Daniel Wolfe

Treatment and care for injecting drug users with HIV infection: a review of barriers and ways forward

We review evidence for effectiveness, cost-effectiveness, and coverage of antiretroviral therapy (ART) for injecting drug users (IDUs) infected with HIV, with particular attention to low-income and middle-income countries. In these countries, nearly half (47%) of all IDUs infected with HIV are in five nations--China, Vietnam, Russia, Ukraine, and Malaysia. In all five countries, IDU access to ART is disproportionately low, and systemic and structural obstacles restrict treatment access. IDUs are 67% of cumulative HIV cases in these countries, but only 25% of those receiving ART. Integration of ART with opioid substitution and tuberculosis treatment, increased peer engagement in treatment delivery, and reform of harmful policies--including police use of drug-user registries, detention of drug users in centres offering no evidence-based treatment, and imprisonment for possession of drugs for personal use--are needed to improve ART coverage of IDUs.

Human rights and HIV prevention, treatment, and care for people who inject drugs: key principles and research needs.

Efforts to provide HIV prevention, treatment, and care to injecting drug users (IDU) are shaped by tensions between approaches that regard IDU as criminals and those regarding drug-dependent individuals as patients deserving treatment and human rights. Advocates for IDU health and human rights find common cause in urging greater attention to legal frameworks, the effects of police abuses, and the need for protections for particularly vulnerable populations including women and those in state custody. Arbitrary detention of drug users, and conditions of pretrial detention, offer examples of how HIV prevention and treatment are adversely impacted by human rights abuse. National commitments to universal access to prevention and treatment for injecting drug users, and the recognition that users of illicit substances do not forfeit their entitlement to health services or human dignity, offer a clear point of convergence for advocates for health and rights, and suggest directions for reform to increase availability of sterile injection equipment, opiate substitution treatment, and antiretroviral therapy. For IDU, protection of rights has particular urgency if universal access to HIV prevention and treatment is to become an achievable reality.

Concerns about injectable naltrexone for opioid dependence

In The Lancet, Evgeny Krupitsky and colleagues report on the use of injectable naltrexone for treatment of opioid dependence. Their report comes some months after the US Food and Drug Administration (FDA) approved use of the preparation for opioid-dependent patients on the basis of the same fi ndings. The study by Krupitsky and colleagues suggests the strong potential of a oncemonthly, extended-release formulation of injectable naltrexone for opioid addiction—the median proportion of weeks of confi rmed abstinence was 90·0% in the depot naltrexone group compared with 35·0% in the placebo group (treatment eff ect 55% [95% CI 15·9–76·1], p=0·0002). The study is also striking, however, for the questions it raises about the FDA’s approval processes and clinical trial ethics. Factors requiring scrutiny include paucity of effi cacy data, adequacy of risk assessment (particularly of overdose risk in treatment dropouts), and the questionable ethics of a placebo-controlled trial when an accepted standard of treatment exists. The FDA’s assessment of depot naltrexone’s effi cacy was based on then-unpublished evidence from this trial in Russia, in which 250 eligible patients at 13 sites were randomly assigned to receive 380 mg depot naltrexone or placebo. This single study, in which 54% of patients did not complete the protocol and just over half of those on naltrexone received the full treatment course, was judged suffi cient proof by the FDA. For evidence on safety, the FDA accepted data from the Russian study and another in the USA in patients with alcohol or opioid dependence, or both. Strikingly, neither the materials provided to the FDA advisory committee nor the Lancet study make clear what follow-up was done to evaluate post-treatment opioid overdose in the participants in the Russian trial. Data from the US study are similarly vague on post-treatment adverse events. The FDA sometimes requires only a single clinical trial for new indications of an already approved drug. A single trial is not justifi ed, however, when there are questions about the safety of the drug as it will be prescribed or recommended. Although voluntary reporting captures only a small portion of serious adverse events that occur once a drug enters the marketplace, approval of depot naltrexone for alcoholism treatment has been followed by reports to the manufacturer of 19 fatalities, some necessary before a patient could be started on treatment for multidrug-resistant tuberculosis, which is longer, more expensive, more toxic, and less eff ective than is fi rst-line therapy. Thus strengthening and scale-up of laboratory capacity needs to go hand-in-hand with implementation of the MTB/RIF test. Finally, scaling up of testing needs to be accompanied by a rapid increase in access to treatment. In the past decade, about 5 million people developed drug-resistant tuberculosis but less than 1% had access to appropriate treatment, and 1·5 million died. The positive results with the MTB/RIF test are an urgent wake-up call to the international community that a substantial increase in capacity to manage multidrug-resistant tuberculosis at scale is needed, together with major improvements in the availability of high-quality aff ordable treatment.

HIV in Central Asia: Tajikistan, Uzbekistan and Kyrgyzstan

The Central Asian Republics of Tajikistan, Kyrgyzstan and Uzbekistan varyin size, gross national product, social and political organization, and ethniccomposition. Nonetheless, a number of factors argue for their inclusion in asingle chapter on Central Asian responses to HIV. The territories of the threecountries overlap, with national borders originally demarcated under Stalininterlocking like a jigsaw puzzle. All three of the republics experienced dis-ruption of social supports in general and health care financing in particular

Lives to save: PEPFAR, HIV, and injecting drug use in Africa.

This article focuses on US Presidents Emergency Plan for AIDS Relief (PEPFAR) programme and the need for it to reach thousands of injecting drug users in PEPFAR countries in Africa many of whom have HIV. It states that the silver lining of Africa’s growing injection-driven HIV epidemic is that the measures that can stop it are cost effective well researched and easily brought to scale. Additionally PEPFAR has the rare opportunity to save many lives in Africa by the encouragement and funding of effective strategies for HIV prevention and treatment for drug users.

Harm reduction and human rights: finding common cause

Early struggles against forced testing and quarantine of people with HIV in the United States, the use of the courts to advance access to antiretroviral treatment in South Africa, and the defence of detained HIVactivists in China all testify to the power of human rights advocacy in the service of public health. The growing crisis of HIV infection through injection drug use, now estimated to account for nearly one-third of new HIV infections outside sub-Saharan Africa, poses a similarly promising area for collaboration between human rights advocates and those seeking to deliver HIV services to injecting drug users. Such services have been growing since the 1990s, particularly in countries of eastern Europe, the former Soviet Union and Asia, where sharing of contaminated needles accounts for the overwhelming majority of new HIV infections. Wherever efforts to treat and prevent HIVamong injecting drug users exist, public health practitioners encounter a familiar problem: the deep social marginalization of their target populations, in this case compounded by the hypercriminalization of drug use and the widespread violation of drug users’ rights by law enforcement and other officials.

Progress or backsliding on HIV and illicit drugs in 2008

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POLITICAL AND SYSTEMIC BARRIERS INCREASING RISK OF HIV FOR INJECTING DRUG USERS IN EAST AFRICA

The practice of flashblood, injecting the blood of other heroin users to relieve withdrawal symptoms documented by McCurdy et al. (June 2010) [1], underscores not only the risk of human immunodeficiency virus (HIV) transmission among injecting drug users in East Africa, but also the urgent need for effective opiate substitution treatment. Tanzania is alone in the region in its initiation of methadone treatment for opiate dependence, but the targets for this pilot effort remain far below estimates of need [2]. Despite widespread needle sharing and HIV transmission among injecting drug users (IDUs) on the coast and in Nairobi, the Kenyan National Campaign Against Drugs Abuse Authority (NACADA) has raised concerns that needle exchange contradicts official government policy of ‘total abstinence and a drug free lifestyle’, and noted publicly that the ‘benefits of methadone are far outweighed by the risks’ and that Kenya is ‘not in a position to handle methadone substitution therapy’ [3]. Sterile syringe programs remain unavailable anywhere in Africa except Mauritius [4]. The US President’s Emergency Plan for AIDS Relief (PEPFAR) is legally required to collect data on IDUs assisted by its programs [5, p. 38], and the United States no longer bans federal support for needle exchange programs. Nonetheless, PEPFAR—which supports the Tanzanian methadone pilot—has yet to fund harm reduction measures such as needle exchange and methadone treatment that have been rigorously demonstrated to be effective in HIV prevention [6]. Qualitative research of the kind proposed by McCurdy and colleagues on those factors, including flashblood, that increase the vulnerability of women IDUs is indeed important. Similar analysis of the political and structural dynamics shaping the risk environment in East Africa may be equally critical if the aim is removing barriers to effective HIV prevention and treatment.

Reconceptualizing research on HIV treatment outcomes among criminalized groups.

Milloy et al make 1 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, 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 treatment 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. Although incarceration as a cause of interruption of ART or methadone treatment has been previously documented, 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, 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. In a recent study among injecting drug users in Odessa, Ukraine, police beatings were associated with sharply increased risk of HIV acquisition. 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 ART and forced “treatment interruption” are frequent for individuals living in countries where vulnerable groups are criminalized. Even for those prisoners who eventually receive treatment, length of treatment interruptions may increase prisoner risk of developing antiretroviral resistance. With condoms unavailable in many penal settings, coinfection with sexually transmitted diseases may also increase HIV viral load, 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

Injectable extended-release naltrexone for opioid dependence – Authors' reply

Open Society Foundations, International Harm Reduction Development Program, New York, NY 10019, USA (DW); INSERM, U912 (SE4S) Marseille, France; ORS PACA, Marseille, France (MPC); Université Aix Marseille, IRD, Marseille, France (MPC); Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA (ND); Yale University AIDS Programme, New Haven, CT, USA (DB); and Alcohol and Drug Service, St Vincent’s Hospital, Darlinghurst, NSW, Australia (AW)