EDITORIAL COMMENT
Securing opioid substitution treatment access and quality for people who inject drugs Maria Patrizia Carrieria,b,c, Luis Sagaon-Teyssiera,b,c and Perrine Rouxa,b,c See related paper on page 965 AIDS 2015, 29:975–976 Keywords: HAART, HIV/AIDS, opioid dependence, opioid substitution treatment
In this issue of AIDS, Nosyk et al. [1] present significant results about the causal effect of opioid substitution treatment (OST) on adherence to antiretroviral treatment (ART). Their study included a large database of 1852 HIV-infected, opioid-dependent individuals in British Columbia (Canada) and used a complex and consistent methodology to show the causal link between receiving OST and ART adherence. Their findings showed that individuals receiving OST are 70% more likely to be ART-adherent. Adherence assessment was based on pharmacy refill, which is an appropriate measure of ART discontinuation or interruption, two events that can seriously compromise ART success. This study represents a major advance in the field of access to care for people who inject drugs (PWID) for two main reasons. The first reason is related to the identification of a causal link between OST receipt and ART adherence using an innovative approach able to estimate the causal effect by controlling time-varying confounding in the exposure-outcome relationship. The time-varying relationship between OST and ART adherence expresses itself in several ways: individuals receiving OST are more likely to start ART and vice versa [2]; time on OST can stabilize their lives, promote healthy behaviours including ART adherence and foster long-
term virological response to ART in OST-ART treated patients [3]. To date, the statistical methods most used to study this relationship have been generalized linear models that consider that all potential predictors have the same level of importance in explaining the outcome (ART adherence). The difficulty to control such timevarying confounding using the classic methods of analysis has raised doubts about the causal effect of OST on ART success. Instead, the method used by Nosyk et al. [1] is based on a marginal structural model that offers the possibility to make causal inference, by accounting for the reciprocal interaction between OST and ART adherence in a longitudinal setting. The weights estimated in the first stage of the model allow the time-varying confounding of this relationship can be controlled for. Such weighting creates a pseudopopulation in which exposure is independent of the measured confounders [4]. The association found is also robust, as confirmed by sensitivity analyses. The second reason is related to the external validity of the results, as the causal relationship found, according to the authors, is valid under the Canadian model of care for HIV and opioid dependence, which is characterized by universal access to OST and ART for PWID. This model also implies OST receipt following international guidelines, that is appropriately prescribed OST dose to assure its effectiveness on opioid dependence [5].
a
INSERM, UMR912 (SESSTIM), bAix Marseille Universite´, UMR_S912, IRD, and cORS PACA, Observatoire Re´gional de la Sante´ Provence-Alpes-Coˆte d’Azur, Marseille, France. Correspondence to Maria Patrizia Carrieri, INSERM, UMR912 (SESSTIM) and ORS PACA, 23, rue S. Torrents 13006, Marseilles, France. E-mail: [email protected] Received: 11 January 2015; revised: 16 January 2015; accepted: 27 February 2015. DOI:10.1097/QAD.0000000000000641
ISSN 0269-9370 Copyright Q 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
975
976
AIDS
2015, Vol 29 No 8
Nevertheless, the results by Nosyk et al. [1] remain valid for many other countries already using or starting similar models for expanded and free access to care for PWID. These models also have public health benefits in the community of PWID because high ART/OST coverage is a guarantee of reduced risk of both sexual/ parenteral transmission [6] and HIV resistance because of sustained ART adherence [7]. Moreover, although free universal access to HIV and drug dependence care may seem an expensive model to some, the individual and public health benefits remain undeniable and outweigh the costs [2]. The key message of this study is that OSTenhances ART adherence (and ensures long-term response to ART) if both treatments are accessible, free and if there are no major structural barriers causing treatment interruptions. Despite the considerable effort by countries in tackling drug-use driven HIV epidemics [8], several structural barriers continue to compromise the effectiveness of comprehensive OST/ART. In many countries, PWID report that fear of registration is a deterrent to seeking treatment, as individuals must accept to have their names added to government registries shared with the police [2]. Moreover, although OST programmes are slowly replacing drug detention centres in many regions in Malaysia, Vietnam and China, police crackdowns and imprisonment still constitute a major cause of OST and ART discontinuation [8]. The lack of training of prescribing physicians may result in inappropriate doses being prescribed or drug abstinence during OST being requested, both of which can cause drop-outs and relapse into drug use [8]. It is also clear that asking PWID – a group with very limited resources that has an easy access to the drug market – for additional fees for treatment can compromise any attempt at social insertion. Armed conflict can also have dramatic repercussions on OSTaccess. One particular case is Ukraine, a country with one of the highest prevalences of HIV among drug users, where the vast OST programme was introduced as a joint governmental and civil society initiative [9]. Following the recent annexation of the Crimean Autonomous Republic and the city of Sevastopol by the Russian Federation, Russia has prohibited OST in these areas. Consequently, the Ukrainian government has had to implement a pragmatic plan to ensure continuity of OST, HIV and tuberculosis (TB) treatment for patients who have moved to other parts of Ukraine [9]. All these structural barriers threaten OST access and quality, and discredit its effectiveness as an individual and public health intervention. An international global initiative continues to be needed to promote and secure optimal OST-ART models of care for PWID.
The rising use of stimulants and synthetic drugs worldwide and particularly in some Asian countries [10] is a rising health problem requiring innovative responses to reduce their harms. Support for pragmatic research to address HIV risk or ART failure in stimulant and synthetic drug users is urgently needed and requires a comprehensive multidisciplinary approach to address and coordinate targeted public health actions in a timely manner. To conclude, the results from Nosyck et al. [1] represent the final step in confirming the relationship between optimized OST delivery and ART response in drugusing populations. International efforts are now needed to continue the scale-up of similar models of care and to secure existing models, especially in critical contexts.
Acknowledgements Conflicts of interest There are no conflicts of interest.
References 1. Nosyk B, Min JE, Colley G, Lima VD, Yip B, Milloy MJS, et al. The causal effect of opioid substitution treatment on HAART medication refill adherence. AIDS 2015; 29:965–973. 2. Wolfe D, Carrieri MP, Shepard D. Treatment and care for injecting drug users with HIV infection: a review of barriers and ways forward. Lancet 2010; 376:355–366. 3. Roux P, Carrieri MP, Cohen J, Ravaux I, Poizot-Martin I, Dellamonica P, et al. Retention in opioid substitution treatment: a major predictor of long-term virological success for HIV-infected injection drug users receiving antiretroviral treatment. Clin Infect Dis 2009; 49:1433–1440. 4. Cole SR, Hernan MA. Constructing inverse probability weights for marginal structural models. Am J Epidemiol 2008; 168:656– 664. 5. World Health Organization. Dept. of Mental Health and Substance Abuse. International Narcotics Control Board. United Nations Office on Drugs and Crime. Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. Geneva: World Health Organization; 2009. 6. Wood E, Kerr T, Marshall BD, Li K, Zhang R, Hogg RS, et al. Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: prospective cohort study. BMJ 2009; 338:b1649. 7. Wood E, Hogg RS, Yip B, Dong WW, Wynhoven B, Mo T, et al. Rates of antiretroviral resistance among HIV-infected patients with and without a history of injection drug use. AIDS 2005; 19:1189–1195. 8. Degenhardt L, Mathers BM, Wirtz AL, Wolfe D, Kamarulzaman A, Carrieri MP, et al. What has been achieved in HIV prevention, treatment and care for people who inject drugs, 2010– 2012? A review of the six highest burden countries. Int J Drug Policy 2014; 25:53–60. 9. Filippovych S. Impact of armed conflicts and warfare on opioid substitution treatment in Ukraine: responding to emergency needs. Int J Drug Policy 2015; 26:3–5. 10. Wu Z, Wang Y, Detels R, Bulteryes M. Towards ending HIV/ AIDS among drug users in China. Addiction 2014; 110:1–3.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Securing opioid substitution treatment access and quality for people who inject drugs Maria Patrizia Carrieria,b,c, Luis Sagaon-Teyssiera,b,c and Perrine Rouxa,b,c See related paper on page 965 AIDS 2015, 29:975–976 Keywords: HAART, HIV/AIDS, opioid dependence, opioid substitution treatment
In this issue of AIDS, Nosyk et al. [1] present significant results about the causal effect of opioid substitution treatment (OST) on adherence to antiretroviral treatment (ART). Their study included a large database of 1852 HIV-infected, opioid-dependent individuals in British Columbia (Canada) and used a complex and consistent methodology to show the causal link between receiving OST and ART adherence. Their findings showed that individuals receiving OST are 70% more likely to be ART-adherent. Adherence assessment was based on pharmacy refill, which is an appropriate measure of ART discontinuation or interruption, two events that can seriously compromise ART success. This study represents a major advance in the field of access to care for people who inject drugs (PWID) for two main reasons. The first reason is related to the identification of a causal link between OST receipt and ART adherence using an innovative approach able to estimate the causal effect by controlling time-varying confounding in the exposure-outcome relationship. The time-varying relationship between OST and ART adherence expresses itself in several ways: individuals receiving OST are more likely to start ART and vice versa [2]; time on OST can stabilize their lives, promote healthy behaviours including ART adherence and foster long-
term virological response to ART in OST-ART treated patients [3]. To date, the statistical methods most used to study this relationship have been generalized linear models that consider that all potential predictors have the same level of importance in explaining the outcome (ART adherence). The difficulty to control such timevarying confounding using the classic methods of analysis has raised doubts about the causal effect of OST on ART success. Instead, the method used by Nosyk et al. [1] is based on a marginal structural model that offers the possibility to make causal inference, by accounting for the reciprocal interaction between OST and ART adherence in a longitudinal setting. The weights estimated in the first stage of the model allow the time-varying confounding of this relationship can be controlled for. Such weighting creates a pseudopopulation in which exposure is independent of the measured confounders [4]. The association found is also robust, as confirmed by sensitivity analyses. The second reason is related to the external validity of the results, as the causal relationship found, according to the authors, is valid under the Canadian model of care for HIV and opioid dependence, which is characterized by universal access to OST and ART for PWID. This model also implies OST receipt following international guidelines, that is appropriately prescribed OST dose to assure its effectiveness on opioid dependence [5].
a
INSERM, UMR912 (SESSTIM), bAix Marseille Universite´, UMR_S912, IRD, and cORS PACA, Observatoire Re´gional de la Sante´ Provence-Alpes-Coˆte d’Azur, Marseille, France. Correspondence to Maria Patrizia Carrieri, INSERM, UMR912 (SESSTIM) and ORS PACA, 23, rue S. Torrents 13006, Marseilles, France. E-mail: [email protected] Received: 11 January 2015; revised: 16 January 2015; accepted: 27 February 2015. DOI:10.1097/QAD.0000000000000641
ISSN 0269-9370 Copyright Q 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
975
976
AIDS
2015, Vol 29 No 8
Nevertheless, the results by Nosyk et al. [1] remain valid for many other countries already using or starting similar models for expanded and free access to care for PWID. These models also have public health benefits in the community of PWID because high ART/OST coverage is a guarantee of reduced risk of both sexual/ parenteral transmission [6] and HIV resistance because of sustained ART adherence [7]. Moreover, although free universal access to HIV and drug dependence care may seem an expensive model to some, the individual and public health benefits remain undeniable and outweigh the costs [2]. The key message of this study is that OSTenhances ART adherence (and ensures long-term response to ART) if both treatments are accessible, free and if there are no major structural barriers causing treatment interruptions. Despite the considerable effort by countries in tackling drug-use driven HIV epidemics [8], several structural barriers continue to compromise the effectiveness of comprehensive OST/ART. In many countries, PWID report that fear of registration is a deterrent to seeking treatment, as individuals must accept to have their names added to government registries shared with the police [2]. Moreover, although OST programmes are slowly replacing drug detention centres in many regions in Malaysia, Vietnam and China, police crackdowns and imprisonment still constitute a major cause of OST and ART discontinuation [8]. The lack of training of prescribing physicians may result in inappropriate doses being prescribed or drug abstinence during OST being requested, both of which can cause drop-outs and relapse into drug use [8]. It is also clear that asking PWID – a group with very limited resources that has an easy access to the drug market – for additional fees for treatment can compromise any attempt at social insertion. Armed conflict can also have dramatic repercussions on OSTaccess. One particular case is Ukraine, a country with one of the highest prevalences of HIV among drug users, where the vast OST programme was introduced as a joint governmental and civil society initiative [9]. Following the recent annexation of the Crimean Autonomous Republic and the city of Sevastopol by the Russian Federation, Russia has prohibited OST in these areas. Consequently, the Ukrainian government has had to implement a pragmatic plan to ensure continuity of OST, HIV and tuberculosis (TB) treatment for patients who have moved to other parts of Ukraine [9]. All these structural barriers threaten OST access and quality, and discredit its effectiveness as an individual and public health intervention. An international global initiative continues to be needed to promote and secure optimal OST-ART models of care for PWID.
The rising use of stimulants and synthetic drugs worldwide and particularly in some Asian countries [10] is a rising health problem requiring innovative responses to reduce their harms. Support for pragmatic research to address HIV risk or ART failure in stimulant and synthetic drug users is urgently needed and requires a comprehensive multidisciplinary approach to address and coordinate targeted public health actions in a timely manner. To conclude, the results from Nosyck et al. [1] represent the final step in confirming the relationship between optimized OST delivery and ART response in drugusing populations. International efforts are now needed to continue the scale-up of similar models of care and to secure existing models, especially in critical contexts.
Acknowledgements Conflicts of interest There are no conflicts of interest.
References 1. Nosyk B, Min JE, Colley G, Lima VD, Yip B, Milloy MJS, et al. The causal effect of opioid substitution treatment on HAART medication refill adherence. AIDS 2015; 29:965–973. 2. Wolfe D, Carrieri MP, Shepard D. Treatment and care for injecting drug users with HIV infection: a review of barriers and ways forward. Lancet 2010; 376:355–366. 3. Roux P, Carrieri MP, Cohen J, Ravaux I, Poizot-Martin I, Dellamonica P, et al. Retention in opioid substitution treatment: a major predictor of long-term virological success for HIV-infected injection drug users receiving antiretroviral treatment. Clin Infect Dis 2009; 49:1433–1440. 4. Cole SR, Hernan MA. Constructing inverse probability weights for marginal structural models. Am J Epidemiol 2008; 168:656– 664. 5. World Health Organization. Dept. of Mental Health and Substance Abuse. International Narcotics Control Board. United Nations Office on Drugs and Crime. Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. Geneva: World Health Organization; 2009. 6. Wood E, Kerr T, Marshall BD, Li K, Zhang R, Hogg RS, et al. Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: prospective cohort study. BMJ 2009; 338:b1649. 7. Wood E, Hogg RS, Yip B, Dong WW, Wynhoven B, Mo T, et al. Rates of antiretroviral resistance among HIV-infected patients with and without a history of injection drug use. AIDS 2005; 19:1189–1195. 8. Degenhardt L, Mathers BM, Wirtz AL, Wolfe D, Kamarulzaman A, Carrieri MP, et al. What has been achieved in HIV prevention, treatment and care for people who inject drugs, 2010– 2012? A review of the six highest burden countries. Int J Drug Policy 2014; 25:53–60. 9. Filippovych S. Impact of armed conflicts and warfare on opioid substitution treatment in Ukraine: responding to emergency needs. Int J Drug Policy 2015; 26:3–5. 10. Wu Z, Wang Y, Detels R, Bulteryes M. Towards ending HIV/ AIDS among drug users in China. Addiction 2014; 110:1–3.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
