigates severity of alcohol dependence among drug misusers. Specifically, it investigates the inter‐relationship of alcohol and drug dependence and associations with alcohol consumption, drug consumption and substance‐related problems. Design, setting, participants The sample comprised 735 people seeking treatment for drug misuse problems, who were current (last 90 days) drinkers. Measurements Data were collected by structured face‐to‐face interviews. Dependence upon illicit drugs and upon alcohol was measured by the Severity of Dependence Scale (SDS). Findings Three groups of drinkers were identified: non‐alcohol‐dependent drug misusers (63%); low‐dependence (19%); and high‐dependence (18%). Many drug misusers were drinking excessively and alcohol dependence was related to patterns of alcohol and drug consumption. High‐dependence drinkers were more likely to drink extra‐strength beer; they were less frequent users of heroin and crack cocaine but more frequent users of benzodiazepines, amphetamines and cocaine powder; they reported more psychological and physical health problems. The SDS was found to have good reliability and validity as a measure of alcohol dependence. SDS scores for alcohol and drug dependence were unrelated. Conclusions Alcohol use is an important and under‐rated problem in the treatment of drug misusers. A comprehensive assessment of alcohol use among drug misusers should include separate assessments of alcohol consumption, alcohol‐related problems and severity of alcohol dependence.     

Frequency,Quantity, and Contextual Use of Alcohol Among Sexually Transmitted Infection Clinic Patients in Cape Town,South Africa

Alcohol use is prevalent in South Africa and alcohol use may be associated with higher risk for HIV transmission. This article reports a study of the association between alcohol use and HIV risk-related behavior among 614 men and 157 women receiving sexually transmitted infection (STI) clinic services in Cape Town, South Africa. Participants completed anonymous surveys of demographic information, substance use, and sexual risk behaviors. Results for men showed that drinking in sexual contexts as well as their partner's drinking were related to higher rates of unprotected intercourse. However, the number of sex partners men reported was only associated with their own use of alcohol before sex. In contrast, women's partners drinking before sex was related to higher frequencies of unprotected intercourse, but it was their own drinking before sex that was related to women's number of sex partners. Results therefore suggest that the context of alcohol use is more closely related to sexual risks than are the quantity or frequency of use. Interventions are needed that integrate HIV risk reduction with alcohol risk reduction in South Africa.     

Polydrug Use in an Inpatient Treatment Sample of Problem Drinkers

Over the past 30 years in the United States, there have been marked secular increases in polydrug use. Alcohol and other substance use disorders are highly comorbid. Yet, little research has characterized patterns of polydrug use in persons with alcohol dependence. In particular, little is known about this population's use of alcohol and other drugs in combination or on the same day, which is termed simultaneous polydrug use (SPU). This research assessed patterns of SPU in 212 problem drinkers who participated in an alcohol treatment outcome study. Subjects were given a Time-Line Follow-Back interview that assessed the use of alcohol and nine other drug classes for each day of the 120 days before treatment entry. A majority of subjects (61%) reported SPU during this assessment interval. Subjects who reported SPU were disproportionately younger, male, and unmarried, compared with those who did not report SPU. The most common alcohol/drug combinations were alcohol with cocaine (60% of subjects who reported SPU), alcohol with marijuana (51 % of SPU subjects), and alcohol with sedatives (31 % of SPU subjects). The most common three-drug combination was alcohol, cocaine, and marijuana (23% of SPU subjects). Alcohol use and drug use were associated at the event level, significantly more than association predicted by the base rates of the individual behaviors. Time-Line Follow-Back data correlated highly with a questionnaire measure of SPU. Results indicate that polydrug use is an important focus for assessment and intervention in alcohol treatment programs.     

Is There a Recent Epidemic of Women's Drinking? A Critical Review of National Studies

Alcohol consumption is increasing in the United States, as is alcohol‐attributable mortality. Historically, men have had higher rates of alcohol consumption than women, though evidence for birth cohort effects on gender differences in alcohol consumption and alcohol‐related harm suggests that gender differences may be diminishing. We review studies using U.S. national data that examined time trends in alcohol consumption and alcohol‐related harm since 2008. Utilizing a historical–developmental perspective, here we synthesize and integrate the literature on birth cohort effects from varying developmental periods (i.e., adolescence, young adulthood, middle adulthood, and late adulthood), with a focus on gender differences in alcohol consumption. Findings suggest that recent trends in gender differences in alcohol outcomes are heterogeneous by developmental stage. Among adolescents and young adults, both males and females are rapidly decreasing alcohol consumption, binge and high‐intensity drinking, and alcohol‐related outcomes, with gender rates converging because males are decreasing consumption faster than females. This pattern does not hold among adults, however. In middle adulthood, consumption, binge drinking, and alcohol‐related harms are increasing, driven largely by increases among women in their 30s and 40s. The trend of increases in consumption that are faster for women than for men appears to continue into older adult years (60 and older) across several studies. We conclude by addressing remaining gaps in the literature and offering directions for future research.     

The efficacy of disulfiram for the treatment of alcohol use disorder

Background: Alcohol use disorders (AUD) involving hazardous, harmful, and addictive misuse of alcohol are widespread in most parts of the world. The aim of this study was to review the effect of disulfiram in the treatment of patients with AUD. The effect of disulfiram was evaluated according to the primary outcome of an intake of alcohol below 30 and 20 g/d for men and women, respectively, as well as secondary outcomes such as days until relapse, alcohol intake, and numbers of drinking days. Methods: A systematic review of the literature was conducted using MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL). Results: Eleven randomized controlled trials were included with a total of 1,527 patients. They compared disulfiram treatment with placebo, none or other abstinence‐supportive treatments. Overall, 6 studies reported of a significant better effect on abstinence for patients treated with disulfiram. Six of 9 studies measuring secondary outcomes reported that patients treated with disulfiram had significantly more days until relapse and fewer drinking days, respectively. The quality of the included studies was moderate. Heterogeneity was significant in most of the meta‐analyses, but valid results were found regarding the effect of disulfiram versus placebo over 12 months and unsupervised disulfiram versus other or no treatment. The vast majority of significant studies were of shorter duration, while only 3 studies of 12 months were significant regarding more days until relapse and/or reduction in drinking days. Conclusions: Supervised treatment with disulfiram has some effect on short‐term abstinence and days until relapse as well as number of drinking days when compared with placebo, none, or other treatments for patients with alcohol dependency or abuse. Long‐term effect on abstinence has not been evaluated yet. However, there is a need for more homogeneous and high‐quality studies in the future regarding the efficacy of disulfiram.     

The Influence of Alcohol Drinking and Alcohol Use Disorders on Psychiatric Disorders and Suicidal Behavior

The present review reports on the influence of alcohol drinking and alcohol use disorders on psychiatric disorders and suicidal behaviour. The base of the study was previous reviews of the National Institute on Alcohol Abuse and Alcoholism publication Alcohol and Health in 1993 and by Helgason in 1996. Using a defined search strategy in Medline, another 42 articles from 1994 to 1996 were included in the comorbidity part and 19 in the suicidal part. Epidemio-logical and clinical studies confirm high comorbidity of substance use disorders and other mental disorders. Alcohol abuse worsens the course of psychiatric disorders. Light to moderate alcohol consumption has no documented positive effect on the course. Levels of risk consumption of alcohol in psychiatric disorders have not been well defined. One-fifth to one-third of increased deaths rate among alcoholics is explained by suicide. In countries with high alcohol consumption, the suicide rate is also high and is increasing with total increased alcohol consumption. Comorbidity is common among suicide victims, and substance use disorders is most frequently combined with depressive disorders. Interpersonal loss within 6 weeks before suicide is more often present among alcoholics than nonalcoholic suicide victims.