Incident Tuberculosis Infection is Associated with Alcohol use in Adults in Rural Uganda.

Data on alcohol use and incident Tuberculosis (TB) infection are needed. In adults aged 15+ in rural Uganda (N=49,585), estimated risk of incident TB infection was 29.2% with alcohol use vs. 19.2% without (RR: 1.49; 95%CI: 1.40-1.60). There is potential for interventions to interrupt transmission among people who drink alcohol.

Alcohol Consumption Among Persons Living with HIV: Perceptions, Messages and Interventions-A Qualitative Study at an HIV Treatment Clinic in South Western Uganda.

In Sub-Saharan Africa, efficacy trials of brief interventions to reduce unhealthy drinking among persons living with HIV (PLWH) have yielded mixed results. A better understanding of the perceptions of drinking, especially by PLWH, and how drinking is talked about at HIV treatment clinics in this setting, may guide more optimal designs for future trials. We conducted a qualitative study at an HIV treatment clinic in South Western Uganda to better understand perceptions of drinking, how drinking is talked about, and perceptions of interventions, especially a protocolled screening and brief intervention (SBI) for unhealthy drinking among PLWH. We conducted in-depth interviews with 17 PLWH who engaged in unhealthy drinking and 6 health workers, and one focus group discussion with 3 community advisory-board members. We performed manual preliminary data analysis and computer-assisted detailed thematic analysis to identify emergent themes. Four themes emerged: perceptions of alcohol use in the general population; perceptions of alcohol use in PLWH; interaction between PLWH and health workers about alcohol use; perceptions of interventions for unhealthy drinking including SBI. Unhealthy drinking was seen as a problem in the general population and among those with HIV, where it was negatively perceived. Communication about drinking was done by counselors, but doctors participated in screening for unhealthy alcohol use. Messages about drinking covered reduction and abstinence. Participants expressed positive attitudes towards SBI and preference for person-delivered SBI over technological alternatives. A protocolled SBI for unhealthy alcohol use among PLWH would be well-received but successful implementation may depend on mode of delivery.

Participant perspectives on incentives for TB preventative therapy adherence and reduced alcohol use: A qualitative study.

Economic incentives to promote health behavior change are highly efficacious for substance use disorders as well as increased medication adherence. Knowledge about participants' experiences with and perceptions of incentives is needed to understand their mechanisms of action and optimize future incentive-based interventions. The Drinkers' Intervention to Prevent Tuberculosis (DIPT) trial enrolled people with HIV (PWH) in Uganda with latent tuberculosis and unhealthy alcohol use in a 2x2 factorial trial that incentivized recent alcohol abstinence and isoniazid (INH) adherence on monthly urine testing while on INH preventive therapy. We interviewed 32 DIPT study participants across trial arms to explore their perspectives on this intervention. Participants described 1) satisfaction with incentives of sufficient size that allowed them to purchase items that improved their quality of life, 2) multiple ways in which incentives were motivating, from gamification of "winning" through support of pre-existing desire to improve health to suggesting variable effects of extrinsic and intrinsic motivation, and 3) finding value in learning results of increased clinical monitoring. To build effective incentive programs to support both reduced substance use and increased antimicrobial adherence, we recommend carefully selecting incentive magnitude as well as harnessing both intrinsic motivation to improve health and extrinsic reward of target behavior. In addition to these participant-described strengths, incorporating results of clinical monitoring related to the incentive program that provide participants more information about their health may also contribute to health-related empowerment.

Pilot Trial Results of Mlambe: An Economic and Relationship-Strengthening Intervention to Address Heavy Drinking and Adherence to Antiretroviral Therapy in Malawi.

We evaluated the feasibility, acceptability, and preliminary efficacy of an economic and relationship-strengthening intervention to reduce heavy alcohol use among couples living with HIV in Malawi (Mlambe). Mlambe consisted of training on financial literacy and relationship skills, combined with 1:1 matched savings accounts to invest in an income-generating activity. In a randomized controlled trial, we compared Mlambe to enhanced usual care (EUC). We enrolled 78 married couples having a partner on antiretroviral therapy (ART) who reported heavy alcohol use based on the AUDIT-C. Using targets of 75%, primary outcomes included retention rates at 10 and 15-months, session attendance rates, and satisfaction with Mlambe. Exploratory outcomes were heavy alcohol use (AUDIT-C and/or PEth positive), number of drinking days in the past month, AUDIT-C score, optimal adherence to ART (95% or higher), and viral suppression. We exceeded our targets for feasibility and acceptability metrics. Retention rates were 96% at 15-months. Session attendance and satisfaction levels were both 100%. From baseline to 15-months, Mlambe participants reported decreases in mean number of drinking days (from 6.8 to 2.1) and AUDIT-C scores (from 7.5 to 3.1); while ART adherence rates improved across the same period (from 63.2 to 73.9%). Participants in Mlambe, as compared to those in EUC, had lower rates of heavy alcohol use (89.5% vs. 97.2%) and higher rates of viral suppression (100% vs. 91.9%) at 10-months. Differences between arms were not statistically significant in this small pilot study. Mlambe was highly feasible and acceptable, and shows promise for reducing heavy alcohol use and viral non-suppression among couples with HIV in a larger efficacy study.

Association between smoking and lack of HIV virological suppression in a cross-sectional study of persons with HIV on antiretroviral therapy in Uganda.

BACKGROUND: Smoking and alcohol use frequently co-occur and are the leading causes of preventable death in sub-Saharan Africa (SSA) and are common among people living with HIV (PLWH). While alcohol use has been shown to be associated with reduced adherence to antiretroviral treatment (ART), which may affect HIV viral suppression, the independent effect of smoking on HIV outcomes in SSA is unknown. We aimed to 1) describe the prevalence of current smoking and correlates of smoking; 2) assess the association of smoking with viral suppression, adjusting for level of alcohol use; 3) explore the relationship between smoking and CD4 cell count <350 cells/mm3, among participants who are virally suppressed. METHODS: We analyzed data from the Drinkers Intervention to Prevent Tuberculosis (DIPT) and the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) studies conducted in Southwest Uganda. The studies enrolled PLWH who were on ART for at least 6 months and co-infected with latent tuberculosis and dominated with participants who had unhealthy alcohol use. Current smoking (prior 3 months) was assessed by self-report. Alcohol use was assessed using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C, modified for prior 3 months) and phosphatidylethanol (PEth), an alcohol biomarker. We used logistic regression to estimate the cross-sectional association between smoking and lack of virological suppression (≥40 copies/ml), adjusting for level of alcohol use and other covariates, and to examine the association between smoking and CD4 cell counts among PLWH with viral suppression. RESULTS: Of the 955 participants enrolled from 2017 to 2021 who had viral load (VL) results, 63% were men, median age was 40 years (interquartile range [IQR] 32-47), 63% engaged in high/very high-risk alcohol use (AUDIT-C≥6 or PEth≥200 ng/mL), and 22% reported smoking in the prior 3 months. Among 865 participants (91%) with viral suppression and available CD4 count, 11% had a CD4 cell count <350 cells/mm3. In unadjusted and adjusted analyses, there was no evidence of an association between smoking and lack of virological suppression nor between smoking and CD4 count among those with viral suppression. CONCLUSIONS: The prevalence of smoking was high among a study sample of PLWH in HIV care with latent TB in Southwest Uganda in which the majority of persons engaged in alcohol use. Although there was no evidence of an association between smoking and lack of virological suppression, the co-occurrence of smoking among PLWH who use alcohol underscores the need for targeted and integrated approaches to reduce their co-existence and improve health.

A Qualitative Exploration of Intimate Partner Violence Among HIV/TB Coinfected Persons With Problematic Alcohol Use Participating in an Incentive-Based Alcohol/Medication Adherence Intervention in Uganda During COVID-19.

In Uganda, four in ten women report experiencing intimate partner violence (IPV) in the past year. Salient drivers of IPV in sub-Saharan Africa include stress related to household finances, alcohol use, and partner infidelity. We conducted 42 interviews with participants (n = 32) in the Drinkers' Intervention to Prevent Tuberculosis (DIPT) study which included economic incentives, and their partners (n = 10) to understand how participating in DIPT during COVID-19 lockdown restrictions impacted relationship dynamics in intimate partnerships. Our findings highlight the need to develop policies to address root causes of IPV and to ensure continuity of IPV services in future pandemics. Policy and programming recommendations based on study results are presented.

The Relationship between Age at Initiation of Regular Drinking of Alcohol and Viral Suppression Status, and Depression Symptoms Among People Living with HIV in South-Western Uganda.

Alcohol use is an important factor in achieving and maintaining viral suppression and optimal mental health among persons with HIV (PWH), however, the effect of age at first regular drinking on viral suppression and depression remains poorly understood. Here, using secondary data from the Alcohol Drinkers' Exposure to Preventive Therapy for Tuberculosis (ADEPT-T) study, we used logistic regression analyses to explore whether there is an association between age at first regular drinking and viral suppression (< 40 copies/ml), or presence of depressive symptoms (Center for Epidemiologic Studies Depression, CES-D ≥ 16) among 262 PWH. The median age at first regular drinking was 20.5 years (IQR: 10), with high proportions starting under age 12 (12.2%) and as teens (13.4%). The majority had an undetectable viral load (91.7%) and 11% had symptoms of probable depression. We found no significant association between age at first regular drinking and viral suppression (i.e., child (aOR = 0.76 95%CI: 0.18, 3.26), adolescent (aOR = 0.74 95%CI: 0.18, 2.97) and young adult (aOR = 1.27 95%CI: 0.40, 3.97)) nor with depressive symptoms (i.e., child (aOR = 0.72 95%CI: 0.19, 2.83), adolescent (aOR = 0.59 95%CI: 0.14, 2.50) and young adult (aOR = 0.57 95%CI: 0.22, 1.53)). Age at first regular drinking among PWH did not appear to be associated with either viral suppression or the presence of depressive symptoms, suggesting interventions may best be focused on the harmful effects of current alcohol use.

Pivoting from in-person to phone survey assessment of alcohol and substance use: effects on representativeness in a United States prospective cohort of women living with and without HIV.

Background: Many clinical and population-based research studies pivoted from in-person assessments to phone-based surveys due to the COVID-19 pandemic. The impact of these transitions on survey response remains understudied, especially for people living with HIV. Given that there are gender-specific trends in alcohol and substance use, it is particularly important to capture these data for women.Objective: Identify factors associated with responding to an alcohol and substance use phone survey administered during the COVID-19 pandemic in the Women's Interagency HIV Study, a multicenter US prospective cohort of women living with and without HIV.Methods: We used multivariable logistic regression to assess for associations of pre-pandemic (April-September 2019) sociodemographic factors, HIV status, housing status, depressive symptoms, alcohol use, and substance use with response to an early-pandemic (August-September 2020) phone survey.Results: Of 1,847 women who attended an in-person visit in 2019, 78% responded to a phone survey during the pandemic. The odds of responding were lower for women of Hispanic ethnicity (aOR 0.47 95% CI 0.33-0.66, ref=Black/African American) and those who reported substance use (aOR 0.63 95% CI 0.41-0.98). By contrast, the odds were higher for White women (aOR 1.64 95% CI 1.02-2.70, ref=Black/African American) and those with stable housing (aOR 1.74 95% CI 1.24-2.43).Conclusions: Pivoting from an in-person to phone-administered alcohol and substance use survey may lead to underrepresentation of key subpopulations of women who are often neglected in substance use and HIV research. As remote survey methods become more common, investigators need to ensure that the study population is representative of the target population.

Effects of Maternal HIV Infection and Alcohol Use in Pregnancy on Birth Outcomes in Uganda.

Alcohol use and HIV infection are prevalent in sub-Saharan Africa (sSA), and both are associated with low birth weight. Yet, few studies have evaluated the combined effects of maternal HIV infection and alcohol use on birth outcomes. We analyzed data from a prospective cohort study of HIV-related placental changes in Ugandan women. We defined alcohol use as self-reported alcohol use within the last year, using the AUDIT questionnaire and used linear and logistic regression to measure associations between maternal alcohol use, HIV serostatus, and birth weight. In a subsample, we measured alcohol exposure using phosphatidylethanol (PEth) in neonatal heelstick dried blood spots to confirm maternal alcohol use. Of 352 participants, 176 (50%) were women with HIV (WHIV). Three of 176 (2%) HIVuninfected women and 17/176 (10%) of WHIV self-reported alcohol use (P = 0.002). Maternal HIV infection was associated with lower birth weight (ß = -0.12, 95% CI [-0.20, -0.02], P = 0.02), but self-reported alcohol use was not (ß = 0.06, 95% CI [-0.15, 0.26], P = 0.54), and the interaction between HIV serostatus and alcohol use was not significant (P = 0.13). Among the PEth subsample, neither HIV status nor PEthconfirmed alcohol use were associated with low birth weight. Maternal HIV infection was associated with lower birth weight, but alcohol use was not, and there was no significant interaction between maternal HIV infection and alcohol use. Alcohol use was more prevalent in WHIV and under-reporting was common. A larger study of the effects of laboratory-confirmed alcohol and HIV exposure on birth outcomes is warranted.

Tailoring the pore design of embroidered structures by melt electrowriting to enhance the cell alignment in scaffold-based tendon reconstruction.

Tissue engineering of ligaments and tendons aims to reproduce the complex and hierarchical tissue structure while meeting the biomechanical and biological requirements. For the first time, the additive manufacturing methods of embroidery technology and melt electrowriting (MEW) were combined to mimic these properties closely. The mechanical benefits of embroidered structures were paired with a superficial micro-scale structure to provide a guide pattern for directional cell growth. An evaluation of several previously reported MEW fiber architectures was performed. The designs with the highest cell orientation of primary dermal fibroblasts were then applied to embroidery structures and subsequently evaluated using human adipose-derived stem cells (AT-MSC). The addition of MEW fibers resulted in the formation of a mechanically robust layer on the embroidered scaffolds, leading to composite structures with mechanical properties comparable to those of the anterior cruciate ligament. Furthermore, the combination of embroidered and MEW structures supports a higher cell orientation of AT-MSC compared to embroidered structures alone. Collagen coating further promoted cell attachment. Thus, these investigations provide a sound basis for the fabrication of heterogeneous and hierarchical synthetic tendon and ligament substitutes.

Effect of a brief alcohol counselling intervention on HIV viral suppression and alcohol use among persons with HIV and unhealthy alcohol use in Uganda and Kenya: a randomized controlled trial.

INTRODUCTION: Unhealthy alcohol use significantly contributes to viral non-suppression among persons with HIV (PWH). It is unknown whether brief behavioural interventions to reduce alcohol use can improve viral suppression among PWH with unhealthy alcohol use in sub-Saharan Africa (SSA). METHODS: As part of the SEARCH study (NCT04810650), we conducted an individually randomized trial in Kenya and Uganda of a brief, skills-based alcohol intervention among PWH with self-reported unhealthy alcohol use (Alcohol Use Disorders Identification Test-Consumption [AUDIT-C], prior 3 months, ≥3/female; ≥4/male) and at risk of viral non-suppression, defined as either recent HIV viral non-suppression (≥400 copies/ml), missed visits, out of care or new diagnosis. The intervention included baseline and 3-month in-person counselling sessions with interim booster phone calls every 3 weeks. The primary outcome was HIV viral suppression (<400 copies/ml) at 24 weeks, and the secondary outcome was unhealthy alcohol use, defined by AUDIT-C or phosphatidylethanol (PEth), an alcohol biomarker, ≥50 ng/ml at 24 weeks. RESULTS: Between April and September 2021, 401 persons (198 intervention, 203 control) were enrolled from HIV clinics in Uganda (58%) and Kenya (27%) and alcohol-serving venues in Kenya (15%). At baseline, 60% were virally suppressed. Viral suppression did not differ between arms at 24 weeks: suppression was 83% in intervention and 82% in control arms (RR: 1.01, 95% CI: 0.93-1.1). Among PWH with baseline viral non-suppression, 24-week suppression was 73% in intervention and 64% in control arms (RR 1.15, 95% CI: 0.93-1.43). Unhealthy alcohol use declined from 98% at baseline to 73% in intervention and 84% in control arms at 24 weeks (RR: 0.86, 95% CI: 0.79-0.94). Effects on unhealthy alcohol use were stronger among women (RR 0.70, 95% CI: 0.56-0.88) than men (RR 0.93, 95% CI: 0.85-1.01) and among participants with a baseline PEth⩽200 ng/ml (RR 0.68, 95% CI: 0.53-0.87) versus >200 ng/ml (RR 0.97, 95% CI: 0.92-1.02). CONCLUSIONS: In a randomized trial of 401 PWH with unhealthy alcohol use and risk for viral non-suppression, a brief alcohol intervention reduced unhealthy alcohol use but did not affect viral suppression at 24 weeks. Brief alcohol interventions have the potential to improve the health of PWH in SSA by reducing alcohol use, a significant driver of HIV-associated co-morbidities.

Financial incentives for reduced alcohol use and increased isoniazid adherence during tuberculosis preventive therapy among people with HIV in Uganda: an open-label, factorial randomised controlled trial.

BACKGROUND: Alcohol use is common among people with HIV and is a risk factor for tuberculosis disease and non-adherence to isoniazid preventive therapy (IPT). Few interventions exist to reduce alcohol use and increase IPT adherence in sub-Saharan Africa. The aim of this study was to test the hypothesis that financial incentives conditional on point-of-care negative urine alcohol biomarker testing and positive urine isoniazid testing would reduce alcohol use and increase isoniazid adherence, respectively, in people with HIV who have latent tuberculosis infection and hazardous alcohol use. METHODS: We conducted an open-label, 2×2 factorial randomised controlled trial in Uganda. Eligible for the study were non-pregnant HIV-positive adults (aged ≥18 years) prescribed antiretroviral therapy for at least 6 months, with current heavy alcohol use confirmed by urine ethyl glucuronide (biomarker of recent alcohol use) and a positive Alcohol Use Disorders Identification Test-Consumption (AUDIT-C; ≥3 for women, ≥4 for men) for the past 3 months' drinking, no history of active tuberculosis, tuberculosis treatment, or tuberculosis preventive therapy, and a positive tuberculin skin test. We randomly assigned participants (1:1:1:1) initiating 6 months of IPT to: no incentives (group 1); or incentives for recent alcohol abstinence (group 2), isoniazid adherence (group 3), or both (group 4). Escalating incentives were contingent on monthly point-of-care urine tests negative for ethyl glucuronide (groups 2 and 4), or positive on IsoScreen (biomarker of recent isoniazid use; groups 3 and 4). The primary alcohol outcome was non-hazardous use by self-report (AUDIT-C <3 for women, <4 for men) and phosphatidylethanol (PEth; past-month alcohol biomarker) <35 ng/mL at 3 months and 6 months. The primary isoniazid adherence outcome was more than 90% bottle opening of days prescribed. We performed intention-to-treat analyses. This trial is registered with ClinicalTrials.gov (NCT03492216), and is complete. FINDINGS: From April 16, 2018, to Aug 2, 2021, 5508 people were screened, of whom 680 were randomly assigned: 169 to group 1, 169 to group 2, 170 to group 3, and 172 to group 4. The median age of participants was 39 years (IQR 32-47), 470 (69%) were male, 598 (90%) of 663 had HIV RNA viral loads of less than 40 copies per mL, median AUDIT-C score was 6 (IQR 4-8), and median PEth was 252 ng/mL (IQR 87-579). Among 636 participants who completed the trial with alcohol use endpoint measures (group 1: 152, group 2: 159, group 3: 161, group 4: 164), non-hazardous alcohol use was more likely in the groups with incentives for alcohol abstinence (groups 2 and 4) versus no alcohol incentives (groups 1 and 3): 57 (17·6%) of 323 versus 31 (9·9%) of 313, respectively; adjusted risk difference (aRD) 7·6% (95% CI 2·7 to 12·5, p=0·0025). Among 656 participants who completed the trial with isoniazid adherence endpoint measures (group 1: 158, group 2: 163, group 3: 168, group 4: 167), incentives for isoniazid adherence did not increase adherence: 244 (72·8%) of 335 in the isoniazid incentive groups (groups 3 and 4) versus 234 (72·9%) of 321 in the no isoniazid incentive groups (groups 1 and 2); aRD -0·2% (95% CI -7·0 to 6·5, p=0·94). Overall, 53 (8%) of 680 participants discontinued isoniazid due to grade 3 or higher adverse events. There was no significant association between randomisation group and hepatotoxicity resulting in isoniazid discontinuation, after adjusting for sex and site. INTERPRETATION: Escalating financial incentives contingent on recent alcohol abstinence led to significantly lower biomarker-confirmed alcohol use versus control, but incentives for recent isoniazid adherence did not lead to changes in adherence. The alcohol intervention was efficacious despite less intensive frequency of incentives and clinic visits than traditional programmes for substance use, suggesting that pragmatic modifications of contingency management for resource-limited settings can have efficacy and that further evaluation of implementation is merited. FUNDING: National Institute on Alcohol Abuse and Alcoholism. TRANSLATION: For the Runyankole translation of the abstract see Supplementary Materials section.

Stakeholder perspectives on the Kisoboka intervention: A behavioral and structural intervention to reduce hazardous alcohol use and improve HIV care engagement among men living with HIV in Ugandan fishing communities.

BACKGROUND: East Africa's fishing communities experience a high burden of two interrelated and frequently co-occurring health issues: HIV and hazardous alcohol use. Nearly two-thirds of Ugandan fisherfolk men meet the criteria for harmful alcohol use. We developed a multilevel intervention to reduce hazardous alcohol use and improve HIV care engagement among fisherfolk men living with HIV (LWHIV) in Wakiso district, Uganda. METHODS: This is a qualitative study of stakeholder perspectives on the appropriateness, acceptability, and feasibility of a multilevel intervention for fisherfolk men LWHIV. The proposed intervention, Kisoboka ("It is possible!"), combines a structural component [changing the mode of work payments from cash to mobile money] with a behavioral component [motivational interviewing-based counseling combined with content using behavioral economic principles to promote behavior change]. We conducted one focus group (n=7) and eight in-depth interviews with fisherfolk men LWHIV and 19 key informant (KI) interviews with health workers, employers, and community leaders. These explored the appropriateness, acceptability, and feasibility of specific key intervention components. RESULTS: Overall, stakeholders' perspectives supported high intervention acceptability and perceived appropriateness of the proposed intervention. It was perceived to be feasible with some caveats of recommendations for overcoming potential implementation challenges identified (e.g., having a friend assist with documenting savings and alcohol use if an individual was unable to write themselves) which are discussed. CONCLUSION: This work highlights the potential of the Kisoboka intervention and the importance of early engagement of key stakeholders in the intervention development process to ensure appropriateness, acceptability, feasibility, and socio-cultural fit.

Could an Anterior Cruciate Ligament Be Tissue-Engineered from Silk?

Silk has a long history as an exclusive textile, but also as a suture thread in medicine; nowadays, diverse cell carriers are manufactured from silk. Its advantages are manifold, including high biocompatibility, biomechanical strength and processability (approved for nearly all manufacturing techniques). Silk's limitations, such as scarcity and batch to batch variations, are overcome by gene technology, which allows for the upscaled production of recombinant "designed" silk proteins. For processing thin fibroin filaments, the sericin component is generally removed (degumming). In contrast to many synthetic biomaterials, fibroin allows for superior cell adherence and growth. In addition, silk grafts demonstrate superior mechanical performance and long-term stability, making them attractive for anterior cruciate ligament (ACL) tissue engineering. Looking at these promising properties, this review focusses on the responses of cell types to silk variants, as well as their biomechanical properties, which are relevant for ACL tissue engineering. Meanwhile, sericin has also attracted increasing interest and has been proposed as a bioactive biomaterial with antimicrobial properties. But so far, fibroin was exclusively used for experimental ACL tissue engineering approaches, and fibroin from spider silk also seems not to have been applied. To improve the bone integration of ACL grafts, silk scaffolds with osteogenic functionalization, silk-based tunnel fillers and interference screws have been developed. Nevertheless, signaling pathways stimulated by silk components remain barely elucidated, but need to be considered during the development of optimized silk cell carriers for ACL tissue engineering.

Association of Alcohol Consumption With CD4 Recovery After Antiretroviral Therapy Initiation in St. Petersburg, Russia.

BACKGROUND: Delayed CD4 recovery after initiating antiretroviral therapy (ART) is a novel potential mechanism by which alcohol consumption leads to increased morbidity and mortality in people with HIV. We hypothesized that alcohol consumption at ART initiation is associated with slower CD4 recovery. METHODS: We retrospectively analyzed 2 pooled longitudinal alcohol/HIV cohorts (2014-2019) in St. Petersburg, Russia. Eligible participants initiated the first ART during parent studies; had alcohol consumption assessed by the blood biomarker, phosphatidylethanol (PEth), at the last research visit before ART initiation; and had ≥1 CD4 count measurement before and after initiating ART. Participants were stratified by low, moderate, and high PEth (<8, 8-80, and >80 ng/mL, respectively). We used random-effects piecewise linear regression models to estimate CD4 recovery, defined as CD4 count change per 30 days after ART initiation, by the alcohol group. RESULTS: Of 60 eligible participants, median age was 34 years and 28% were female. The median pre-ART PEth in the low, moderate, and high PEth groups were <8, 23, and 232 ng/mL, respectively. After starting ART, the CD4 count increased by 13.60 cells/mm3/mo (95% CI: 0.33 to 26.87) with low PEth, 0.93 cells/mm3/mo (95% CI: -6.18 to 8.04) with moderate PEth, and 2.33 cells/mm3/mo (95% CI: -3.44 to 8.09) with high PEth. CONCLUSIONS: Among Russians with HIV, we observed faster CD4 recovery after ART initiation in those with low alcohol consumption compared with those with moderate and high alcohol consumption, as assessed by PEth. This analysis provides further evidence for the possible value of alcohol reduction interventions for people with HIV who are initiating ART.

Phosphatidylethanol vs Transdermal Alcohol Monitoring for Detecting Alcohol Consumption Among Adults.

Importance: Alcohol biomarkers can improve detection of heavy alcohol use in clinical care, yet cutoffs for phosphatidylethanol (PEth), a blood biomarker, have not been established. Objective: To determine the optimal cutoff for PEth for heavy alcohol consumption in a study of middle-age and older adults. Design, Setting, and Participants: This was a 4-week diagnostic study of adults with paroxysmal atrial fibrillation (AF) and current alcohol consumption, recruited from general cardiology and cardiac electrophysiology outpatient clinics from September 2014 to September 2019. Data were analyzed from October 2021 to March 2022. Main Outcomes and Measures: The main aim was to determine the optimal PEth cutoff for heavy alcohol consumption, using the Secure Continuous Remote Alcohol Monitor (SCRAM) to measure transdermal alcohol. Area under the curve (AUC) for PEth-detected compared with SCRAM-detected heavy alcohol consumption in any week over the prior 4 weeks (ie, ≥3 [women] and ≥4 [men] episodes) or any estimated breath alcohol of 0.08% or greater in any week, and the PEth cutoff was calculated using the Youden J statistic. Similar analyses were conducted comparing PEth with individual drinks reported by pressing an event monitor, retrospective self-report via the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), and using 2-week look-backs. Results: In this diagnostic study of 64 patients with both PEth and SCRAM measures over 4 weeks (54 [84.4%] men; mean age, 65.5 [95% CI, 62.6-68.5] years; 51 [79.7%] White), 31 (48.4%) had any SCRAM-detected heavy alcohol consumption over the 4 weeks, and the median (IQR) PEth at 4 weeks was 23 ng/mL (

Understanding Patients' Experiences with a Brief Alcohol Reduction Intervention among People Living with HIV in Uganda: A Qualitative Study.

Background: Brief alcohol reduction interventions for people living with HIV (PLWH) have resulted in mixed findings with some studies showing null or limited treatment effects. To better understand factors that may contribute to their success or failure, this qualitative study sought to explore participants' experiences in a randomized trial (RCT) of a brief counseling-based alcohol reduction intervention, including challenges that may have impeded alcohol reduction. Methods: We conducted in-depth semi-structured interviews with 24 PLWH engaging in unhealthy alcohol use, who were enrolled in an RCT to reduce alcohol consumption conducted in southwestern Uganda in 2019-2020 (NCT03928418). We used a collaborative thematic approach to analyze data from transcribed and translated audio recordings. Results: Perceived benefits of the intervention included increased awareness of alcohol use and its impact on personal finances, the relationship between alcohol use and violence, and a commitment to drinking reduction. Participants experienced several barriers to decreasing their alcohol use, including: prevailing social norms about alcohol use, lack of social support, and economic and social consequences of the COVID-19 pandemic. Conclusion: Factors in the immediate contexts of PLWH in low-income settings, including social norms influencing alcohol consumption and lack of social support, may impede the impact of alcohol reduction interventions, especially during times of stress such as the COVID-19 pandemic.

Efficacy of alcohol reduction interventions among people with HIV as evaluated by self-report and a phosphatidylethanol (PEth) outcome: protocol for a systematic review and individual participant data meta-analysis.

INTRODUCTION: Unhealthy alcohol use is associated with a range of adverse outcomes among people with HIV (PWH). Testing the efficacy and promoting the availability of effective interventions to address unhealthy alcohol use among PWH is thus a priority. Alcohol use outcomes in intervention studies are often measured by self-report alone, which can lead to spurious results due to information biases (eg, social desirability). Measuring alcohol outcomes objectively through biomarkers, such as phosphatidylethanol (PEth), in addition to self-report has potential to improve the validity of intervention studies. This protocol outlines the methods for a systematic review and individual participant data meta-analysis that will estimate the efficacy of interventions to reduce alcohol use as measured by a combined categorical self-report/PEth variable among PWH and compare these estimates to those generated when alcohol is measured by self-report or PEth alone. METHODS AND ANALYSIS: We will include randomised controlled trials that: (A) tested an alcohol intervention (behavioural and/or pharmacological), (B) enrolled participants 15 years or older with HIV; (C) included both PEth and self-report measurements, (D) completed data collection by 31 August 2023. We will contact principal investigators of eligible studies to inquire about their willingness to contribute data. The primary outcome variable will be a combined self-report/PEth alcohol categorical variable. Secondary outcomes will include PEth alone, self-report alone and HIV viral suppression. We will use a two-step meta-analysis and random effects modelling to estimate pooled treatment effects; I2 will be calculated to evaluate heterogeneity. Secondary and sensitivity analyses will explore treatment effects in adjusted models and within subgroups. Funnel plots will be used to explore publication bias. ETHICS AND DISSEMINATION: The study will be conducted with deidentified data from completed randomised controlled trials and will be considered exempt from additional ethical approval. Results will be disseminated through peer-reviewed publications and international scientific meetings. PROSPERO REGISTRATION NUMBER: CRD42022373640.

Anatomical Tissue Engineering of the Anterior Cruciate Ligament Entheses.

The firm integration of anterior cruciate ligament (ACL) grafts into bones remains the most demanding challenge in ACL reconstruction, since graft loosening means graft failure. For a functional-tissue-engineered ACL substitute to be realized in future, robust bone attachment sites (entheses) have to be re-established. The latter comprise four tissue compartments (ligament, non-calcified and calcified fibrocartilage, separated by the tidemark, bone) forming a histological and biomechanical gradient at the attachment interface between the ACL and bone. The ACL enthesis is surrounded by the synovium and exposed to the intra-articular micromilieu. This review will picture and explain the peculiarities of these synovioentheseal complexes at the femoral and tibial attachment sites based on published data. Using this, emerging tissue engineering (TE) strategies addressing them will be discussed. Several material composites (e.g., polycaprolactone and silk fibroin) and manufacturing techniques (e.g., three-dimensional-/bio-printing, electrospinning, braiding and embroidering) have been applied to create zonal cell carriers (bi- or triphasic scaffolds) mimicking the ACL enthesis tissue gradients with appropriate topological parameters for zones. Functionalized or bioactive materials (e.g., collagen, tricalcium phosphate, hydroxyapatite and bioactive glass (BG)) or growth factors (e.g., bone morphogenetic proteins [BMP]-2) have been integrated to achieve the zone-dependent differentiation of precursor cells. However, the ACL entheses comprise individual (loading history) asymmetric and polar histoarchitectures. They result from the unique biomechanical microenvironment of overlapping tensile, compressive and shear forces involved in enthesis formation, maturation and maintenance. This review should provide a road map of key parameters to be considered in future in ACL interface TE approaches.

HIV stigma and disclosure of alcohol use to physicians: examining the mediating role of depression among persons living with HIV.

Alcohol use among persons living with HIV (PWH) can lead to poor disease outcomes. Disclosure of alcohol consumption to physicians is critical to inform HIV care. HIV stigma is associated with poor care engagement, and this relationship is partially mediated by depression. However, less is known about how HIV stigma and depression affect reporting of alcohol use to care providers. We used baseline data from an HIV intervention trial of 330 adult PWH in Baltimore, MD. We fit a path model to examine whether HIV stigma was associated with increased depression symptoms and whether higher levels of depression were, in turn, associated with underreporting of alcohol use to physicians. Among PWH reporting past 6-month alcohol use (n = 182, 55%), 64% met symptom criteria for probable depression, 58% met criteria for hazardous drinking, and 10% reported not disclosing alcohol use to their physician. HIV stigma was associated with higher levels of depression (ß = 0.99, p < .0001); depression was associated with a lower likelihood of alcohol disclosure (ß = -0.04, p < .0001); and depression mediated the indirect pathway from stigma to alcohol disclosure (ß = -0.04, p < .01). Methods to augment or strengthen alcohol self-report may be useful in HIV care, particularly among PWH experiencing HIV stigma and depression.