Global, regional, and country-level coverage of testing and treatment for HIV and hepatitis C infection among people who inject drugs: a systematic review.

BACKGROUND: People who inject drugs are disproportionately affected by HIV and hepatitis C virus (HCV) infections, while there is little global data on HIV and HCV testing and treatment coverage of this population. We conducted a systematic review to evaluate country-level, regional, and global coverage of HIV and HCV testing and treatment among people who inject drugs. METHODS: We did a systematic review, and searched bibliographic databases (MEDLINE, Embase, and PsycINFO) and grey literature for studies published between Jan 1, 2017, and April 30, 2022, that evaluated the proportion of people who inject drugs who received testing or treatment for HIV or HCV. For each country, we estimated the proportion of people who inject drugs tested for HIV antibodies in the past 12 months (recent), people who inject drugs ever tested for HCV antibodies and HCV RNA, people who inject drugs with HIV currently receiving antiretroviral therapy, and people who inject drugs with HCV ever receiving HCV antiviral treatment. Regional and global estimates, weighted by the population size of people who inject drugs, were generated where sufficient data were available. This study is registered with PROSPERO (CRD42020173974). FINDINGS: 512 documents reported data eligible for analyses, including 337 peer-reviewed articles, 27 conference abstracts or presentations, and 148 documents from grey literature or supplementary searches. Data of recent HIV antibody testing were available for 67 countries and ever having had HCV antibody testing were available for 49 countries. Globally, an estimated 48·8% of people who inject drugs were recently tested for HIV antibodies (95% uncertainty interval [UI] 43·3-54·2%; range 0·9-86·0%), and 47·1% had ever been tested for HCV antibodies (95% UI 43·4-51·0%; range 0·0-93·3%). HCV RNA testing data were available from three countries. Coverage of HIV antibody testing was high (>75%) in four countries and for HCV antibody testing in 15 countries. The estimated uptake of current HIV treatment (18 countries) ranged from 2·6% to 81·9%, and the estimated uptake of ever having HCV treatment (23 countries) ranged from 1·8% to 88·6% across countries. Uptake of HIV treatment was high in two countries, and of HCV treatment in one country. INTERPRETATION: HIV and HCV testing and treatment uptake among people who inject drugs was highly variable, and suboptimal in most countries. Strategies to improve access to HIV and HCV care among people who inject drugs and the availability of public health surveillance are urgently required. FUNDING: Australian National Health and Medical Research Council and UK National Institute for Health and Care Research Health Protection Research Unit in Behavioural Science and Evaluation.

Epidemiology of injecting drug use, prevalence of injecting-related harm, and exposure to behavioural and environmental risks among people who inject drugs: a systematic review.

BACKGROUND: People who inject drugs are exposed to various and changing risk environments and are at risk of multiple harms related to injecting drug use (IDU). We aimed to undertake a global systematic review of the prevalence of IDU, key IDU-related harms (including HIV, hepatitis C virus [HCV], and hepatitis B virus [HBV] infection and overdose), and key sociodemographic characteristics and risk exposures for people who inject drugs. METHODS: We systematically searched for data published between Jan 1, 2017, and March 31, 2022, in databases of peer-reviewed literature (MEDLINE, Embase, and PsycINFO) and grey literature as well as various agency or organisational websites, and disseminated data requests to international experts and agencies. We searched for data on the prevalence, characteristics, and risks of people who inject drugs, including gender, age, sexuality, drug-use patterns, HIV, HCV, and HBV infections, non-fatal overdose, depression, anxiety, and injecting-related disease. Additional data were extracted from studies identified in our previous review. Meta-analyses were used to pool the data where multiple estimates were available for a country. We present country, regional, and global estimates for each variable examined. FINDINGS: We screened 40 427 reports published between 2017 and 2022, and the 871 eligible reports identified were added to the 1147 documents from the previous review. Evidence of IDU was documented in 190 of 207 countries and territories, and 14·8 million people (95% uncertainty interval [UI] 10·0-21·7) aged 15-64 years globally were estimated to inject drugs. Existing evidence suggests that there might be 2·8 million (95% UI 2·4-3·2) women and 12·1 million (95% UI 11·0-13·3) men who inject drugs globally, and that 0·4% (95% CI 0·3-1·3) of people who inject drugs identify as transgender. The amount of available data on key health and social risks among people who inject drugs varied widely across countries and regions. We estimated that 24·8% (95% CI 19·5-31·6) of people who inject drugs globally had experienced recent homelessness or unstable housing, 58·4% (95% CI 52·0-64·8) had a lifetime history of incarceration, and 14·9% (95% CI 8·1-24·3) had recently engaged in sex work, with substantial geographical variation. Injecting and sexual risk behaviour varied considerably geographically, as did risks of harms. Globally, we estimated that 15·2% (95% CI 10·3-20·9) of people who inject drugs are living with HIV, 38·8% (95% CI 31·4-46·9) have current HCV infection, 18·5% (95% CI 13·9-24·1) have recently overdosed, and 31·7% (95% CI 23·6-40·5) have had a recent skin or soft tissue infection. INTERPRETATION: IDU is being identified in a growing number of countries and territories that comprise more than 99% of the global population. IDU-related health harms are common, and people who inject drugs continue to be exposed to multiple adverse risk environments. However, quantification of many of these exposure and harms is inadequate and must be improved to allow for better targeting of harm-reduction interventions for these risks. FUNDING: Australian National Health and Medical Research Council.

Association between opioid agonist therapy use and HIV testing uptake among people who have recently injected drugs: a systematic review and meta-analysis.

BACKGROUND AND AIM: Globally, nearly one in five people who inject drugs (PWID) are living with HIV, and the rate of new HIV infections in PWID is increasing in some settings. Early diagnosis is crucial for effective HIV control. We reviewed the evidence on the association between opioid agonist therapy (OAT) and HIV testing uptake among PWID. METHODS: We conducted a systematic review searching MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and PsycINFO for studies published from January 2000 to March 2019. Reference lists and conference proceedings were hand-searched. Observational and intervention studies were eligible for inclusion. Risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. Meta-analyses were conducted using random-effects models. RESULTS: Of 13 373 records identified, 11 studies from Australia, Europe, Malaysia and the United States were included. All studies had at least a serious risk of bias, largely due to confounding and selection bias, making it difficult to draw causal conclusions from the evidence. Ten studies provided data on the association between current OAT use and recent HIV testing. Six showed a positive association, while four provided little evidence of an association: pooled odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.28-2.27. Looking at having ever been on OAT and having ever been HIV tested, seven studies showed a positive association and three showed either weak or no evidence of an association: pooled OR = 3.82, 95% CI = 2.96-4.95. CONCLUSIONS: Opioid agonist therapy may increase uptake of HIV testing among people who inject drugs, providing further evidence that opioid agonist therapy improves the HIV treatment care cascade.

All-Cause and Overdose Mortality Risk Among People Prescribed Opioids: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate all-cause and overdose crude mortality rates and standardized mortality ratios among people prescribed opioids for chronic noncancer pain and risk of overdose death in this population relative to people with similar clinical profiles but not prescribed opioids. DESIGN: Systematic review and meta-analysis. METHODS: Medline, Embase, and PsycINFO were searched in February 2018 and October 2019 for articles published beginning 2009. Due to limitations in published studies, we revised our inclusion criteria to include cohort studies of people prescribed opioids, excluding those studies where people were explicitly prescribed opioids for the treatment of opioid use disorder or acute cancer or palliative pain. We estimated pooled all-cause and overdose crude mortality rates using random effects meta-analysis models. No studies reported standardized mortality ratios or relative risks. RESULTS: We included 13 cohorts with 6,029,810 participants. The pooled all-cause crude mortality rate, based on 10 cohorts, was 28.8 per 1000 person-years (95% CI = 17.9-46.4), with substantial heterogeneity (I2 = 99.9%). The pooled overdose crude mortality rate, based on six cohorts, was 1.1 per 1000 person-years (95% CI = 0.4-3.4), with substantial heterogeneity (I2 = 99.5%), but indications for opioid prescribing and opioid exposure were poorly ascertained. We were unable to estimate mortality in this population relative to clinically similar populations not prescribed opioids. CONCLUSIONS: Methodological limitations in the identified literature complicate efforts to determine the overdose mortality risk of people prescribed opioids. There is a need for large-scale clinical trials to assess adverse outcomes in opioid prescribing, especially for chronic noncancer pain.

Integrating HIV pre-exposure prophylaxis and harm reduction among men who have sex with men and transgender women to address intersecting harms associated with stimulant use: a modelling study.

INTRODUCTION: Among men who have sex with men (MSM) and transgender women (TW), stimulant use is high and has been associated with an increased risk of HIV infection, suicide and cardiovascular disease (CVD) mortality. We used epidemic modelling to investigate these intersecting health harms among MSM/TW in Lima, Peru and assess whether they could be mitigated by prioritizing HIV pre-exposure prophylaxis (PrEP) and harm reduction interventions among MSM/TW who use stimulants. METHODS: We adapted a dynamic model of HIV transmission among MSM/TW in Lima to incorporate stimulant use and increased HIV risk, suicide and CVD mortality. Among 6% to 24% of MSM/TW using stimulants (mostly cocaine), we modelled an increased risk of unprotected anal sex (RR = 1.35 [95%CI: 1.17 to 1.57]) obtained from local data, and increased risk of suicide (SMR = 6.26 [95%CI: 2.84 to 13.80]) and CVD (SMR = 1.83 [95%CI: 0.39 to 8.57]) mortality associated with cocaine use based on a global systematic review. We estimated the proportion of health harms occurring among MSM/TW who use stimulants in the next year (01-2020/01-2021). We also investigated the 10-year impact (01-2020/01-2030) of: (1) PrEP prioritization for stimulant-using MSM/TW compared to random allocation, and (2) integrating PrEP with a theoretical intervention halving stimulant-associated risk. RESULTS: MSM/TW in Lima will experience high HIV incidence, suicide mortality and CVD mortality (1.6/100 py, and 0.018/100 py, 0.13/100 py respectively) in 2020. Despite stimulant using MSM/TW comprising an estimated 9.5% (95%CI: 7.8 to 11.5) of all MSM/TW, in the next year, 11% 95%CI (i.e. 2.5% to 97.5% percentile) 10% to 13%) of new HIV infections, 39% (95%CI: 18% to 60%) of suicides and 15% (95%CI: 3% to 44%) of CVD deaths could occur among this group. Scaling up PrEP among all stimulant using MSM/TW could prevent 19% (95%CI: 11% to 31%) more HIV infections over 10 years compared to random allocation. Integrating PrEP and an intervention to halve stimulant-associated risks could reduce new HIV infections by 20% (95%CI: 10% to 37%), suicide deaths by 14% (95%CI: 5% to 27%) and CVD deaths by 3% (95%CI: 0% to 16%) over a decade. CONCLUSIONS: MSM/TW who use stimulants experience a disproportionate burden of health harms. Prioritizing PrEP based on stimulant use, in addition to sexual behaviour/gender identity criteria, could increase its impact. Integrated substance use, harm reduction, mental health and HIV care among MSM/TW is needed.

Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis.

BACKGROUND: Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders. METHODS: For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018. We also searched for unpublished or ongoing studies on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry. We considered all studies examining any type and formulation of a medicinal cannabinoid in adults (≥18 years) for treating depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis, either as the primary condition or secondary to other medical conditions. We placed no restrictions on language, publication status, or study type (ie, both experimental and observational study designs were included). Primary outcomes were remission from and changes in symptoms of these mental disorders. The safety of medicinal cannabinoids for these mental disorders was also examined. Evidence from randomised controlled trials was synthesised as odds ratios (ORs) for disorder remission, adverse events, and withdrawals and as standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977). FINDINGS: 83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD -0·25 [95% CI -0·49 to -0·01]; seven studies; n=252), although the evidence GRADE was very low. Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD 0·36 [95% CI 0·10 to 0·62]; n=24). Pharmaceutical THC (with or without CBD) did not significantly affect any other primary outcomes for the mental disorders examined but did increase the number of people who had adverse events (OR 1·99 [95% CI 1·20 to 3·29]; ten studies; n=1495) and withdrawals due to adverse events (2·78 [1·59 to 4·86]; 11 studies; n=1621) compared with placebo across all mental disorders examined. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis. INTERPRETATION: There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework. Further high-quality studies directly examining the effect of cannabinoids on treating mental disorders are needed. FUNDING: Therapeutic Goods Administration, Australia; Commonwealth Department of Health, Australia; Australian National Health and Medical Research Council; and US National Institutes of Health.