Bradley Mathers

Global epidemiology of injecting drug use and HIV among people who inject drugs: a systematic review

BACKGROUND Injecting drug use is an increasingly important cause of HIV transmission in most countries worldwide. Our aim was to determine the prevalence of injecting drug use among individuals aged 15-64 years, and of HIV among people who inject drugs. METHODS We did a systematic search of peer-reviewed (Medline, EmBase, and PubMed/BioMed Central), internet, and grey literature databases; and data requests were made to UN agencies and international experts. 11 022 documents were reviewed, graded, and catalogued by the Reference Group to the UN on HIV and Injecting Drug Use. FINDINGS Injecting drug use was identified in 148 countries; data for the extent of injecting drug use was absent for many countries in Africa, the Middle East, and Latin America. The presence of HIV infection among injectors had been reported in 120 of these countries. Prevalence estimates of injecting drug use could be ascertained for 61 countries, containing 77% of the worlds total population aged 15-64 years. Extrapolated estimates suggest that 15.9 million (range 11.0-21.2 million) people might inject drugs worldwide; the largest numbers of injectors were found in China, the USA, and Russia, where mid-estimates of HIV prevalence among injectors were 12%, 16%, and 37%, respectively. HIV prevalence among injecting drug users was 20-40% in five countries and over 40% in nine. We estimate that, worldwide, about 3.0 million (range 0.8-6.6 million) people who inject drugs might be HIV positive. INTERPRETATION The number of countries in which the injection of drugs has been reported has increased over the last decade. The high prevalence of HIV among many populations of injecting drug users represents a substantial global health challenge. However, existing data are far from adequate, in both quality and quantity, particularly in view of the increasing importance of injecting drug use as a mode of HIV transmission in many regions.

Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews

BACKGROUND Injecting drug use is an important risk factor for transmission of viral hepatitis, but detailed, transparent estimates of the scale of the issue do not exist. We estimated national, regional, and global prevalence and population size for hepatitis C virus (HCV) and hepatitis B virus (HBV) in injecting drug users (IDUs). METHODS We systematically searched for data for HBV and HCV in IDUs in peer-reviewed databases (Medline, Embase, and PsycINFO), grey literature, conference abstracts, and online resources, and made a widely distributed call for additional data. From 4386 peer-reviewed and 1019 grey literature sources, we reviewed 1125 sources in full. We extracted studies into a customised database and graded them according to their methods. We included serological reports of HCV antibodies (anti-HCV), HBV antibodies (anti-HBc), or HBV surface antigen (HBsAg) in studies of IDUs with more than 40 participants (<100% HIV-positive) and sampling frames that did not exclude participants on the basis of age or sex. With endorsed decision rules, we calculated prevalence estimates with anti-HCV and anti-HBc as proxies for exposure and HBsAg as proxy for current infection. We combined these estimates with IDU population sizes to calculate the number of IDUs with positive HBV or HCV statuses. FINDINGS We located eligible reports with data for prevalence of anti-HCV in IDUs for 77 countries; midpoint prevalence estimates suggested 60-80% of IDUs had anti-HCV in 25 countries and more than 80% of IDUs did so in 12 countries. About 10.0 million (range 6.0-15.2) IDUs worldwide might be anti-HCV positive. China (1.6 million), USA (1.5 million), and Russia (1.3 million) had the largest such populations. We identified eligible HBsAg reports for 59 countries, with midpoint prevalence estimates of 5-10% in 21 countries and more than 10% in ten countries. Worldwide, we estimate 6.4 million IDUs are anti-HBc positive (2.3-9.7 million), and 1.2 million (0.3-2.7 million) are HBsAg positive. INTERPRETATION More IDUs have anti-HCV than HIV infection, and viral hepatitis poses a key challenge to public health. Variation in the coverage and quality of existing research creates uncertainty around estimates. Improved and more complete data and reporting are needed to estimate the scale of the issue, which will inform efforts to prevent and treat HCV and HBV in IDUs. FUNDING WHO and US National Institutes of Health (NIDA R01 DA018609).

HIV prevention, treatment, and care services for people who inject drugs: a systematic review of global, regional, and national coverage

BACKGROUND Previous reviews have examined the existence of HIV prevention, treatment, and care services for injecting drug users (IDUs) worldwide, but they did not quantify the scale of coverage. We undertook a systematic review to estimate national, regional, and global coverage of HIV services in IDUs. METHODS We did a systematic search of peer-reviewed (Medline, BioMed Central), internet, and grey-literature databases for data published in 2004 or later. A multistage process of data requests and verification was undertaken, involving UN agencies and national experts. National data were obtained for the extent of provision of the following core interventions for IDUs: needle and syringe programmes (NSPs), opioid substitution therapy (OST) and other drug treatment, HIV testing and counselling, antiretroviral therapy (ART), and condom programmes. We calculated national, regional, and global coverage of NSPs, OST, and ART on the basis of available estimates of IDU population sizes. FINDINGS By 2009, NSPs had been implemented in 82 countries and OST in 70 countries; both interventions were available in 66 countries. Regional and national coverage varied substantially. Australasia (202 needle-syringes per IDU per year) had by far the greatest rate of needle-syringe distribution; Latin America and the Caribbean (0.3 needle-syringes per IDU per year), Middle East and north Africa (0.5 needle-syringes per IDU per year), and sub-Saharan Africa (0.1 needle-syringes per IDU per year) had the lowest rates. OST coverage varied from less than or equal to one recipient per 100 IDUs in central Asia, Latin America, and sub-Saharan Africa, to very high levels in western Europe (61 recipients per 100 IDUs). The number of IDUs receiving ART varied from less than one per 100 HIV-positive IDUs (Chile, Kenya, Pakistan, Russia, and Uzbekistan) to more than 100 per 100 HIV-positive IDUs in six European countries. Worldwide, an estimated two needle-syringes (range 1-4) were distributed per IDU per month, there were eight recipients (6-12) of OST per 100 IDUs, and four IDUs (range 2-18) received ART per 100 HIV-positive IDUs. INTERPRETATION Worldwide coverage of HIV prevention, treatment, and care services in IDU populations is very low. There is an urgent need to improve coverage of these services in this at-risk population. FUNDING UN Office on Drugs and Crime; Australian National Drug and Alcohol Research Centre, University of New South Wales; and Australian National Health and Medical Research Council.

Mortality among regular or dependent users of heroin and other opioids: a systematic review and meta‐analysis of cohort studies

AIMS To review the literature on mortality among dependent or regular users of opioids across regions, according to specific causes, and related to a number of demographic and clinical variables. METHODS Multiple search strategies included searches of Medline, EMBASE and PsycINFO, consistent with the methodology recommended by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group; grey literature searches; and contact of experts for any additional unpublished data from studies meeting inclusion criteria. Random-effects meta-analyses were conducted for crude mortality rates (CMRs) and standardized mortality ratios (SMRs), with stratified analyses where possible. Meta-regressions examined potentially important sources of heterogeneity across studies. RESULTS Fifty-eight prospective studies reported mortality rates from opioid-dependent samples. Very high heterogeneity across studies was observed; pooled all-cause CMR was 2.09 per 100 person-years (PY; 95% CI; 1.93, 2.26), and the pooled SMR was 14.66 (95% CI: 12.82, 16.50). Males had higher CMRs and lower SMRs than females. Out-of-treatment periods had higher mortality risk than in-treatment periods (pooled RR 2.38 (CI: 1.79, 3.17)). Causes of death varied across studies, but overdose was the most common cause. Multivariable regressions found the following predictors of mortality rates: country of origin; the proportion of sample injecting; the extent to which populations were recruited from an entire country (versus subnational); and year of publication. CONCLUSIONS Mortality among opioid-dependent users varies across countries and populations. Treatment is clearly protective against mortality even in non-randomized observational studies. Study characteristics predict mortality levels; these should be taken into account in future studies.

Prevention of HIV infection for people who inject drugs: why individual, structural, and combination approaches are needed

HIV can spread rapidly between people who inject drugs (through injections and sexual transmission), and potentially the virus can pass to the wider community (by sexual transmission). Here, we summarise evidence on the effectiveness of individual-level approaches to prevention of HIV infection; review global and regional coverage of opioid substitution treatment, needle and syringe programmes, and antiretroviral treatment; model the effect of increased coverage and a combination of these three approaches on HIV transmission and prevalence in injecting drug users; and discuss evidence for structural-level interventions. Each intervention alone will achieve modest reductions in HIV transmission, and prevention of HIV transmission necessitates high-coverage and combined approaches. Social and structural changes are potentially beneficial components in a combined-intervention strategy, especially when scale-up is difficult or reductions in HIV transmission and injection risk are difficult to achieve. Although further evidence is needed on how to optimise combinations of interventions in different settings and epidemics, we know enough now about which actions are effective: the challenge is to deliver these well and to scale.

Mortality among people who inject drugs: a systematic review and meta-analysis

OBJECTIVE To systematically review cohort studies of mortality among people who inject drugs, examine mortality rates and causes of death in this group, and identify participant- and study-level variables associated with a higher risk of death. METHODS Tailored search strings were used to search EMBASE, Medline and PsycINFO. The grey literature was identified through online grey literature databases. Experts were consulted to obtain additional studies and data. Random effects meta-analyses were performed to estimate pooled crude mortality rates (CMRs) and standardized mortality ratios (SMRs). FINDINGS Sixty-seven cohorts of people who inject drugs were identified, 14 of them from low- and middle-income countries. The pooled CMR was 2.35 deaths per 100 person-years (95% confidence interval, CI: 2.12-2.58). SMRs were reported for 32 cohorts; the pooled SMR was 14.68 (95% CI: 13.01-16.35). Comparison of CMRs and the calculation of CMR ratios revealed mortality to be higher in low- and middle-income country cohorts, males and people who injected drugs that were positive for human immunodeficiency virus (HIV). It was also higher during off-treatment periods. Drug overdose and acquired immunodeficiency syndrome (AIDS) were the primary causes of death across cohorts. CONCLUSION Compared with the general population, people who inject drugs have an elevated risk of death, although mortality rates vary across different settings. Any comprehensive approach to improving health outcomes in this group must include efforts to reduce HIV infection as well as other causes of death, particularly drug overdose.

Meth/amphetamine use and associated HIV: Implications for global policy and public health

Amphetamine type stimulants (ATS) have become the focus of increasing attention worldwide. There are understandable concerns over potential harms including the transmission of HIV. However, there have been no previous global reviews of the extent to which these drugs are injected or levels of HIV among users. A comprehensive search of the international peer-reviewed and grey literature was undertaken. Multiple electronic databases were searched and documents and datasets were provided by UN agencies and key experts from around the world in response to requests for information on the epidemiology of use. Amphetamine or methamphetamine (meth/amphetamine, M/A) use was documented in 110 countries, and injection in 60 of those. Use may be more prevalent in East and South East Asia, North America, South Africa, New Zealand, Australia and a number of European countries. In countries where the crystalline form is available, evidence suggests users are more likely to smoke or inject the drug; in such countries, higher levels of dependence may be occurring. Equivocal evidence exists as to whether people who inject M/A are at differing risk of HIV infection than other drug injectors; few countries document HIV prevalence/incidence among M/A injectors. High risk sexual behaviour among M/A users may contribute to increased risk of HIV infection, but available evidence is not sufficient to determine if the association is causal. A range of possible responses to M/A use and harm are discussed, ranging from supply and precursor control, to demand and harm reduction. Evidence suggests that complex issues surround M/A, requiring novel and sophisticated approaches, which have not yet been met with sufficient investment of time or resources to address them. Significant levels of M/A in many countries require a response to reduce harms that in many cases remain poorly understood. More active models of engagement with M/A users and provision of services that meet their specific needs are required.

Estimating levels of HIV testing, HIV prevention coverage, HIV knowledge, and condom use among men who have sex with men (MSM) in low-income and middle-income countries.

Background:HIV prevalence data suggest that men who have sex with men (MSM) in low-income and middle-income countries (LMIC) are at increased risk of HIV. The aim of this article is to present global estimates on key HIV prevention needs and responses among MSM in LMIC. Methods:Data on HIV testing, HIV prevention coverage, HIV knowledge and condom use among MSM were derived from UNGASS country progress reports submitted in 2008. Eligible country estimates were used to calculate global and regional estimates, weighted for the size of MSM populations. Results:Of 147 LMIC, 45% reported at least 1 indicator that reflects the HIV prevention needs and responses in MSM. Global weighted estimates indicate that on average 31% of MSM in LMIC were tested for HIV; 33% were reached by HIV prevention programs; 44% had correct HIV knowledge; and 54% used condoms the last time they had anal sex with a man. Conclusions:The 2008 UNGASS country reports represent the largest harmonized data set to date of HIV prevention needs and responses among MSM in LMIC. Although reporting is incomplete and does not always conform to requirements, findings confirm that, in many LMIC, HIV prevention responses in MSM need substantial strengthening.

The global epidemiology and burden of opioid dependence: results from the global burden of disease 2010 study

AIMS To estimate the prevalence and burden of disease attributable to opioid dependence globally, regionally and at country level. METHODS Multiple search strategies: (i) peer-reviewed literature searches; (ii) systematic searches of online databases; (iii) internet searches; (iv) consultation and feedback from experts. Culling and data extraction followed protocols. DisMod-MR, the latest version of the generic disease modelling system, a Bayesian meta-regression tool, imputed prevalence by age, year and sex for 187 countries and 21 regions. Disability weight for opioid dependence was estimated through population surveys and multiplied by prevalence data to calculate the years of life lived with disability (YLDs). Opioid dependence premature mortality was computed as years of life lost (YLLs) and summed with YLDs to calculate disability-adjusted life years (DALYs). RESULTS There were 15.5 million opioid-dependent people globally in 2010 [0.22%, 95% uncertainty interval (UI) = 0.20-0.25%]. Age-standardized prevalence was higher in males (0.30%, 95% UI = 0.27-0.35%) than females (0.14%, 95% UI = 0.12-0.16%), and peaked at 25-29 years. Prevalence was higher than the global pooled prevalence in Australasia (0.46%, 95% UI = 0.41-0.53%), western Europe (0.35%, 95% UI = 0.32-0.39) and North America (0.30%, 95% UI = 0.25-0.36). Opioid dependence was estimated to account for 9.2 million DALYs globally (0.37% of global DALYs) in 2010, a 73% increase on DALYs estimated in 1990. Regions with the highest opioid dependence DALY rates were North America (292.1 per 100,000), eastern Europe (288.4 per 100,000), Australasia (278.6 per 100,000) and southern sub-Saharan Africa (263.5 per 100,000). The contribution of YLLs to opioid dependence burden was particularly high in North America, eastern Europe and southern sub-Saharan Africa. CONCLUSION Opioid dependence is a substantial contributor to the global disease burden; its contribution to premature mortality (relative to prevalence) varies geographically, with North America, eastern Europe and southern sub-Saharan Africa most strongly affected.

Transitions from Injection-Drug-Use-Concentrated to Self-Sustaining Heterosexual HIV Epidemics: Patterns in the International Data

Background Injecting drug use continues to be a primary driver of HIV epidemics in many parts of the world. Many people who inject drugs (PWID) are sexually active, so it is possible that high-seroprevalence HIV epidemics among PWID may initiate self-sustaining heterosexual transmission epidemics. Methods Fourteen countries that had experienced high seroprevalence (<20%) HIV epidemics among PWID and had reliable data for injection drug use (IDU) and heterosexual cases of HIV or AIDS were identified. Graphs of newly reported HIV or AIDS cases among PWID and heterosexuals were constructed to identify temporal relationships between the two types of epidemics. The year in which newly reported cases among heterosexuals surpassed newly reported cases among PWID, aspects of the epidemic curves, and epidemic case histories were analyzed to assess whether it was “plausible” or “highly unlikely” that the HIV epidemic among PWID might have initiated the heterosexual epidemic in each country. Results Transitions have occurred in 11 of the 14 countries. Two types of temporal relationships between IDU and heterosexual HIV epidemics were identified, rapid high incidence transitions vs. delayed, low incidence transitions. In six countries it appears “plausible” that the IDU epidemic initiated a heterosexual epidemic, and in five countries it appears “highly unlikely” that the IDU epidemic initiated a heterosexual epidemic. A rapid decline in incidence among PWID after the peak year of new cases and national income were the best predictors of the “highly unlikely” initiation of a heterosexual epidemic. Discussion Transitions from IDU concentrated epidemics to heterosexual epidemics are common in countries with high seroprevalence among PWID though there are distinct types of transitions. Interventions to immediately reduce HIV incidence among PWID may reduce the likelihood that an IDU epidemic may initiate a heterosexual epidemic.