Aims: This review provides an up‐to‐date curated source of information on alcohol, tobacco and illicit drug use and their associated mortality and burden of disease. Limitations in the data are also discussed, including how these can be addressed in the future.Methods: Online data sources were identified through expert review. Data were obtained mainly from the World Health Organization, United Nations Office on Drugs and Crime and Institute for Health Metrics and Evaluation.Results: In 2015, the estimated prevalence among the adult population was 18.4% for heavy episodic alcohol use (in the past 30 days); 15.2% for daily tobacco smoking; and 3.8, 0.77, 0.37 and 0.35% for past‐year cannabis, amphetamine, opioid and cocaine use, respectively. European regions had the highest prevalence of heavy episodic alcohol use and daily tobacco use. The age‐standardized prevalence of alcohol dependence was 843.2 per 100 000 people; for cannabis, opioids, amphetamines and cocaine dependence it was 259.3, 220.4, 86.0 and 52.5 per 100 000 people, respectively. High‐income North America region had among the highest rates of cannabis, opioid and cocaine dependence. Attributable disability‐adjusted life‐years (DALYs) were highest for tobacco smoking (170.9 million DALYs), followed by alcohol (85.0 million) and illicit drugs (27.8 million). Substance‐attributable mortality rates were highest for tobacco smoking (110.7 deaths per 100 000 people), followed by alcohol and illicit drugs (33.0 and 6.9 deaths per 100 000 people, respectively). Attributable age‐standardized mortality rates and DALYs for alcohol and illicit drugs were highest in eastern Europe; attributable age‐standardized tobacco mortality rates and DALYs were highest in Oceania.Conclusions: In 2015 alcohol use and tobacco smoking use between them cost the human population more than a quarter of a billion disability‐adjusted life years, with illicit drugs costing further tens of millions. Europeans suffered proportionately more, but in absolute terms the mortality rate was greatest in low‐ and middle‐income countries with large populations and where the quality of data was more limited. Better standardized and rigorous methods for data collection, collation and reporting are needed to assess more accurately the geographical and temporal trends in substance use and its disease burden.

Although 20%-40% of persons with acute hepatitis C virus (HCV) infection demonstrate spontaneous clearance, the time course and factors associated with clearance remain poorly understood. We investigated the time to spontaneous clearance and predictors among participants with acute HCV using Cox proportional hazards analyses. Data for this analysis were drawn from an international collaboration of nine prospective cohorts evaluating outcomes after acute HCV infection. Among 632 participants with acute HCV, 35% were female, 82% were Caucasian, 49% had interleukin-28 (IL28)B CC genotype (rs12979860), 96% had injected drugs ever, 47% were infected with HCV genotype 1, and 7% had human immunodeficiency virus (HIV) coinfection. Twenty-eight percent were HCV antibody negative/RNA positive at the time of acute HCV detection (early acute HCV). During follow-up, spontaneous clearance occurred in 173 of 632, and at 1 year after infection, 25% (95% confidence interval [CI]: 21, 29) had cleared virus. Among those with clearance, the median time to clearance was 16.5 weeks (IQR: 10.5, 33.4), with 34%, 67%, and 83% demonstrating clearance at 3, 6, and 12 months. Adjusting for age, factors independently associated with time to spontaneous clearance included female sex (adjusted hazards ratio [AHR]: 2.16; 95% CI: 1.48, 3.18), IL28B CC genotype (versus CT/TT; AHR, 2.26; 95% CI: 1.52, 3.34), and HCV genotype 1 (versus non-genotype 1; AHR: 1.56; 95% CI: 1.06, 2.30). The effect of IL28B genotype and HCV genotype on spontaneous clearance was greater among females, compared to males. Conclusions : Female sex, favorable IL28B genotype, and HCV genotype 1 are independent predictors of spontaneous clearance. Further research is required to elucidate the observed sex-based differences in HCV control.

Despite revised guidelines that no longer exclude people who inject drugs (PWID) from treatment for hepatitis C virus (HCV) infection, many clinicians are reluctant to treat recent PWID. This study aimed to evaluate the efficacy of sofosbuvir and velpatasvir therapy in people with chronic HCV infection and recent injection drug use. In this open-label, single-arm phase 4 trial (SIMPLIFY), we recruited participants with recent injection drug use (past 6 months) and chronic HCV genotype 1-6 infection from seven countries (19 sites). Participants received oral sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks. Therapy was given in 1-week electronic blister packs to record the time and date of each dose. The primary endpoint was the proportion of patients with sustained virological response 12 weeks after completion of treatment (SVR12; defined as HCV RNA <12 IU/mL), analysed in all patients who received at least one dose. This study is registered with ClinicalTrials.gov, number NCT02336139, and follow-up is ongoing to evaluate the secondary endpoint of HCV reinfection. Between March 29, and Oct 31, 2016, we enrolled 103 participants; 29 (28%) of whom were female, nine (9%) had cirrhosis, 36 (35%) had HCV genotype 1, five (5%) had genotype 2, 60 (58%) had genotype 3, and two (2%) had genotype 4. 61 (59%) participants were receiving opioid substitution therapy during the study, 76 (74%) injected in the past month, and 27 (26%) injected at least daily in the past month. 100 (97%) of 103 participants completed treatment; two people were lost to follow-up and one person died from an overdose. There were no virological failures. 97 (94%, 95% CI 88-98) of 103 people achieved SVR12. Three participants with an end-of-treatment response did not have a SVR; two were lost to follow-up and one had reinfection. Drug use before and during treatment did not affect SVR12. Treatment-related adverse events were seen in 48 (47%) patients (one grade 3, no grade 4). Seven (7%) patients had at least one serious adverse event; only one such event (rhabdomyolysis, resolved) was possibly related to the therapy. One case of HCV reinfection was observed. HCV treatment should be offered to PWID, irrespective of ongoing drug use. Recent injection drug use should not be used as a reason to withhold reimbursement of HCV therapy. Gilead Sciences.

Background and Aims: People who have recently injected drugs are a priority population in efforts to achieve hepatitis C virus (HCV) elimination. This study estimated the prevalence and number of people with recent injecting drug use living with HCV, and the proportion of people with recent injecting drug use among all people living with HCV infection at global, regional and country‐levels.Methods: Data from a global systematic review of injecting drug use and HCV antibody prevalence among people with recent (previous year) injecting drug use were used to estimate the prevalence and number of people with recent injecting drug use living with HCV. These data were combined with a systematic review of global HCV prevalence to estimate the proportion of people with recent injecting drug use among all people living with HCV.Results: There are an estimated 6.1 million [95% uncertainty interval (UI) = 3.4–9.2] people with recent injecting drug use aged 15–64 years living with HCV globally (39.2% viraemic prevalence; UI = 31.6–47.0), with the greatest numbers in East and Southeast Asia (1.5 million, UI = 1.0–2.1), eastern Europe (1.5 million, UI = 0.7–2.4) and North America (1.0 million, UI = 0.4–1.7). People with recent injecting drug use comprise an estimated 8.5% (UI = 4.6–13.1) of all HCV infections globally, with the greatest proportions in North America (30.5%, UI = 11.7–56.7), Latin America (22.0%, UI = 15.3–30.4) and eastern Europe (17.9%, UI = 8.2–30.9).Conclusions: Although, globally, 39.2% of people with recent injecting drug use are living with hepatitis C virus (HCV) and 8.5% of all HCV infections occur globally among people with recent injecting drug use, there is wide variation among countries and regions.