JAIDS Journal of Acquired Immune Deficiency Syndromes:
Drug Treatment as HIV Prevention: A Research Update
Metzger, David S PhD*; Woody, George E PhD†; O'Brien, Charles P MD, PhD†
From the *HIV/AIDS Prevention Research Division and the †Treatment Research Institute, University of Pennsylvania, Philadelphia, PA.
This work was supported in part by the following research grants: P60-DA-005186-22, Center for Research on Improving the Treatment of Drug Abuse; U10-DA013043-07, Delaware Valley Node of the Clinical Trials Network (CTN); U01-AI-048014, Penn Prevention Clinical Trials Unit (PPCTU); and R01-DA-026344-01A1.
Correspondence to: David S. Metzger, PhD, University of Pennsylvania, HIV/AIDS Prevention Research Division, 3535 Market Street, Suite 4000, Philadelphia, PA 19104 (e-mail: email@example.com).
Drug use continues to be a major factor fueling the global epidemic of HIV infection. This article reviews the current literature on the ability of drug treatment programs to reduce HIV transmission among injection and noninjection drug users. Most data come from research on the treatment of opiate dependence and provide strong evidence on the effectiveness of medication-assisted treatment for reducing the frequency of drug use, risk behaviors, and HIV infections. This has been a consistent finding since the epidemic began among diverse populations and cultural settings. Use of medications other than methadone (such as buprenorphine/naloxone and naltrexone) has increased in recent years with promising data on their effectiveness as HIV prevention and as new treatment options for communities heavily affected by opiate use and HIV infection. However, few treatment interventions for stimulant abuse and dependence have shown efficacy in reducing HIV risk. The cumulative literature provides strong support of drug treatment programs for improving access and adherence to antiretroviral treatment. Drug users in substance abuse treatment are significantly more likely to achieve sustained viral suppression, making viral transmission less likely. Although there are challenges to implementing drug treatment programs for maximum impact, the scientific literature leaves no doubt about the effectiveness of drug treatment as an HIV prevention strategy.
In 1981 an outbreak of “community-acquired” Pneumocystis carinii was reported among 15 young men; seven were drug abusers, six were men who had sex with other men (MSM), and two were both drug users and MSM.1 This was one of the first published reports of cases that would later be classified as AIDS. It was a time of heightened concern throughout the medical community and those at risk and, increasingly, the general public. Although there was evidence of the connection between substance use and HIV, little was known then about drug users not in treatment, their injection and sexual risk practices, and more broadly, the impact of drug use on the nation's public health. Researchers and clinicians working with drug users rarely asked about sexual behaviors or syringe-related practices that could transmit bloodborne pathogens, and there was little public support for drug treatment programs or attention to any links between drug use and public health. Researchers, treatment professionals, and public health agencies were unprepared to respond to the sudden epidemic of HIV among drug users and their sexual partners.2
Nearly three decades later, estimates suggest that the global AIDS epidemic has begun to stabilize with over 33,000,000 people living with HIV and approximately equal numbers of new infections and deaths.3,4 Outside of sub-Saharan Africa, an estimated 10% of all new infections are attributed to injection drug use (IDU) despite significant regional variations. According to the Joint United Nations Program on HIV/AIDS, IDU is responsible for more than 80% of all HIV infections in eastern Europe and central Asia. The epidemic in countries in the Middle East and North Africa have been largely attributed to IDU, and it is currently linked to the growing epidemic in Indonesia, Vietnam, and Malaysia.5
The role of noninjection substance use (non-IDU) to the HIV/AIDS epidemic is also important. Although the risk of sexual HIV transmission is well known for non-IDU sex partners of IDUs, research has shown that among heterosexuals, alcohol and noninjection drug use are consistent predictors of HIV risks and new infections.6-8 Among MSM, substance use is more prevalent compared with the general population and is a known risk factor for HIV infection.9 In cross-sectional studies of MSM, alcohol and stimulant use are both associated with HIV risk and prevalence, whereas in prospective studies, substance abuse is consistently found to be a powerful predictor of new infections.10,11 Among the 4295 MSM who participated in Project Explore, the largest intervention trial ever conducted among HIV-negative MSM, drug and alcohol use before sex was a stronger predictor of incident infections than was unprotected receptive anal intercourse with a partner of unknown HIV status.12,13 Despite widespread awareness of the role of noninjection substance use in HIV sexual transmission, most of the scientific literature on drug treatment as HIV prevention focuses on IDU.
Methadone Treatment as HIV Prevention
The research literature of the past 25 years substantiates that methadone treatment is an effective HIV prevention intervention. Patients in methadone treatment use opiates significantly less often compared with those not in treatment.14-19 They also use significantly less while in treatment compared with what they were using pre- and posttreatment.17,20-22 Lower rates of opiate use have been found in patients who regularly attend methadone programs compared with those with poor attendance and among patients in methadone treatment regardless of whether they also received standard methadone maintenance services or intensive services at twice the cost.23-26
Consistent with the observed reductions in opiate use, available data suggest that methadone patients will have 40% to 60% fewer instances of opiate injection and needle-sharing events compared with those not in treatment. This association has been reported in studies using cross-sectional, prospective, and retrospective designs to compare methadone patients with heroin users not in drug treatment and in those assessing changes in cohorts of methadone patients during drug treatment.20,21,25,27-30 Research has also shown that rates of injection among patients who remain in treatment are significantly lower than those among patients who leave treatment.22,31
Perhaps most important from the perspective of public health, strong associations have been reported for methadone participation and lower rates of HIV prevalence and incidence. Heroin users who remain in methadone treatment during periods of rapid HIV transmission in their surrounding communities have a dramatically lower prevalence of infection compared with those who do not.32 HIV prevalence rates are also correlated with length of time in treatment. Both prospective and retrospective studies have shown that the incidence of HIV infections is significantly and inversely associated with patient participation in and the duration of methadone treatment.19,22,26,33,34
With few exceptions, studies conducted in the United States, Australia, Europe, and, more recently Asia have demonstrated significant associations between participation in methadone treatment and reductions in the frequency of opiate use in numbers of injections and injection-related risk behaviors and in the prevalence and incidence of HIV. Although there have been no randomized controlled trials (primarily in light of ethical concerns over the random assignment of individuals to treatments that do not include methadone modalities or to nontreatment controls), the cumulative results of these observational and case-controlled studies demonstrate the strong relationship between methadone treatment and protection from HIV infection.18,35-40
The implications of these findings are borne out in the expanded use of methadone maintenance treatment as a HIV prevention intervention. Its introduction is notable in Asia, where the dual epidemics of HIV and drug abuse began in the 1990s.41 The enormous investment by China in establishing a national methadone treatment system is a clear example of this “data-based” policy response. Before 2004, methadone treatment was limited to a few private clinics and was primarily used for detoxification. Today, there are more than 700 clinics treating upward of 160,000 patients. The methadone maintenance treatment system in China is the largest single drug treatment system in the world and data are just now becoming available on its treatment effects and impact on HIV/AIDS.42
Despite these impressive data, methadone treatment alone is not enough to end the global epidemic. Methadone treatment only works for opiate users and, even then, only for those who have consistent access to a methadone treatment program. In addition, the epidemic continues to change as evident in the increasing rates of HIV among non-IDU by sexual transmission.
Buprenorphine as HIV Prevention
Buprenorphine and the combination of buprenorphine-naloxone (Suboxone; Reckitt Benckiser Pharmaceuticals Inc., Warren, NY) are the most significant developments for opiate dependence treatment in years. Buprenorphine, a relatively safe and effective partial agonist, offers a new treatment option for opiate-dependent individuals, particularly in the United States, because primary care providers can prescribe it from the office setting, away from the highly regulated methadone treatment system.43,44 Recent reports on buprenorphine as HIV prevention show significant reductions in risk behaviors among adults and adolescents who receive the medication through both office- and clinic-based practices, consistent with reports on methadone maintenance treatment.43,45-48 The public health impact of buprenorphine and its combination with naloxone may as yet be limited given its higher cost per daily dose compared with methadone, although studies of its cost-effectiveness suggest that it compares favorably with methadone.49,50 A randomized double-blind trial among heroin injectors in Malaysia found significantly fewer risk behaviors and longer treatment stays in those assigned to buprenorphine compared with those assigned to naltrexone or placebo.51
Naltrexone as HIV Prevention
The opiate antagonist naltexone has been available for many years as a daily treatment for opiate dependence, but its impact has been limited by low levels of patient acceptability. As a result, little is known about its potential as HIV prevention. There are, however, many locations in the United States and around the world that might benefit from naltrexone as a treatment option to methadone or buprenorphine for opiate dependence. The most significant of these is the Russian Federation, where agonist treatments for opiate dependence are illegal but where HIV/AIDS is rapidly spreading among IDUs and, increasingly, among the sex partners of IDUs. The largest study to examine the impact of naltrexone on drug use and HIV in Russia was conducted in St Petersburg with 280 opiate-dependent participants enrolled into a double-blind four-group trial. Participants were randomized to naltrexone and fluoxetine; naltrexone and fluoxetine placebo; fluoxetine and naltrexone placebo; or double placebo.52 There were no significant effects for fluoxetine, but both naltrexone groups significantly reduced their opiate (heroin) use and HIV risk behaviors and remained in treatment longer compared with those receiving the naltrexone placebo.
Drug Treatment, Access to HIV Care, and Adherence
Research on drug treatment as HIV prevention has focused on the impact of treatment participation on the frequency of drug use and related behaviors, including injecting and sharing syringes, rinse water, and cotton. For HIV-infected drug users, accessing drug treatment can link them to HIV testing, antiretroviral treatment (ART), and HIV care.53-55 Not only are risk behaviors lower among patients in HIV care, but sustained reductions in viral load are achieved by the majority of adherent patients, regardless of mode of initial infection.56 Despite the personal and public health benefits of ART, active drug use can limit access to ART, reduce adherence among those on ART, and ultimately lead to increased morbidity and poorer health outcomes.57,58 By contrast, HIV-infected drug users participating in methadone treatment have been shown to have more rapid entry into ART treatment59 and significantly higher rates of ART adherence.60,61
The relationship among drug use, treatment participation, and ART adherence was more clearly defined in a retrospective analysis of 1558 visits accrued among a cohort of 276 HIV-positive IDUs in France.62 Regardless of their treatment participation, the IDUs who continued to inject had significantly poorer outcomes. Those in methadone or buprenorphine maintenance and not injecting were no different in measures of ART adherence to patients who had no history of drug use. However, ART adherence among those who continued to inject was two to three times worse regardless of drug treatment participation. This was the first study to document that drug treatment participation while actively injecting is insufficient for achieving ART adherence.62 Importantly, this same study found that retention in drug treatment is a significant predictor of long-term virologic suppression.63 These data are consistent with other research linking low ART adherence in the setting of active drug use and improved adherence among those who enter and remain in drug treatment.64
Drug Treatment and Sexual Risk Reduction
Risky sexual behaviors often co-occur with drug use, particularly in the setting of cocaine and other stimulant use.65-67 Few studies have found that participation in drug treatment is associated with reductions in sexual risk behaviors, and generally, interventions to reduce sexual risks among drug users have had poor results or at least have not differed from basic educational intervention approaches.67 However, more positive findings have emerged from studies of sexual risk reduction interventions that are delivered within the drug treatment program setting with the drug treatment program as the platform for intervention delivery. Findings have thus far held for both individual and group sessions as well as for gender-specific and gender-mixed,68-70 yet these results are less consistent than those on the effects of drug treatment on reducing injection-related risks.71,72 Effective approaches for reducing sexual risk behaviors have been and continue to be elusive, possibly attributable in part to the link between sexual risk behaviors and stimulant use and the absence of effective medication assisted treatments for stimulant use.
Drug Treatment and HIV Testing
HIV testing is a major part of effective HIV prevention and an essential component of the “seek, test, treat, and retain in care” approach.73,74 Because drug users are at elevated risk of HIV infection, drug treatment programs would seem to be on the “front lines” of efforts to identify individuals infected but unaware of their status. Despite this, research has found few drug treatment programs that actually provide HIV testing to their clients,75,76 a situation that, at minimum, is cost-inefficient and at most is a lost opportunity to engage persons at high risk for testing and counseling and referrals of positives to HIV treatment and care.
Since the relationship between drug use and AIDS was first identified, drug users have been the focus of numerous interventions to prevent HIV transmission but none have received as much attention as substance abuse treatment. The cumulative science has shown that drug treatment reduces drug use, related risk behaviors, and the acquisition and transmission of HIV and other bloodborne pathogens. Most of these findings are from countries that have made drug treatment available for drug addiction for years, but recent evidence is emerging in countries that have newly established treatment programs and systems. The relationship between drug treatment and HIV prevention is consistent over time and across cultural settings, serving to underscore that, like with other chronic diseases, drug abuse and dependence is a chronic medical condition that can be treated with effective, therapeutic approaches. This is particularly the case for opiate dependence with such opiate substitution therapies as methadone, buprenorphine/naloxone, and naltrexone now available. Unfortunately, there are as yet no comparably effective medication-assisted treatments for cocaine and other stimulant use. Although treatment strategies that do not use medications have shown some evidence of efficacy among high-risk stimulant users, the development of a safe and effective treatment medication for stimulant abuse and dependence remains a high priority.
Drug treatment can prevent HIV and it can do much more; drug treatment programs that provide access to ART for HIV-infected patients also have improved adherence to those treatments. Studies have shown that it is the impact of drug treatment on current use of substances that helps to improve ART adherence, not past diagnoses or individual characteristics. Despite this, there are few drug treatment programs that offer HIV testing and counseling to their patients, a situation that directly conflicts with global prevention initiatives and warrants public health action. Research also suggests that methadone maintenance programs have potential for providing directly observed treatment and contingency management interventions to improve ART adherence among HIV-infected patients, a promising development in need of future research and program development.60,77,78
Drug treatment is HIV prevention in many countries around the world, yet the vast majority of drug users do not have access to effective substance abuse treatments, even in countries that have long been considered developed.79 Public health policies should promote the potentials of drug treatment to manage drug addiction and prevent the spread of HIV and other bloodborne diseases. As a minimum, all drug treatment programs should routinely offer HIV testing and counseling and referrals for HIV treatment to their patients. Although there are challenges to implementing drug treatment programs for maximum impact, the scientific literature leaves no doubt about the effectiveness of drug treatment as an HIV prevention strategy.
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drug treatment; drug treatment programs; prevention; treatment as HIV prevention
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