Milloy et al make1 a key contribution in understanding the role of 2 environmental factors, involvement in the sex trade and incarceration, in undermining antiretroviral therapy (ART) success among people who use drugs (PWUD). Consistent with previous results,2 the authors also show that receiving methadone treatment during ART significantly improves long-term virological response to ART for those who are opiate dependent.
The detrimental effects of criminalization of vulnerable groups on HIV incidence and access to HIV prevention and treatment3,4 are widely acknowledged. The effects of such environmental factors on the continuity of HIV treatment have been less apparent. To date, the most commonly documented environmental barriers to ART effectiveness are those connected to interruptions of supply of antiretroviral treatment (stock outs) and characteristics related to models of HIV treatment delivery.5 Although incarceration as a cause of interruption of ART or methadone treatment has been previously documented,6,7 this study confirms the link between incarceration and ART failure in virologically stabilized patients.
Illicit drug use per se was not associated with viral rebound in this study, a finding that requires widening the analytical frame beyond the usual focus on individual behavior and biological markers to the broader causes of ART interruptions and treatment failure among PWUD. For sex workers who use drugs, violence by clients and police harassment are known to be risk factors for HIV acquisition and nonadherence to ART,8–10 with law enforcement crackdowns moving at-risk individuals to hidden or dangerous locations and undermining daily routines critical to antiretroviral treatment intake. The negative effects of violence by police and clients of sex workers may be mutually reinforcing: an earlier Vancouver study showed those sex workers who had experienced violence at the hands of the police to be 3 times more likely to experience client-perpetrated violence and twice as likely to experience client-perpetrated rape.11 In a recent study among injecting drug users in Odessa, Ukraine, police beatings were associated with sharply increased risk of HIV acquisition.4 This study by Milloy et al reminds us that police practices may also be tied to failures of HIV treatment.
Incarceration represents a major “biographic split” in the lives of people living with HIV to the detriment of those on antiretroviral therapy. Reduced access to ART11 and forced “treatment interruption”12 are frequent for individuals living in countries where vulnerable groups are criminalized.12,13 Even for those prisoners who eventually receive treatment, length of treatment interruptions may increase prisoner risk of developing antiretroviral resistance.14 With condoms unavailable in many penal settings, coinfection with sexually transmitted diseases may also increase HIV viral load,15 contributing to virological rebound in this population.
A common public health strategy is to recast hazard ratios in terms of attributable risk: that is, the fraction of events preventable by eliminating the exposure in question. In this study, the results show that the point and interval estimate of the hazard ratio is 1.83 (1.33–2.52) for recent incarceration. In other words, the attributable fraction for individuals exposed to recent incarceration is 40.0 (17.2–56.8) (estimate provided by Milloy et al for this editorial). This means that among the recently incarcerated IDUs, 40% of cases where viral load rebounded would be eliminated through an approach other than incarceration. If the lower bound of the interval is used, elimination of incarceration might at least have averted around one-fourth of viral rebounds. Analysis of attributable benefit is also possible, with methadone treatment in this study preventing as many as approximately one-fifth of cases of virological rebound. These are findings with major economic and policy implications. The need for more effective and cost-effective approaches is particularly acute in the many countries where PWUD are imprisoned for drug use or possession of drugs for personal use even in the absence of any other crime and in an economic climate where budget difficulties sharply constrain HIV treatment.
Overall incidence of viral rebound in this study (approximately 13% per year) is comparable to that reported among injecting drug users by Mocroft et al,16 where viral load rebounded after initial suppression in approximately 9% of patients. These findings by Milloy et al, however, suggest new directions for the interpretation of such percentages and underscore the importance of reexamination of multicohort analyses that have focused primarily on whether individuals used drugs and other individual determinants of HIV treatment outcomes. Share of PWUD incarcerated and experiences of police violence or harassment are only 2 of what should be a robust set of indicators used to characterize policy and health system elements critical to positive HIV treatment outcomes among PWUD. Others might include availability or lack thereof of opiate substitution treatment at HIV and tuberculosis treatment centers, police harassment of methadone or buprenorphine patients and providers, collateral fees required to access either ART or opiate substitution treatment, and presence of policies that implicitly or explicitly ban ART or tuberculosis treatment for those unable or unwilling to abstain from illicit drug use.
It is indeed time to start a new ART era, one in which research becomes more helpful in identifying structural and policy changes needed to help health staff and patients achieve optimal HIV treatment. This study by Milloy et al gives us an important lesson about how such research can be done.
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