Pre-implementation findings on the barriers and potential solutions to initiate same-day antiretroviral therapy among people who inject drugs in Malaysia.

Worldwide, people who inject drugs (PWID) are a key population disproportionally affected by HIV and hepatitis C (HCV) primarily through the sharing of injecting equipment. Despite this, in Australia an early and continued comprehensive harm reduction response has resulted in HIV prevalence in PWID of 1-2%, HCV prevalence among PWID remains over 50%. This thesis sought to investigate the degree to which PWID are accepted into and progress through the continuum of effective HIV and HCV clinical care, as well as consider the impact of the current revolution in HCV small molecule antiviral therapy for PWID. A range of quantitative and qualitative methods were used to explore the relationship between PWID, HIV and HCV diagnosis, and treatment. The major findings of this thesis following an analysis of 3 longitudinal datasets in Victoria, Australia are that PWID are less likely to present late, and more likely to present early, for HIV diagnosis than non-injectors and that HIV-infected PWID in Victoria achieve equivalent HIV treatment outcomes following initiation of combination antiretroviral therapy (cART), including in their likelihood of obtaining HIV viral load suppression, compared with non-injectors. The thesis explored the utility of a HCV notification system in Victoria to identify PWID with newly acquired HCV and to link to treatment for acute HCV. While the rate of treatment uptake is low, this provides an epidemiological mechanism to confirm acute HCV diagnosis and link individuals to treatment. Qualitative methods were used to explore HCV interferon-based treatment for PWID in the community setting.While PWID find the current standard of care interferon-based HCV therapy challenging, there may be a positive subjective impact on substance use following completion of treatment. In addition, peer support for PWID is feasible and acceptable to PWID undergoing HCV treatment, is associated with high rates of treatment uptake and may assist with retention in community-based treatment settings. The current situation regarding PWID and new direct-acting antivirals (DAAs) was reviewed. Interferon-free regimens consisting of these new, highly effective DAAs have the potential to revolutionize HCV therapy. Despite being a key affected population, PWID are unlikely to benefit from these new treatments because of price and access barriers. Taken together, the findings of this thesis suggest that timely diagnosis and effective care and treatment of both HIV and HCV is possible for PWID, and potentially enhanced by peer workers attached to the clinical team in the context of treatment.

IntroductionEmerging HIV epidemics have been documented among people who inject drugs (PWID) in the Middle East and North Africa (MENA). This study estimates the HIV incidence among PWID due to sharing needles/syringes in MENA. It also delineates injecting drug use role as a driver of the epidemic in the population, and estimates impact of interventions.MethodsA mathematical model of HIV transmission among PWID was applied in seven MENA countries with sufficient and recent epidemiological data and HIV prevalence ≥1% among PWID. Estimations of incident and/or prevalent infections among PWID, ex‐PWID and sexual partners of infected current and ex‐PWID were conducted.ResultsThe estimated HIV incidence rate for 2017 among PWID ranged between 0.7% per person‐year (ppy) in Tunisia and 7.8% ppy in Pakistan, with Libya being an outlier (24.8% ppy). The estimated number of annual new infections was lowest in Tunisia (n = 79) and Morocco (n = 99), and highest in Iran and Pakistan (approximately n = 6700 each). In addition, 20 to 2208 and 5 to 837 new annual infections were estimated across the different countries among sexual partners of PWID and ex‐PWID respectively. Since epidemic emergence, the number of total ever acquired incident infections across countries was 706 to 90,015 among PWID, 99 to 18,244 among sexual partners of PWID, and 16 to 4360 among sexual partners of ex‐PWID. The estimated number of prevalent infections across countries was 341 to 23,279 among PWID, 119 to 16,540 among ex‐PWID, 67 to 10,752 among sexual partners of PWID, and 12 to 2863 among sexual partners of ex‐PWID. Increasing antiretroviral therapy (ART) coverage to the global target of 81% – factoring in ART adherence and current coverage – would avert about half of new infections among PWID and their sexual partners. Combining ART with harm reduction could avert over 90% and 70% of new infections among PWID and their sexual partners respectively.ConclusionsThere is considerable HIV incidence among PWID in MENA. Of all new infections ultimately due to injecting drug use, about 75% are among PWID and the rest among sexual partners. Of all prevalent infections ultimately attributed to injecting drug use as epidemic driver, about half are among PWID, 30% among ex‐PWID and 20% among sexual partners of PWID and ex‐PWID. These findings call for scale‐up of services for PWID, including harm reduction as well as testing and treatment services.

BackgroundStigma, criminalisation and a lack of data on drug use contribute to the “invisibility” of people who inject drugs (PWID) and make HIV prevention and treatment service delivery challenging. We aimed to confirm locations where PWID congregate in Cape Town, eThekwini and Tshwane (South Africa) and to estimate PWID population sizes within selected electoral wards in these areas to inform South Africa’s first multi-site HIV prevention project for PWID.MethodsField workers (including PWID peers) interviewed community informants to identify suspected injecting locations in selected electoral wards in each city and then visited these locations and interviewed PWID. Interviews were used to gather information about the accessibility of sterile injecting equipment, location coordinates and movement patterns. We used the Delphi method to obtain final population size estimates for the mapped wards based on estimates from wisdom of the crowd methods, the literature and programmatic data.ResultsBetween January and April 2015, we mapped 45 wards. Tshwane teams interviewed 39 PWID in 12 wards, resulting in an estimated number of accessible PWID ranging from 568 to 1431. In eThekwini, teams interviewed 40 PWID in 15 wards with an estimated number of accessible PWID ranging from 184 to 350. The Cape Town team interviewed 61 PWID in 18 wards with an estimated number of accessible PWID ranging between 398 and 503. Sterile needles were only available at one location. Almost all needles were bought from pharmacies. Between 80 and 86% of PWID frequented more than one location per day. PWID who reported movement visited a median of three locations a day.ConclusionsProgrammatic mapping led by PWID peers can be used effectively to identify and reach PWID and build relationships where access to HIV prevention commodities for PWID is limited. PWID reported limited access to sterile injecting equipment, highlighting an important HIV prevention need. Programmatic mapping data show that outreach programmes should be flexible and account for the mobile nature of PWID populations. The PWID population size estimates can be used to develop service delivery targets and as baseline measures.

Community health workers: A bridge to healthcare for people who inject drugs

Commentary Asia and the Pacific region is one of the world’s most vibrant places in terms of economic growth and social advancement. It captures many superlatives: the planet’s highest proportion of young people, the largest megacities in the world and Asia wins the crown of global growth leader again and again. However, despite the dynamism, some citizens are falling through the cracks. This is particularly true for people who inject drugs (PWID). With 3.15 million PWID, in terms of sheer numbers, East Asia and Southeast Asia has the largest injecting drug problem in the world and is home to one in four PWID globally [1]. People who inject drugs have multiple vulnerabilities—to HIV, hepatitis, tuberculosis and other infectious diseases; they account for an estimated 30 % of new HIV infections outside sub-Saharan Africa. About a third of PWID are living with HIV in Southwest Asia [1], and a number of countries have reported HIV prevalence higher than 10 % [2]. National figures often do not tell the full story, with some localities reporting significantly higher prevalence. In Cebu City, Philippines, HIV prevalence among PWID was estimated at 52.3 % in 2013 [3], and in Faisalabad, Pakistan, it was as high as 52.5 % in 2011 [4]. Scientific evidence shows that to respond to HIV and other health risks of people who inject drugs, it is important to develop programmes which cater to their needs. The Joint United Nations Programme on HIV/ AIDS (UNAIDS), the United Nations Office on Drugs and Crime (UNODC) and the World Health Organization (WHO) have recommended a package of nine interventions, commonly referred to as the comprehensive approach to injecting drug use [5]. The first four interventions—needle-syringe programmes (NSP), opioid substitution therapy (OST), HIV testing and counselling and the provision of antiretroviral therapy (ART)—are critical for effective national programmes. There is compelling evidence that NSP and OST are effective in reducing the sharing of injecting equipment and averting HIV infections. In combination with ART, these interventions diminish HIV transmission, decrease mortality, reduce drug dependency and improve quality of life. Several countries in the region have taken these recommendations to heart and implemented parts of the comprehensive harm reduction package. In the late 1990s, China had a fast-growing HIV epidemic among people who inject drugs and its health authorities began introducing OST sites and needle-syringe programmes. By the end of 2014, more than 700 OST sites were operating in China. HIV incidence rate dropped by 87.6 % from 0.95 % in 2006 to 0.12 % in 2014 among those registered in the clinics [6]. Recently, India and Myanmar have also increased their OST coverage. Despite these pockets of success, the coverage of harm reduction programmes remains inadequate in Asia and the Pacific region. High coverage of needle-syringe programmes is defined by WHO, UNAIDS and UNODC as more than 200 needles or syringes provided per PWID a year. Only four countries reported reaching high coverage in 2014, and five reported that less than 50 % of PWID used clean equipment for their last injection [2]. PWID frequently face stigma and discrimination when seeking health services and are far less likely to receive ART than others living with HIV due to social marginalization and the flawed perception that they are unable to adhere to treatment effectively. While current national monitoring systems are not designed to capture data on access to ART for PWID, a recent review suggests that less than five PWID received ART per 100 HIV-positive PWID [7]. Not only is coverage low, but there are worrying signs that some countries with a high HIV burden among PWID are scaling down harm reduction interventions [8]. This is undoubtedly due to the phasing out of support by international donors with little new funds * Correspondence: KrausS@unaids.org UNAIDS Regional Support Team for Asia and the Pacific, United Nations Building, Rajadamnern Nok Avenue, Bangkok 10200, Thailand Full list of author information is available at the end of the article

Potential impact of implementing and scaling up harm reduction and antiretroviral therapy on HIV prevalence and mortality and overdose deaths among people who inject drugs in two Russian cities: a modelling study

IntroductionThe HIV epidemic in Tijuana, Mexico is concentrated in key populations, including people who inject drugs (PWID). However, HIV interventions among PWID are minimal, and federal funding was provided for compulsory abstinence programmes associated with HIV and overdose. Alternatively, opioid agonist therapy reduces overdose, reincarceration, HIV, while improving antiretroviral therapy (ART) outcomes. We assessed potential impact and synergies of scaled‐up integrated ART and opioid agonist therapy, compared to scale‐up of each separately, and potential harms of compulsory abstinence programmes on HIV and fatal overdose among PWID in Tijuana.MethodsWe developed a dynamic model of HIV transmission and overdose among PWID in Tijuana. We simulated scale‐up of opioid agonist therapy from zero to 40% coverage among PWID. We evaluated synergistic benefits of an integrated harm reduction and ART scale‐up strategy (40% opioid agonist therapy coverage and 10‐fold ART recruitment), compared to scale‐up of each intervention alone or no scale‐up of low coverage ART and no harm reduction). We additionally simulated compulsory abstinence programmes (associated with 14% higher risk of receptive syringe sharing and 76% higher odds of overdose) among PWID.ResultsWithout intervention, HIV incidence among PWID could increase from 0.72 per 100 person‐years (PY) in 2020 to 0.92 per 100 PY in 2030. Over ten years, opioid agonist therapy scale‐up could avert 31% (95% uncertainty interval (UI): 18%, 46%) and 22% (95% UI: 10%, 28%) new HIV infections and fatal overdoses, respectively, with the majority of HIV impact from the direct effect on HIV transmission due to low ART coverage. Integrating opioid agonist therapy and ART scale‐up provided synergistic benefits, with opioid agonist therapy effects on ART recruitment/retention averting 9% more new infections compared to ART scale‐up alone. The intervention strategy could avert 48% (95% UI: 26%, 68%) of new HIV infections and one‐fifth of fatal overdoses over ten years. Conversely, compulsory abstinence programmes could increase HIV and overdoses.ConclusionsIntegrating ART with opioid agonist therapy could provide synergistic benefits and prevent HIV and overdoses among PWID in Tijuana, whereas compulsory abstinence programmes could cause harm. Policymakers should consider the benefits of integrating harm reduction and HIV services for PWID.

HIV and people who use drugs in central Asia: Confronting the perfect storm

BackgroundAbout a third of the global HIV infections outside sub-Saharan Africa are related to injecting drug use (IDU), and this accounts for a growing proportion of persons living with HIV. This paper is a response to the need to monitor the state of the HIV epidemic as it relates to IDU and the availability of HIV treatment and harm reduction services in 21 high epidemic countries.MethodsA data collection form was designed to cover questions on rates of IDU, prevalence and incidence of HIV and information on HIV treatment and harm reduction services available to people who inject drugs (PWID). National and regional data on HIV infection, IDU in the form of reports and journal articles were sought from key informants in conjunction with a systematic search of the literature.ResultsCompleted data collection forms were received for 11 countries. Additional country-specific information was sourced via the literature search. The overall proportion of HIV positive PWID in the selected countries ranged from 3% in Kazakhstan to 58% in Vietnam. While IDU is relatively rare in sub-Saharan Africa, it is the main driver of HIV in Mauritius and Kenya, with roughly 47% and 36% of PWID respectively being HIV positive. All countries had antiretroviral treatment (ART) available to PWID, but data on service coverage were mainly missing. By the end of 2010, uptake of needle and syringe programmes (NSP) in Bangladesh, India and Slovakia reached the internationally recommended target of 200 syringes per person, while uptake in Kazakhstan, Vietnam and Tajikistan reached between 100-200 syringes per person. The proportion of PWID receiving opioid substitution therapy (OST) ranged from 0.1% in Kazakhstan to 32.8% in Mauritius, with coverage of less than 3% for most countries.ConclusionsIn order to be able to monitor the impact of HIV treatment and harm reduction services for PWID on the epidemic, epidemiological data on IDU and harm reduction service provision to PWID needs to be regularly collected using standardised indicators.

BackgroundWHO, UNODC, and UNAIDS recommend a comprehensive package for prevention, treatment, and care of HIV among people who inject drugs (PWID). We describe the uptake of services and the cost of implementing a comprehensive package for HIV prevention, treatment, and care services in Delhi, India.MethodsA cohort of 3774 PWID were enrolled for a prospective HIV incidence study and provided the comprehensive package: HIV and hepatitis testing and counseling, hepatitis B (HB) vaccination, syndromic management of sexually transmitted infections, clean needles-syringes, condoms, abscess care, and education. Supplementary services comprising tea and snacks, bathing facilities, and medical consultations were also provided. PWID were referred to government services for antiretroviral therapy (ART), TB care, opioid substitution therapy, and drug dependence treatment/rehabilitation.ResultsThe project spent USD 1,067,629.88 over 36 months of project implementation: 1.7% on capital costs, 3.9% on participant recruitment, 26.7% for project management, 49.9% on provision of services, and 17.8% on supplementary services. Provision of HIV prevention and care services cost the project USD 140.41/PWID/year. 95.3% PWID were tested for HIV. Of the HIV-positive clients, only 17.8% registered for ART services after repeated follow-up. Reasons for not seeking ART services included not feeling sick, need for multiple visits to the clinic, and long waiting times. 61.8% of the PWID underwent HB testing. Of the 2106 PWID eligible for HB vaccination, 81% initiated the vaccination schedule, but only 29% completed all three doses, despite intensive follow-up by outreach workers. PWID took an average of 8 clean needles-syringes/PWID/year over the project duration, with a mid-project high of 16 needles-syringes/PWID/year. PWID continued to also procure needles from other sources, such as chemists. One hundred five PWID were referred to OST services and 267 for rehabilitation services.ConclusionsA comprehensive HIV prevention, treatment, and care package is challenging to implement. Extensive efforts are needed to ensure the uptake of and retention in services for PWID; peer educators and outreach workers are required on a continuous basis. Services need to be tailored to client needs, considering clinic timing and distance from hotspots. Programs may consider provision of ART services at selected drop-in centers to increase uptake.

How cost‐effective is hepatitis C virus treatment for people who inject drugs?

The new direct-acting antiretroviral drugs for treating hepatitis C have generated considerable momentum for treating HCV infection among people who inject drugs and perhaps ‘ending the HCV epidemic’. There are, however, important epidemiological and behavior research problems that need to be addressed before ‘ending the HCV epidemic’ will be possible. The development of direct-acting antivirals (DAAs) that cure HCV infection in more than 90% of patients with minimal side effects has led to calls for ‘eliminating HCV infection’ or ‘ending HCV epidemics’ among people who inject drugs (PWID) 1. Some of the calls for eliminating HCV infection have included substantial allocations of new funds, e.g. New York State 2. Grebely et al. 3 have estimated the number and prevalence of people with a recent history (within past year) of injecting drug use who are living with hepatitis C virus (HCV) viremia and the proportion of people with recent injecting drug use among all people living with HCV infection at the global, regional and national levels. A major value of this study is its potential contribution as a baseline for ‘eliminating HCV’. While DAAs and the lessons from successfully controlling HIV among PWID in many areas 4 should certainly be useful in controlling HCV among PWID, the data presented in Grebely et al. illustrate that there is still a major amount of epidemiological and behavioral science that will be needed before ‘eliminating’ (or even ‘controlling’) HCV among PWID can be accomplished. First, what would ‘elimination/ending the epidemic’ of HCV among PWID look like? From early in the HIV epidemic among PWID, we had multiple examples, e.g. Glasgow, Scotland, Lund, Sweden, Sydney, Australia and Tacoma, WA, USA, where large-scale implementation of syringe access programs have kept HIV prevalence stable at less than 5% 5. The Grebely et al. data do not provide many (if any) examples of areas where HCV viremia has been stabilized at ‘ending the epidemic’ levels. Would 5% viremia in the local PWID population be a realistic goal? What sort of HCV combined prevention and care programs would be needed to stabilize HCV at 5% or less in a PWID population? Such a system would need to detect and treat existing cases of HCV infection as rapidly as new infections were occurring. Secondly, how will we develop better estimates of the size of PWID populations and the percentage of PWID who are HCV viremic? The uncertainty intervals in the Grebely et al. estimates are rather large, typically almost as large as the estimates themselves. Uncertainty in the estimates of the PWID population size and the percentage of PWID who are HCV viremic would create difficult problems for local officials who would have the task of allocating resources and planning logistical operations for rapidly scaling-up treatment for HCV-infected PWID. Thirdly, what new interventions can be developed to reduce HCV transmission behavior among viremic PWID? One of the important factors in HIV prevention was that PWID who learned that they were HIV-seropositive greatly reduced transmission behavior (passing their used needles and syringes to others) well before antiretroviral therapy (ART) was available 6. We have not yet seen the equivalent reductions in transmission behaviors among PWID who know that they are HCV-seropositive 7. How do we successfully encourage HCV viremic PWID to reduce transmission behavior? Fourthly, what interventions can be developed and implemented to reduce the very high HCV incidence rates among people who have recently begun injecting drugs 8? Many new injectors typically do not identify as ‘drug injectors’, and thus do not utilize HIV/HCV safer injection programs 9. Fifthly, what interventions will be implemented to reduce the rates that drug users transition to injecting drug use? There have been calls for more research on this topic 10, and there are current research studies addressing this subject. However, the objective should be to develop an evidence base for reducing initiation into injecting drug use that is comparable to the evidence base for medication assisted treatment and for syringe access programs. The new DAAs certainly give us the capability of treating very large numbers of HCV infected people who use drugs and greatly reduce morbidity and mortality, and programs to provide access to HCV treatment should be scaled-up in high-, middle- and low-income countries as quickly as feasible, and the additional research needed to learn how to ‘end HCV epidemics’ among PWID should be funded. Finally, and perhaps most importantly, while the above may be considered scientific tasks, it is important to emphasize that the research should be conducted in full collaboration with PWID and drug-user organizations. Such collaboration should not only greatly improve the quality of the research, but also greatly improve the likelihood that the findings will be incorporated into public health programs that could ‘end the HCV epidemic’ among people who use drugs. None.

Achievement of viral load suppression among people living with HIV is one of the most important goals for effective HIV epidemic response. In Ukraine, people who inject drugs (PWID) experience the largest HIV burden. At the same time, this group disproportionally missed out in HIV treatment services. We performed a secondary data analysis of the national-wide cross-sectional bio-behavioral surveillance survey among PWID to assess the population-level prevalence of detectable HIV viremia and identify key characteristics that explain the outcome. Overall, 11.4% of PWID or 52.6% of HIV-positive PWID had a viral load level that exceeded the 1,000 copies/mL threshold. In the group of HIV-positive PWID, the detectable viremia was attributed to younger age, monthly income greater than minimum wage, lower education level, and non-usage of antiretroviral therapy (ART) and opioid agonistic therapy. Compared with HIV-negative PWID, the HIV-positive group with detectable viremia was more likely to be female, represented the middle age group (35–49 years old), had low education and monthly income levels, used opioid drugs, practiced risky injection behavior, and had previous incarceration history. Implementing the HIV case identification and ART linkage interventions focused on the most vulnerable PWID sub-groups might help closing the gaps in ART service coverage and increasing the proportion of HIV-positive PWID with viral load suppression.

Achievement of viral load suppression among people living with HIV is one of the most important goals for effective HIV epidemic response. In Ukraine, people who inject drugs (PWID) experience the largest HIV burden. At the same time, this group disproportionally missed out in HIV treatment services. We performed a secondary data analysis of the national-wide cross-sectional bio-behavioral surveillance survey among PWID to assess the population-level prevalence of detectable HIV viremia and identify key characteristics that explain the outcome. Overall, 11.4% of PWID or 52.6% of HIV-positive PWID had a viral load level that exceeded the 1,000 copies/mL threshold. In the group of HIV-positive PWID, the detectable viremia was attributed to younger age, monthly income greater than minimum wage, lower education level, and non-usage of antiretroviral therapy (ART) and opioid agonistic therapy. Compared with HIV-negative PWID, the HIV-positive group with detectable viremia was more likely to be female, represented the middle age group (35-49 years old), had low education and monthly income levels, used opioid drugs, practiced risky injection behavior, and had previous incarceration history. Implementing the HIV case identification and ART linkage interventions focused on the most vulnerable PWID sub-groups might help closing the gaps in ART service coverage and increasing the proportion of HIV-positive PWID with viral load suppression.

Injecting drug use is an important public health issue, causing significant morbidity and mortality worldwide. The contemporary drug market setting in Australia is defined by a lower prevalence and frequency of heroin injection among regular people who inject drugs (PWID) compared with in the past, and changing patterns of polydrug use, with some evidence of increasing use of pharmaceutical opioids. Our understanding of patterns of drug use and related risk behaviours among contemporary PWID is limited by the fact that much research has captured samples of predominantly older, long-term PWID, many of whom are on opioid substitution therapy (OST) and may use drugs only infrequently. The aim of the research presented in this thesis was to generate comprehensive information about patterns of drug use and associated risk behaviours among PWID who are active in contemporary settings, including understudied populations such as younger PWID, out-of-treatment PWID and PWID from culturally and linguistically diverse backgrounds. The Melbourne Injecting Drug User Cohort Study (MIX) is a prospective cohort of 688 community-recruited regular PWID. The median age of the cohort is 27.6 years and only 35% of participants were prescribed OST at baseline. Over 70% of the cohort completed a follow-up interview at 12 months post-baseline, demonstrating that it is possible to successfully retain a cohort of community-recruited PWID. Despite the uniqueness of this cohort, patterns of drug use by MIX participants were relatively similar to those displayed by sentinel samples of older, longer-term PWID. There were few differences in injecting initiation experiences between MIX participants who initiated injecting in contemporary settings and those who initiated in earlier settings and, although this had some ongoing impact, the relationship was not strongly related to current drug use patterns. Pharmaceutical opioid use was a key component of polydrug use among MIX participants, with 20% of the cohort reporting using illicitly-obtained pharmaceutical opioids in the month preceding baseline interview. Use of pharmaceutical opioids was however not sustained over time. The relationship between age and engagement in risk behaviours was examined using 10 years of data from the Australian Illicit Drug Reporting System, a national repeat cross-sectional survey of regular PWID recruited through needle and syringe programs, drug treatment and community settings. Older age was associated with decreased likelihood of engagement in a range of injecting-related and criminogenic risk behaviours. Injecting drug use among young people of African ethnicity was examined using MIX data and an additional qualitative study. Findings showed that injecting drug use (and substance use more broadly) and mental health are emerging issues among this community. Findings from this body of research inform the provision of harm reduction services which take into the account the key populations and patterns of drug use in the contemporary setting. Priority areas for future research include further research examining pharmaceutical opioid use among PWID, studies of substance use and mental health among resettled refugee youth, research into interventions to reduce injecting-related risk behaviours among younger PWID and additional longitudinal studies of PWID with a broader geographic focus.