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Background and Aims: There is currently no standard of care for pharmacological treatment of amphetamine‐type stimulant (ATS) use disorder (ATSUD). This systematic review with meta‐analysis (PROSPERO CRD42022354492) aimed to pool results from randomized placebo‐controlled trials (RCTs) to evaluate efficacy and safety of prescription psychostimulants (PPs) for ATSUD. Methods: Major indexing sources and trial registries were searched to include records published before 29 August 2022. Eligible studies were RCTs evaluating efficacy and safety of PPs for ATSUD. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. Risk ratio (RR) and risk difference were calculated for random‐effect meta‐analysis of dichotomous variables. Mean difference and standardized mean difference (SMD) were calculated for random‐effect meta‐analysis of continuous variables. Results: Ten RCTs (n = 561 participants) were included in the meta‐analysis. Trials studied methylphenidate (n = 7), with daily doses of 54–180 mg, and dextroamphetamine (n = 3), with daily doses of 60–110 mg, for 2–24 weeks. PPs significantly decreased end‐point craving [SMD −0.29; 95% confidence interval (CI) = −0.55, −0.03], while such a decrease did not reach statistical significance for ATS use, as evaluated by urine analysis (UA) (RR = 0.93; 95% CI = 0.85–1.01). No effect was observed for self‐reported ATS use, retention in treatment, dropout following adverse events, early‐stage craving, withdrawal and depressive symptoms. In a sensitivity analysis, treatment was associated with a significant reduction in UA positive for ATS (RR = 0.89; 95% CI = 0.79–0.99) after removing studies with a high risk of bias. In subgroup analyses, methylphenidate and high doses of PPs were negatively associated with ATS use by UA, while higher doses of PPs and treatment duration (≥ 20 weeks) were positively associated with longer retention. Conclusions: Among individuals with amphetamine‐type stimulant use disorder, treatment with prescription psychostimulants may decrease ATS use and craving. While effect size is limited, it may increase with a higher dosage of medications. [ABSTRACT FROM AUTHOR]

Objective: To investigate the demographic characteristics, substance use, and self‐rated health of people entering treatment in New South Wales public health services for alcohol, amphetamine‐type stimulants, cannabis, cocaine, or opioids use, by principal drug of concern. Design: Baseline findings of a cohort study; analysis of data in patient electronic medical records and NSW minimum data set for drug and alcohol treatment services. Setting, participants: People completing initial Australian Treatment Outcomes Profile (ATOP) assessments on entry to publicly funded alcohol and other drug treatment services in six NSW local health districts/networks, 1 July 2016 – 30 June 2019. Main outcome measures: Socio‐demographic characteristics, and substance use and self‐rated health (psychological, physical, quality of life) during preceding 28 days, by principal drug of concern. Results: Of 14 087 people included in our analysis, the principal drug of concern was alcohol for 6051 people (43%), opioids for 3158 (22%), amphetamine‐type stimulants for 2534 (18%), cannabis for 2098 (15%), and cocaine for 246 (2%). Most people commencing treatment were male (9373, 66.5%), aged 20–39 years (7846, 50.4%), and were born in Australia (10 934, 86.7%). Polysubstance use was frequently reported, particularly by people for whom opioids or amphetamine‐type stimulants were the principal drugs of concern. Large proportions used tobacco daily (53–82%, by principal drug of concern group) and reported poor psychological health (47–59%), poor physical health (32–44%), or poor quality of life (43–52%). Conclusions: The prevalence of social disadvantage and poor health is high among people seeking assistance with alcohol, amphetamine‐type stimulants, cannabis, cocaine, or opioids use problems. Given the differences in these characteristics by principal drug of concern, health services should collect comprehensive patient information during assessment to facilitate more holistic, tailored, and person‐centred care. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Discussion and Conclusions Fielding greater than 100,000 calls annually, telephone helplines are an important point of entry to alcohol and other drug (AOD) support and services in Australia. Methamphetamine and emerging drugs can present a particular challenge for this workforce. We sought to identify training needs for these services, so that appropriate targeted resources can be developed.We distributed an anonymous, online, cross‐sectional survey to helpline staff from New South Wales, Queensland, South Australia, Victoria and Western Australia. Based on the WHO Hennessy‐Hicks training needs analysis tool, participants were asked: to rate on a 7‐point likert scale the importance of a topic to their practice and how well they perform in relation to the topic; open‐ended questions specifying their own self‐perceived training needs; and demographic data.Of 50 participants, 29 completed the full survey (median age 49 [IQR 30–57.5]; median time working in AOD sector 6 years [IQR 1–20]). The results identified a need for: practical community‐informed population relevant information for culturally and linguistically diverse populations and Aboriginal and Torres Strait Islander peoples for calls relating to methamphetamine and emerging drugs of concern; training and resources with a particular focus on families and friends of people who use methamphetamine and emerging drugs; and readily accessible up‐to‐date information on new and emerging drugs and treatment of related disorders.This training needs analysis provides a structured approach to supporting the first‐line AOD counsellors to provide up‐to‐date and accurate information to assist Australians seeking information, support and advice. [ABSTRACT FROM AUTHOR]

Introduction: Amphetamine type substances (ATS) are commonly used by Australian alcohol and other drug service entrants. We describe demographic characteristics, patterns of ATS and other substance use, health and social conditions among clients entering New South Wales (NSW) public alcohol and other drug services. Methods: Retrospective cohort of 13,864 records across six health districts (2016–2019) for clients seeking substance use treatment. These districts service approximately 44% of the NSW population aged 15 years and over. Multivariate analysis was conducted on a subsample for whom full data were available (N = 9981). Data included NSW Minimum Data Set for drug and alcohol treatment services and Australian Treatment Outcomes Profile items. Results: Over the preceding 4 weeks, 77% (n = 10,610) of clients (N = 13,864) reported no recent ATS use, 15% (n = 2109) reported 'low frequency' (1–12 days) and 8% (n = 1145) 'high frequency' (13–28 days) use. ATS use was most common among people attending for ATS or opioids as primary drug of concern. A multinomial regression (N = 9981) identified that clients reporting recent arrest (aOR 1.74, 95% CI 1.36, 2.24), higher cannabis use frequency (aOR 1.01, 95% CI 1.00, 1.02), lower opioid use frequency (aOR 0.98, 95% CI 0.97, 0.99) and poorer quality of life (aOR 0.91, 95% CI 0.86, 0.97) were more likely to report 'high frequency' rather than 'low frequency' ATS use. Discussion and Conclusions: People who use ATS experience health and social issues that may require targeted responses. These should be integrated across all services, not only for clients with ATS as principal drug of concern. [ABSTRACT FROM AUTHOR]

Introduction: Management of a withdrawal syndrome following cessation of regular gamma‐hydroxybutyrate (GHB) use, and its precursors, can represent a clinical challenge due to rapid onset delirium and/or seizures. Severe GHB withdrawal can be characterised by persistent or worsening features despite increasing benzodiazepine doses and regular baclofen. Barbiturates, such as phenobarbital, are an appealing option in this context due to their unique GABA‐A receptor action. Case Series: This series describes the use of phenobarbital in 13 cases, 12 patients, across two hospitals in Sydney, Australia, with persistent or progressive GHB withdrawal despite benzodiazepine‐based management. A median cumulative dose of oral diazepam prior to commencing phenobarbital was 120 mg (range 80–255 mg). The median time from the last GHB use to the first dose of phenobarbital was 24 h (range 7–57 h). Eight cases received phenobarbital orally on a general ward and 5 intravenously in intensive care units. An improvement in GHB withdrawal symptoms was observed after phenobarbital in all cases and there were no adverse events related to phenobarbital. Discussion and Conclusion: This case series suggests that phenobarbital for the management of benzodiazepine‐resistant GHB withdrawal can be safe, even in general inpatient settings, and may avert the progression of delirium. Most data on the management of GHB withdrawal comes from case reports or series, such as this one. This highlights the need for prospective trials to establish an evidence base for therapeutic approaches, including validated measures of withdrawal severity and more information relating to the safe and effective dosing of phenobarbital. [ABSTRACT FROM AUTHOR]

Issues: Cessation of methamphetamine use may result in a characteristic withdrawal syndrome, no medication has been approved for this indication. This systematic review aims to assess the efficacy of pharmacotherapy for methamphetamine withdrawal, the first comprehensive meta‐analysis since 2008. Approach: MEDLINE (1966–2020), CINAHL (1982–2020), PsychINFO (1806–2020) and EMBASE (1947–2020) were systematically searched. Studies were included if they were randomised controlled trials (RCT) investigating pharmacological treatments for methamphetamine withdrawal, reviewing outcomes of treatment discontinuation, mental health outcomes, withdrawal symptoms (including craving) and patient safety. The relative risk (RR) and weighted mean difference (MD) were used to meta‐analyse dichotomous and continuous data respectively, with 95% confidence intervals. Risk of bias and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments were conducted. Key Findings: Nine RCTs of six medications (n = 242 participants) met inclusion criteria, however, only six trials of four medications (n = 186) could be meta‐analysed. Mean sample size across studies was 27 participants, and 88% of participants were male. The quality of evidence in this review varies from low to very low on GRADE assessments. Amineptine may reduce discontinuation rates (RR 0.22, 95% confidence interval [CI] 0.07, 0.72, p = 0.01), and improve global state (MD −0.49, 95% CI −0.80, −0.17), compared with placebo, however, this medication is no longer approved. No other medications improved any domain when compared with placebo. Due to lack of reporting safety profiles could not be established. Conclusions: There is insufficient evidence to indicate any medication is effective for the treatment of methamphetamine withdrawal. The poor quality of the evidence indicates a need for better powered, high‐quality trials. [ABSTRACT FROM AUTHOR]

Implementation of wastewater surveillance at music festivals has been limited to date. We aimed to use wastewater analysis and a self-report survey to determine the range of psychoactive substances being used during a music festival season in New South Wales, Australia. We sampled six single-day music festivals requiring a music festival license in New South Wales from March 2019 to March 2020; between 15% and 100% of portaloos (temporary, un-fixed toilet facilities) were sampled at each festival. Samples were screened for 98 psychoactive substances and/or their metabolites with results qualitatively expressed as detection frequencies for each substance at each festival and across all festivals. We compared these data with the results of surveys of self-reported drug use at four of the six festivals. Festival attendance ranged from 6200 to 14,975 people. Amphetamine, cocaine, ketamine, methylone, MDMA, MDA, alprazolam, diazepam, etizolam, oxazepam and temazepam were found in almost all samples from all festivals. Ethylone, mephedrone and methcathinone were also found in over 50% of festivals. A norfentanyl (a fentanyl metabolite) and n-ethylpentylone were found at 2/6 and 1/6 festivals. No festival survey participant reported intentionally taking cathinones. The detection frequency for cathinones was higher than expected relative to recent other data sources and this may represent adulteration or substitution. Similarly, the appearance of etizolam may be related to the use of counterfeit alprazolam. The detection of highly toxic substances such as N-ethylpentylone and norfentanyl may warrant public health alerts. If provided close to real time, wastewater analysis at festivals could be complemented with information sources such as drug checking, on-site surveys, medical presentations and intelligence from peer networks to feed into early warning systems, public health alerts and peer-based harm reduction education during the festival season. [ABSTRACT FROM AUTHOR]

Introduction: There are few contemporary data on illicit drug use at music festivals. We describe drug use patterns and prevalence of specific higher‐risk drug‐related behaviours, and their associations with festivalgoer characteristics. Methods: We approached attendees at six major music festivals in New South Wales, Australia, from November 2019 to March 2020. Participants self‐completed an anonymous survey on prior and intended drug use and associated higher‐risk behaviours; double dropping; higher‐volume ethanol alongside drug use; higher quantity 3,4‐methylenedioxymethamphetamine (MDMA); mixing stimulants; and preloading. Logistic regression and UpSet analyses were performed to identify festivalgoer characteristics and the intersection of high‐risk behaviours, respectively. Results: Of 1229 participants, 372 (30.3%) used or planned to use drugs at the festival. In multivariable analyses, men and those purchasing drugs both inside and outside the venue had greater odds of engaging in higher‐risk behaviours. Of those using MDMA, 47.9% reported double dropping. People using drugs for the first time had 3.3 (95% confidence interval 1.2–8.7) greater odds of higher‐volume ethanol alongside drug use. People reporting that police/police dog presence influenced their decision to take drugs had 2.2 (95% confidence interval 1.4–3.6) greater odds of preloading. In UpSet analysis, preloading was the most common intersection (17% of those using drugs). Discussions and Conclusions: Engagement in the five higher‐risk drug behaviours was common, particularly amongst males and those using drugs for the first time, while police/police dog presence appeared to influence higher‐risk behaviours amongst festival attendees. This information can be used to inform harm reduction advice, public health and law enforcement strategies. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to gather a range of opinions, including those of affected people (consumers, concerned others) to identify clinical research priorities for methamphetamine and emerging drugs of concern in Australia, to guide the work of the National Centre for Clinical Research on Emerging Drugs (NCCRED). Methods: A priority setting study was conducted (February–March 2019) in four phases: online stakeholder survey, thematic analysis of responses, rapid literature review, expert panel ranking of priorities against predetermined criteria. Results: Forty‐seven respondents completed the survey, including people identifying as one or more of: researcher (53%, n = 25), clinician (45%; n = 21), family/friend/caregiver of someone who uses methamphetamine/emerging drugs (15%, n = 7) and consumer of methamphetamine/emerging drugs (13%, n = 6). Expert panel, evidence‐informed top‐ranked clinical research priorities for methamphetamine were: strategies to overcome barriers to intervention uptake, pilot medication trials for adults seeking treatment, and communication strategies regarding evidence‐based treatments. For emerging drugs of concern, top‐ranked priorities were: piloting community‐located drug checking, feasibility of social media/other opportunities to alert consumers of emerging risks, GHB overdose and withdrawal management, and impacts of an early warning information system on reducing harms. Discussion and Conclusions: We demonstrate feasibility of a structured, collaborative clinical research priority setting process. Results have informed the establishment of NCCRED; using the identified priorities to guide seed funding, fellowships/scholarships and research programs. Broader uptake of this methodology by policymakers/research funders would assist to embed areas of concern identified by affected communities and other stakeholders in research prioritisation. [ABSTRACT FROM AUTHOR]

Background: Missing more than one tablet of contemporary antiretroviral therapy (ART) per month increases the risk of virological failure. Recent studies evaluating a comprehensive range of potential risk factors for suboptimal adherence are not available for high-income settings. Methods: Adults on ART with undetectable viral load (UDVL) were recruited into a national, multi-centre cohort, completing a comprehensive survey assessing demographics, socio-economic indicators, physical health, well-being, life stressors, social supports, HIV disclosure, HIV-related stigma and discrimination, healthcare access, ART regimen, adherence, side effects, costs and treatment beliefs. Baseline data were assessed, and suboptimal adherence was defined as self-reported missing ≥1 ART dose/month over the previous 3-months; associated factors were identified using bivariate and multivariate binary logistic regression. Results: We assessed 522 participants (494 [94.5%] men, mean age = 50.8 years, median duration UDVL = 3.3 years [IQR = 1.2–6.8]) at 17 sexual health, hospital, and general practice clinics across Australia. Seventy-eight participants (14.9%) reported missing ≥1 dose/month over the previous three months, which was independently associated with: being Australian-born (AOR [adjusted odds ratio] = 2.4 [95%CI = 1.2–4.9], p = 0.014), not being in a relationship (AOR = 3.3 [95%CI = 1.5–7.3], p = 0.004), reaching the “Medicare safety net” (capping annual medical/pharmaceutical costs) (AOR = 2.2 [95%CI = 1.1–4.5], p = 0.024), living in subsidised housing (AOR = 2.5 [95%CI = 1.0–6.2], p = 0.045), receiving home-care services (AOR = 4.4 [95%CI = 1.0–18.8], p = 0.046), HIV community/outreach services linkage (AOR = 2.4 [95%CI = 1.1–5.4], p = 0.033), and starting ART following self-request (AOR = 3.0 [95%CI = 1.3–7.0], p = 0.012). Conclusions: In this population, 15% reported recent suboptimal ART adherence at levels associated in prospective studies with subsequent virological failure, despite all having an undetectable viral load. Associations were with social/economic/cultural/patient engagement factors, but not ART regimen/clinical factors. These associations may help identify those at higher risk of future virological failure and guide patient education and support. [ABSTRACT FROM AUTHOR]

Introduction: Supervised injectable opioid treatment (SIOT) is an evidence-based intervention targeting opioid-dependent people for whom existing treatments have been ineffective. This project will primarily assess the feasibility and the acceptability of time-limited SIOT using injectable hydromorphone delivered in an existing Australian public opioid treatment programme, with secondary outcomes of safety, cost, changes in drug use and other health outcomes. If feasible, the goal is to scale up the intervention to be more widely available in Australia., Methods and Analysis: Between 20 and 30 participants will be offered two times per day hydromorphone to inject under direct observation, in addition to their current opioid agonist treatment (OAT), for up to 2 years. At the end of 2 years of supervised hydromorphone treatment, participants will be continued on standard OAT only. Informed consent will be obtained from all participants included in the study. This is a single-site, uncontrolled, open-label study where quantitative and qualitative interview data will be collected at baseline, 12 months and lastly at 3 months following their final hydromorphone dose. The main outcome measures are feasibility, as assessed by recruitment, retention and participation in treatment, and acceptability to participants, clinic staff and other stakeholders assessed by qualitative interviews. Secondary outcome measures of safety, as assessed by adverse events, and cost will also be assessed, as well as a range of other drug and health outcomes., Ethics and Dissemination: This study received ethical approval from the St Vincent's Hospital Human Research Ethics Committee (2019/ETH00418). This will be the first study of time-limited SIOT in the Australian setting. All results will be submitted to peer-reviewed journals, scientific conferences and local practice meetings. A preliminary report on outcomes will also be presented to local health policy makers. A consumer and community forum will also be held to feedback results to a broader audience., Trial Registration Number: ACTRN12621001729819., Competing Interests: Competing interests: JS, through his university, has worked with several pharmaceutical companies to identify new or improved treatments and his employer (King’s College London) has received grants, travel costs and/or consultancy payments. None of these is related to the FOpIT study described in this paper. NL has received funding for independent research from Indivior and Camurus for work unrelated to this project. KJS and NE have received funding from the Australian Department of Health and Aged Care, and is employed by the University of New South Wales and St Vincent’s Hospital, Sydney. WvdB has worked with several pharmaceutical companies to identify new or improved treatments and received speaker fees, travel costs and/or consultancy payments. None of these is related to the FOpIT study described in this paper., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Interventions are required that address delays in treatment-seeking and low treatment coverage among people consuming methamphetamine., Objective: We aim to determine whether a self-administered smartphone-based intervention, the "S-Check app" can increase help-seeking and motivation to change methamphetamine use, and determine factors associated with app engagement., Methods: This study is a randomized, 28-day waitlist-controlled trial. Consenting adults residing in Australia who reported using methamphetamine at least once in the last month were eligible to download the app for free from Android or iOS app stores. Those randomized to the intervention group had immediate access to the S-Check app, the control group was wait-listed for 28 days before gaining access, and then all had access until day 56. Actual help-seeking and intention to seek help were assessed by the modified Actual Help Seeking Questionnaire (mAHSQ), modified General Help Seeking Questionnaire, and motivation to change methamphetamine use by the modified readiness ruler. χ 2 comparisons of the proportion of positive responses to the mAHSQ, modified General Help Seeking Questionnaire, and modified readiness ruler were conducted between the 2 groups. Logistic regression models compared the odds of actual help-seeking, intention to seek help, and motivation to change at day 28 between the 2 groups. Secondary outcomes were the most commonly accessed features of the app, methamphetamine use, feasibility and acceptability of the app, and associations between S-Check app engagement and participant demographic and methamphetamine use characteristics., Results: In total, 560 participants downloaded the app; 259 (46.3%) completed eConsent and baseline; and 84 (32.4%) provided data on day 28. Participants in the immediate access group were more likely to seek professional help (mAHSQ) at day 28 than those in the control group (n=15, 45.5% vs n=12, 23.5%; χ 2 1 =4.42, P=.04). There was no significant difference in the odds of actual help-seeking, intention to seek help, or motivation to change methamphetamine use between the 2 groups on the primary logistic regression analyses, while in the ancillary analyses, the imputed data set showed a significant difference in the odds of seeking professional help between participants in the immediate access group compared to the waitlist control group (adjusted odds ratio 2.64, 95% CI 1.19-5.83, P=.02). For participants not seeking help at baseline, each minute in the app increased the likelihood of seeking professional help by day 28 by 8% (ratio 1.08, 95% CI 1.02-1.22, P=.04). Among the intervention group, a 10-minute increase in app engagement time was associated with a decrease in days of methamphetamine use by 0.4 days (regression coefficient [β] -0.04, P=.02)., Conclusions: The S-Check app is a feasible low-resource self-administered intervention for adults in Australia who consume methamphetamine. Study attrition was high and, while common in mobile health interventions, warrants larger studies of the S-Check app., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12619000534189; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377288&isReview=true., (©Krista J Siefried, Florence Bascombe, Brendan Clifford, Zhixin Liu, Peter Middleton, Frances Kay-Lambkin, Jack Freestone, Daniel Herman, Michael Millard, Maureen Steele, Liam Acheson, Carl Moller, Nicky Bath, Nadine Ezard. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 03.07.2024.)

Objectives: Although factors associated with alcohol use have been researched at a population level, descriptions of the alcohol and other drug (AOD) treatment-seeking population in New South Wales (NSW), Australia, are limited. This study addresses this gap by analyzing sociodemographic and health characteristics in the NSW AOD treatment-seeking population., Methods: Self-reported Australian Treatment Outcomes Profile data on substance use, health ratings, and sociodemographic factors were acquired from public AOD services (offering services from counseling to ambulatory/inpatient withdrawal management) in 6 administrative health districts from 2016 to 2019 (n = 14,287). Gaussian and multiple logistic regressions were conducted to examine associations between these factors and alcohol consumption quantity., Results: Data were analyzed for patients seeking treatment for alcohol consumption specifically (n = 5929; median age, 44 years; 65% male). Valid alcohol consumption data were available for 5460 patients, among whom the mean volume of alcohol consumed was 311 standard drinks (3110 grams of ethanol) over the past 28 days and 15 standard drinks (150 grams of ethanol) per occasion. Higher volumes were consumed by males and those with recent experiences of violence and/or injecting drug use. Caring for children younger than 5 years and having above-median health ratings were associated with lower alcohol consumption., Conclusions: This study contributes to the characterization of the NSW public AOD treatment population and identifies associations between alcohol consumption, sociodemographic factors, and health ratings among people seeking treatment for alcohol consumption. Findings point towards multilevel assessment and comprehensive interventions for people engaging in treatment for alcohol use. Future research should address barriers to treatment., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Background: High antiretroviral therapy (ART) coverage and viral suppression among people with HIV (PWH) in Australia provide a unique context to study individual cognitive trajectories, cognitive aging and factors associated with longitudinal cognitive function during chronic and stable HIV disease., Methods: Participants from the Predictors of Adherence to Antiretroviral Therapy study (n = 457, recruited between September 2013 and November 2015, median age = 52 years, and all with HIV RNA <50 copies mL) completed a cognitive assessment with CogState Computerized Battery (CCB) at baseline, Month-12, and Month-24. Demographics, psycho-social and socioeconomic factors, healthcare seeking behaviors, HIV disease characteristics and comorbidities were assessed. The CCB data were corrected for age, sex and practice effect and averaged into a global z-score (GZS). Cognitive impairment was defined with the global deficit score method (GDS>0.5). Meaningful cognitive change was statistically defined (decline or improvement versus stability, i.e., 90% CI, that is p < 0.05, 2-tailed) using a novel evidence-based change score: the linear mixed-effect regression (LMER)-based GZS change score. A separate LMER model with a top-down variable selection approach identified the independent effects of age and other demographic, HIV disease characteristics, socioeconomic and health-related factors on the demographically corrected GZS. The combined definitions of change and cross-sectional impairment enabled the identification of cognitive trajectories., Findings: At Month-12 and Month-24, 6% and 7% showed meaningful cognitive decline and 4% and 3% improved respectively. Only 1% showed sustained decline. Incident impairment due to subtle cognitive decline (i.e., below the threshold of meaningful cognitive decline) was 31% and 25% at Month-12 and Month-24, while 14% showed sustained impairment (i.e., cognitively impaired at all study visits). Older age (≥50 years) and time interaction was associated with lower demographically corrected GZS (β = -0.31, p < 0.001). Having a regular relationship, excellent English proficiency, and perceived stigma (avoidance) were associated with higher GZS (all p < 0.05). Relying on government subsidy, severe depression, and lower belief in ART necessity and higher concerns were associated with lower GZS (all p < 0.05). No HIV disease characteristics had a significant effect., Interpretations: Meaningful cognitive decline was not different from normal expectation in chronic stable HIV disease. Despite this, subtle cognitive decline, sustained cognitive impairment, and greater than normative-age cognitive aging were evident., Funding: Funding for the PAART study was provided in part by unrestricted educational grants from Gilead Sciences (www.gilead.com) (Grant Number: IN-AU-264- 0131), the Balnaves Foundation (www.balnavesfoundation.com), the Victorian Department of Health and Human Services (Australia) (www.dhs.vic.gov.au/home), Western Australia Health (www.health.wa.gov.au), the ACT Ministry of Health (Australia) (www.health.act.gov.au), and in-kind support from the Queensland Department of Health (Australia) (www.health.qld.gov.au), and NHMRC Partnership grant APP1058474 (PI: Carr, Andrew)., Competing Interests: Andrew Carr received consulting fees from Gilead and ViiV; honoraria for lectures or presentations from Gilead; and payment for participation on a Data Safety Monitoring Board or Advisory Board from Gilead, ViiV and MSD. Krista Siefried received travel support/sponsorship to attend conferences from Gilead. Bruce Brew received payment or honoraria for lectures or presentations from Jasnssen. All the other authors declare no conflicts of interest., (© 2022 The Authors.)