Bradley M Mathers - University of New South Wales

Bradley M Mathers
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Name
Bradley M Mathers
Affiliation
University of New South Wales
Country
Australia

Publications Authored By Bradley M Mathers

Describe modifications to the latest version of the Joint United Nations Programme on AIDS (UNAIDS) Estimation and Projection Package component of Spectrum (EPP 2013) to improve prevalence fitting and incidence trend estimation in national epidemics and global estimates of HIV burden.
Key changes made under the guidance of the UNAIDS Reference Group on Estimates, Modelling and Projections include: availability of a range of incidence calculation models and guidance for selecting a model; a shift to reporting the Bayesian median instead of the maximum likelihood estimate; procedures for comparison and validation against reported HIV and AIDS data; incorporation of national surveys as an integral part of the fitting and calibration procedure, allowing survey trends to inform the fit; improved antenatal clinic calibration procedures in countries without surveys; adjustment of national antiretroviral therapy reports used in the fitting to include only those aged 15-49 years; better estimates of mortality among people who inject drugs; and enhancements to speed fitting.
The revised models in EPP 2013 allow closer fits to observed prevalence trend data and reflect improving understanding of HIV epidemics and associated data.Read More


Spectrum and EPP continue to adapt to make better use of the existing data sources, incorporate new sources of information in their fitting and validation procedures, and correct for quantifiable biases in inputs as they are identified and understood. These adaptations provide countries with better calibrated estimates of incidence and prevalence, which increase epidemic understanding and provide a solid base for program and policy planning.

To systematically review and analyse data from cohorts of people who inject drugs (PWID) to improve existing estimates of non-AIDS mortality used to calculate mortality among PWID in the Spectrum Estimates and Projection Package.
Systematic review and meta-analysis.
We conducted an update of an earlier systematic review of mortality among PWID, searching specifically for studies providing data on non-AIDS-related deaths.Read More

Random-effects meta-analyses were performed to derive pooled estimates of non-AIDS crude mortality rates across cohorts disaggregated by sex, HIV status and periods in and out of opioid substitution therapy (OST). Within each cohort, ratios of non-AIDS CMRs were calculated and then pooled across studies for the following paired sub-groups: HIV-negative versus HIV-positive PWID; male versus female PWID; periods in OST versus out of OST. For each analysis, pooled estimates by country income group and by geographic region were also calculated.
Thirty-seven eligible studies from high-income countries and five from low and middle-income countries were found. Non-AIDS mortality was significantly higher in low and middle-income countries [2.74 per 100 person-years; 95% confidence interval (CI) 1.76-3.72] than in high-income countries (1.56 per 100 person-years; 95% CI 1.38-1.74). Non-AIDS CMRs were 1.34 times greater among men than women (95% CI 1.14-1.57; N = 19 studies); 1.50 times greater among HIV-positive than HIV-negative PWID (95% CI 1.15, 1.96; N = 16 studies); and more than three times greater during periods out of OST than for periods on OST (N = 7 studies).
A comprehensive response to injecting drug must include efforts to reduce the high levels of non-AIDS mortality among PWID. Due to limitations of currently available data, including substantial heterogeneity between studies, estimates of non-AIDS mortality specific to geographic regions, country income level, or the availability of OST should be interpreted with caution.

In 2010 the international HIV/AIDS community called on countries to take action to prevent HIV transmission among people who inject drugs (PWID). To set a baseline we proposed an "accountability matrix", focusing upon six countries accounting for half of the global population of PWID: China, Malaysia, Russia, Ukraine, Vietnam and the USA. Two years on, we review progress.Read More


We searched peer-reviewed literature, conducted online searches, and contacted experts for 'grey' literature. We limited searches to documents published since December 2009 and used decision rules endorsed in earlier reviews.
Policy shifts are increasing coverage of key interventions for PWID in China, Malaysia, Vietnam and Ukraine. Increases in PWID receiving antiretroviral treatment (ART) and opioid substitution treatment (OST) in both Vietnam and China, and a shift in Malaysia from a punitive law enforcement approach to evidence-based treatment are promising developments. The USA and Russia have had no advances on PWID access to needle and syringe programmes (NSP), OST or ART. There have also been policy setbacks in these countries, with Russia reaffirming its stance against OST and closing down access to information on methadone, and the USA reinstituting its Congressional ban on Federal funding for NSPs.
Prevention of HIV infection and access to HIV treatment for PWID is possible. Whether countries with concentrated epidemics among PWID will meet goals of achieving universal access and eliminating new HIV infections remains unknown. As long as law enforcement responses counter public health responses, health-seeking behaviour and health service delivery will be limited.

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.
Tailored search strings were used to search EMBASE, Medline and PsycINFO. The grey literature was identified through online grey literature databases.Read More

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).
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.
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.

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.
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.Read More

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.
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.
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.

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).
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.Read More

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.
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.
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.
WHO and US National Institutes of Health (NIDA R01 DA018609).

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.
We did a systematic search of peer-reviewed (Medline, BioMed Central), internet, and grey-literature databases for data published in 2004 or later.Read More

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.
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.
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.
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.

The 2001 Declaration of Commitment from the United Nations General Assembly Special Session on HIV/AIDS (UNGASS) set the prevention of HIV infection among injecting drug users (IDUs) as an important priority in the global fight against HIV/AIDS. This article examines data gathered to monitor the fulfillment of this commitment in low-income and middle-income countries (LMICs) where resources to develop an effective response to HIV are limited and where injecting drug use is reported to occur in 99 (of 147) countries, home to 75% of the estimated 15.9 million global IDU population.Read More


Data relating to injecting drug use submitted by LMICs to the Joint United Nations Programme on HIV/AIDS (UNAIDS) in the 2008 reporting round for monitoring the Declaration of Commitment on HIV/AIDS were reviewed. The quality of the data reported was assessed and country data were aggregated and compared to determine progress in HIV prevention efforts. For each indicator, the mean value weighted for the size of each country's IDU population was determined; regional estimates were also made.
Reporting was inconsistent between countries. Forty percent of LMIC (40/99), where injecting occurs, reported data for 1 or more of the 5 indicators pertinent to HIV prevention among IDUs. Many of the data reported were excluded from this analysis because the indicators used by countries were not consistent with those defined by UNAIDS Monitoring and Evaluation Reference Group and could not be compared. Data from 32 of 99 countries met our inclusion criteria. These 32 countries account for approximately two-thirds (68%) of the total estimated IDU population in all LMICs.The IDU population weighted means are as follows: 36% of IDUs tested for HIV in the last year; 26% of IDUs reached with HIV prevention programs in the last year; 45% of IDUs with correct HIV prevention knowledge; 37% of IDUs used a condom at last sexual intercourse; and 63% of IDUs used a clean syringe at last injection. Marked variance was observed in the data reported between different regions.
Data from the 2008 United Nations General Assembly Special Session reporting round provide a baseline against which future progress might be measured. The data indicate a wide variation in HIV service coverage for IDUs and a wide divergence in HIV knowledge and risk behaviors among IDUs in different countries. Countries should be encouraged and assisted in monitoring and reporting on HIV prevention for IDUs.

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.
Data on HIV testing, HIV prevention coverage, HIV knowledge and condom use among MSM were derived from UNGASS country progress reports submitted in 2008.Read More

Eligible country estimates were used to calculate global and regional estimates, weighted for the size of MSM populations.
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.
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.

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.
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.Read More

11 022 documents were reviewed, graded, and catalogued by the Reference Group to the UN on HIV and Injecting Drug Use.
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 world's 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.
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.