[Commentary] ANTIRETROVIRAL THERAPY: A KEY PART OF THE PUBLIC HEALTH RESPONSE TO INJECTION DRUG USE

The United Nations Program on HIV/AIDS estimates that one-third of new HIV infections outside of sub-Saharan Africa are attributable to injection drug use [1]. As the HIV epidemic has evolved in this population, growing numbers of injection drug users (IDU) face premature morbidity and mortality without access to highly active antiretroviral therapy (HAART). However, compulsive drug-seeking behaviours, other co-morbid psychiatric illness and other IDU social characteristics such as homelessness can all severely complicate the delivery of appropriate HIV treatment to IDU [2,3]. As a result, it has been well demonstrated that physicians may be highly reluctant to prescribe HAART to HIV-infected IDU [3–6]. Prior studies have suggested that this reluctance may be attributable to the perception that IDU may be less likely to adhere to HAART [5,7–9]. Other physician concerns include the belief that IDU may be more likely to develop and transmit antiretroviral-resistant HIV [10]. These concerns may partially explain why patients with a history of injection drug use have lower rates of access to HAART, and why many HIV-infected patients die without ever accessing antiretrovirals, even in settings with free HIV/AIDS care [11]. In this issue of Addiction, Ferreros and colleagues report on patterns of mortality among a large and longstanding cohort of Spanish IDU recruited from AIDS Prevention and Information Centres of the Valencian Community between 1987 and 1996, and followed until 2004 [12]. Their adjusted analyses demonstrate a 50% reduction in AIDS mortality after the introduction of HAART in Spain in 1997. Interestingly, their analyses did not show any increases in mortality from causes (e.g. cardiovascular disease) that have been attributed to increased HAART exposure [13]. Although shorter term studies have reported reductions in HIV-related mortality among IDU coinciding with the introduction of HAART [14], the key contribution of the study is that it provides long-term populational estimates of the impact of HAART among IDU since its introduction in 1997. The key limitation of the Ferreros et al. study is that the investigators were unable to measure actual exposure to antiretroviral therapy among their cohort. Since a wealth of studies have shown how IDU may have lower access to antiretroviral therapy, the actual impact of HAART on survival of IDU in their study has likely been grossly underestimated [11,14]. For instance, in British Columbia, Canada, where all HIV/AIDS care and antiretroviral therapy is offered free of charge through a universal healthcare system, we have previously shown that one-third of HIV-related deaths occurred among individuals who had never accessed antiretrovirals [11]. Other settings have described similar problems with access to HAART among IDU. For instance, a recent audit of 50 developing and transitional countries estimated that IDU represented only 15% of individuals receiving HAART [15]. As such, there are likely three populations in the Ferreros et al. study: (i) HIV-negative IDU, (ii) HIV-infected IDU who accessed HAART, and (iii) HIV-infected IDU who did not access HAART. It would have been very interesting to know the actual changes in mortality among these two separate groups of HIV-infected IDU. While there are a host of concerns with access to HAART, including drug acquisition costs, one major and immediately modifiable concern with the current state of antiretroviral treatment for IDU is the discordance between physician perceptions and empirical evidence regarding the benefits of HAART use in this population [6,8,9,16]. For instance, although IDU are known to have lower levels of adherence, studies have repeatedly demonstrated that many IDU can manage high adherence to antiretroviral therapy [17]. Similarly, although concerns have been voiced about transmission of antiretroviral-resistant HIV in the community, studies have also indicated that the rate of development of antiretroviral resistance is similar between IDU and non-IDU for all classes of antiretrovirals [10]. It is believed that similar rates of resistance, despite the lower levels of adherence commonly found among IDU, are likely explained by the fact that many IDU are insufficiently adherent to select for resistant strains of HIV [10]. Accordingly, ethical analyses have specifically concluded that physicians should not withhold HAART from patients based on the presumption that they will be non-adherent, and this argument is strengthened by the studies that have consistently demonstrated that providers are poor judges of patient adherence [9,18]. The study by Ferreros and colleagues in this issue of Addiction highlights the massive contribution to improved survival among HIV-infected IDU coinciding with the introduction of antiretroviral therapy among IDU [12]. It bears repeating that the reductions in mortality which they have demonstrated are likely to be a gross underestimation of the potential populational survival benefits of HAART, since many IDU in their setting undoubtedly did not access antiretroviral therapy [11]. Nevertheless, in light of these benefits and the known issues with access to HAART among IDU, strategies to improve access to antiretroviral therapy among this population are urgently needed. In this context, addressing modifiable barriers such as the discordance between physician perceptions and empirical evidence regarding the benefits of HAART use among IDU should be prioritized, and the study by Ferreros and colleagues will make a valuable contribution to this effort. Julio Montaner has received educational grants from, served as an ad hoc adviser to or spoken at various events sponsored by Abbott Laboratories, Agouron Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals Inc., Borean Pharma AS, Bristol–Myers Squibb, DuPont Pharma, Gilead Sciences, GlaxoSmithKline, Hoffmann–La Roche, Immune Response Corporation, Incyte, Janssen–Ortho Inc., Kucera Pharmaceutical Company, Merck Frosst Laboratories, Pfizer Canada Inc., Sanofi Pasteur, Shire Biochem Inc., Tibotec Pharmaceuticals Ltd. and Trimeris Inc. We thank Deborah Graham for her comments on the manuscript.

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