The Impact of Opiate Substitution Therapy and Highly Active Antiretroviral Therapy on Mortality Risk Among People Who Inject Drugs

People who are currently injecting drugs are thought to comprise perhaps 5%–10% (approximately 3 million) of all human immunodeficiency virus (HIV)–infected people worldwide [1, 2], with an even greater number of peoplewith a history of injecting likely to be living with HIV. Historically, >40%of peoplewho inject drugs (PWID) in some high-income countries were thought to be HIV infected, with similarly high prevalence estimates more recently in some transitional developing countries [3]. Systematic reviews have shown that opioid substitution therapy (OST) can halve the risk of HIV transmission among PWID; there is also strengthening evidence that needle and syringe programs reduce injecting risk, HIV and other blood-borne virus transmissions [4–6]. Declines in HIV risk among PWID in Western European countries and the United States are thought to have been achieved largely through behavior change facilitated through scale-up of these critical interventions [7]. Model evaluations have also estimated that HIV transmission could be further reduced through early highly active antiretroviral therapy (HAART) (“treatment as prevention”), but little direct evidence has yet emerged [8]. Some studies have argued that ecological correlations between community measures of HIV RNA load and HIV incidence mean that HAART has decreased HIV transmission among PWID [9]. However, these changes occurred at the same time as decreases in hepatitis C virus (HCV) incidence, suggesting that a decrease in injecting risk (ie, behavior change) was also responsible. Pooled estimates from cohorts of PWID worldwide suggest that mortality may be 15 times higher than that of the general population [10]. Drug-related overdose is often the most common cause of death [11, 12]. The risk of mortality for PWID living with HIV is 3 times higher than that of HIV-uninfected PWID; PWID living with HIVmay also have a higher risk of overdose thanHIV-uninfected PWID [10]. Cohort studies of people with HIV have shown that HARRT improves survival, reducing both AIDS-related events and mortality risk [13]. PWID, however, tend to have lower survival than other patient groups living withHIV. It is assumed that this is because of the competing risk of overdose, hepatitis C infection, and HIV-related mortality, but also because of poorer overall HAART adherence and retention as well as delayed HAART onset following infection [14–16]. Methadone and buprenorphine, the most common pharmacological treatments for OST, were included in the list of the World Health Organization’s (WHO) “essential medicines” [17] in 2005. There is substantial evidence to show that OST reduces the risk of mortality, although the risk of mortality during treatment initiation and, in particular, following cessation can be elevated, suggesting that prevention benefit needs to be accrued through prolonged treatment [11, 18–20]. OST also can improve adherence to HAART [21, 22] and the subsequent treatment response [23], and therefore may reduce HIV-related mortality. However, to date, the evidence on impact of OST and HAART on mortality risk among PWID living with HIV is sparse [24]. This makes the study by Nosyk and colleagues in this issue of Clinical Infectious Diseases important [25]. Nosyk et al’s study is novel for 2 methodological reasons. First, the authors Received 8 June 2015; accepted 9 June 2015; electronically published 25 June 2015. Correspondence: Matthew Hickman, BSc, MSc, PhD, FFPH, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Road, Bristol BS8 2BN, UK (matthew.hickman@bristol.ac.uk). Clinical Infectious Diseases 2015;61(7):1166–8 © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/cid/civ481