AIDS was first observed in injecting drug users (IDUs) in late 1981.1 The antibody test for the AIDS virus was developed in 1984–5, and early testing showed very high seroprevalence—30% or greater—among IDUs in several areas, including New York City,2 Edinburgh3 4 and Amsterdam.5 These findings led to a considerable amount of research on HIV/AIDS among IDUs, and this research has been quite successful in identifying methods for reducing HIV transmission among IDUs. Yet, it is also clear that, worldwide, the problem of HIV infection among IDUs is as great or greater now as it was in the early 1980s, and an additional problem of drug use-facilitated sexual transmission of HIV has developed.

In this article, we will outline what we believe are important items for a research agenda on psychoactive drug use and HIV prevention. We do not intend this agenda to be comprehensive. Rather we see it as complementary to other recently proposed research agendas for HIV prevention research.6^–8 We will discuss four major research topics: (1) why evidence-based effective prevention programmes have not been implemented, (2) HIV infection among ethnic minority drug users, (3) relationships—or lack of relationships—between individual risk behaviour and HIV infection and (4) reducing drug-use-related sexual transmission of HIV and other sexually transmitted infections (STIs). These topics were selected because we see them as critical for reducing HIV transmission among drug users (topics 1 and 4), reducing health disparities among racial and ethnic groups of drug users (topic 2), and understanding HIV epidemiology and evaluating prevention programmes for drug users (topic 3).

FAILURE TO IMPLEMENT EVIDENCE-BASED PREVENTION PROGRAMMES

Programmes such as community outreach to IDUs and providing good access to sterile injection equipment proved remarkably effective in reducing HIV transmission among IDUs. If such programmes are begun when HIV prevalence is low in a population of IDUs, it is possible to keep prevalence at a low level indefinitely.9^–11 Even if these programmes are not implemented until after prevalence has reached high levels, it is still possible to limit HIV transmission greatly and to “reverse” HIV epidemics among IDUs.12

The studies demonstrating the effectiveness of HIV prevention for IDUs should have provided sufficient evidence for actions to control HIV among IDUs worldwide. Unfortunately, this has not been the case. HIV is spreading rapidly among IDUs in many areas of Eastern Europe and Asia. WHO/UNAIDS estimate that, outside of sub-Saharan Africa, approximately one-third of all new cases of HIV infection are among injecting drug users.13

Understanding why effective HIV prevention programmes have not been implemented on the scale that is needed—and how this can be remedied—is probably the most important question for research on HIV prevention for IDUs. The problem is particularly important in low- and middle-income countries,14 which are currently experiencing the greatest spread of HIV among IDUs.13

Although there are many contributing factors to this lack of implementation, the stigmatisation of IDUs is undoubtedly a major factor in almost all geographic areas.15 There may be very important limits on attempting to reduce the stigmatisation of drug users through rational persuasion—presentation of factual information about the needs for, the effectiveness of, and the lack of negative consequences of HIV prevention programmes for IDUs. Recent studies indicate that stigmatisation of groups such as drug addicts is not simply a matter of a lack of information about others, but involves different mental processes. Harris and Fiske16 found that while the medial frontal cortex was activated in thinking about social groups in general, it was not activated in thinking about “extreme out-groups” such as drug addicts. This was interpreted as the subjects showing a “disgust” reaction to addicts and “dehumanising” addicts.

Stigmatisation of illicit drug use, particularly illicit injecting drug use, is incorporated into international treaties, national and local laws, and the popular cultures of most countries (including high-, middle- and low-income countries). Thus, reducing stigmatisation of illicit injecting drug use is likely to be a difficult task. It is important to note that implementing effective HIV prevention programmes for IDUs requires a nuanced reduction of stigmatisation of injecting drug use. IDUs need to be presented as beings who deserve access to the means to protect themselves from HIV (access to sterile injection equipment, drug abuse treatment and condoms), and from AIDS (access to anti-retroviral treatment), but policies probably should not attempt to create full social approval of illicit drug use. Indeed, the charge that implementing HIV prevention programmes “condone” heroin and cocaine injection and will lead to “legalisation” of heroin and cocaine is one of the most common rationales cited by opponents of HIV prevention for IDUs. Needless to say, in no area where effective HIV prevention programmes have been implemented have heroin or cocaine been given the same legal and cultural status of drugs like alcohol and nicotine.

Although we clearly do not have an adequate understanding of how to overcome stigmatisation of illicit drug use, there have been a limited number of case studies of initiation of HIV prevention programmes for IDUs.17^–22 Spain and Brazil provide two strong examples of countries that have policies and interventions that address harm reduction and HIV prevention in a less stigmatised and stigmatising environment.23 24 In Spain use of drugs is not a criminal offence and is punishable only by fines and treatment referrals.25 Possession and use of drugs in public places in Spain is sanctioned by administrative measures. Furthermore, Spain has harm reduction programmes in prisons, including syringe exchange programmes.25 A recent study showing a sharp decrease in the number of new drug injectors in Spain between 1991 and 2004 suggests that needle exchange programmes have not promoted drug injection.26

Since 1996, the Ministry of Health of Brazil has guaranteed free and universal access to antiretroviral treatment for people living with HIV/AIDS.27 Of the 36 000 IDUs in low- and middle-income countries receiving antiretroviral therapy by the end of 2005, 30 000 were in Brazil, with the remaining 6000 dispersed over 45 countries.28 Key elements in the Brazilian response to the HIV/AIDS epidemic among IDUs include the administration of the Brazilian universal public health system, the provision of universal access to highly active antiretroviral therapy and the development of harm reduction projects that are politically and financially supported by the federal government.24 A recent global systematic review indicates that adherence to highly active antiretroviral therapy for HIV among HIV-positive drug users can be achieved and can be similar to rates reported for other people living with HIV/AIDS.29 This review indicates that better adherence (50–75%) is observed among drug users participating in comprehensive services that provide HIV and addiction treatment (eg, directly observed antiretroviral therapy for HIV, addiction substitution therapy), psychosocial support and case management.29 30

As the great majority of new HIV infections among IDUs are occurring in low- and middle-income countries, two additional aspects of overcoming stigmatisation and implementing HIV prevention programmes for IDUs are worth noting.

1 Developing local advocates

While outside (foreign) support for implementing HIV prevention for IDUs can be very helpful, it appears that it is necessary to have inside (local) advocates who can provide strong support for the programmes.31 32 (Note that “local” can refer to city, province or national levels, at whatever level the policy decisions are being made.) Without local advocates, efforts by “outsiders”, including donor agencies, are likely to be rejected. The local advocates need to have a strong commitment to HIV prevention, knowledge of the local policy system and legitimacy as actors within that system.

At present, we do not have any systematic research on how to promote the emergence of local advocates for HIV prevention for IDUs. Nor do we have any systematic data on the types of training that might be provided to local advocates to increase their effectiveness.

2 Scaling up HIV prevention programmes for IDUs

An important issue in HIV prevention for IDUs in low- and middle-income countries is taking the programmes to public health scale. Pilot projects do not stop HIV epidemics. The available resources, both financial and trained staff, may be quite limited and there is likely to be great urgency in implementing programmes on a public health scale. The question of “coverage”, the percentage of IDUs that need to be reached through HIV prevention programmes, has received more attention recently,33 but we are far from knowing how to determine the “best” combination of prevention programmes and the “best” coverage level for the different individual prevention programmes for any given geographic area.

The randomised clinical trial (RCT) is currently considered the “gold standard” method for conducting research on HIV prevention.34 The RCT is not, however, likely to be a particularly useful method for conducting research on how to initiate and then scale up HIV prevention for IDUs in low- and middle-income countries. Rather, the most productive methodology would probably be a systematic collection of detailed case histories of implementation of HIV prevention programmes for IDUs (including unpublished studies), and organisation of the data within a theoretical framework. We would suggest “diffusion of innovation”,35^–37 as a theoretical framework. Mathematical modelling38 and operations research should be particularly useful for addressing questions related to scaling up.

DISPARITIES IN HIV INFECTION AMONG ETHNIC MINORITY IDUS

While the sharing of needles and syringes among IDUs will clearly transmit HIV regardless of the ethnicity of those sharing, there is a common pattern of higher HIV infection among racial/ethnic minority IDUs (particularly, in the USA among African–American IDUs compared with white IDUs). Higher HIV prevalence has been observed among racial/ethnic minority IDUs in many studies in the USA.39^–49 These differences emerged very early in the HIV epidemic among IDUs in the USA, in the 1970s,50 51 and have persisted up to the present.52

The phenomenon of higher HIV prevalence among minority drug users, however, is decidedly not limited to the USA. Substantially higher HIV prevalence has been found among disadvantaged ethnic minority IDUs in many different areas of the world: First Nation IDUs in Canada,53 54 German IDUs in the Netherlands,55 Vietnamese IDUs in Australia,56 Roma IDUs in Eastern Europe,57 ethnic Russian IDUs in Estonia,58 “hill tribes” (Zhuang, Tay, Nung) IDUs in Southeast Asia,59 60 and Uighur IDUs in southwest China.61

While there is a clear pattern of higher HIV prevalence and incidence among ethnic minority IDUs in many different countries, there are some exceptions to the general rule of higher prevalence among ethnic minorities. Chawarski et al62 found lower HIV prevalence among ethnic Chinese IDUs than among ethnic Malay IDUs in Malaysia and Stachowiak et al63 found lower HIV prevalence among ethnic Russian IDUs than among ethnic Tajik IDUs in Tajikistan.

Higher HIV prevalence among ethnic minority IDUs can have multiple adverse effects. The combined stigma (injecting drug use, AIDS and ethnic minority status) can make public officials less likely to provide prevention and treatment services. Fear of discrimination can make ethnic minority group members less likely to utilise whatever services are available. This can lead to increased HIV transmission within the ethnic minority group and the community as a whole. There is also an increased probability that HIV infection among IDUs will lead to sustained heterosexual HIV transmission, within the ethnic minority group in particular, and also within the community as a whole.

The frequency at which higher rates of HIV infection have been observed among ethnic minority IDUs suggests that there are probably social structure factors underlying the phenomenon. The factors that might generate the initial differences and the factors that might sustain the differences over time, however, have not been identified.

INDIVIDUAL RISK BEHAVIOUR AND HIV INFECTION

One factor that does not explain the differences in HIV infection among ethnic minority versus ethnic majority IDUs is differences in the rates of individual risk behaviours. In none of the studies noted above did higher rates of risk behaviour explain the higher rates of HIV prevalence among ethnic minority IDUs. Indeed, ethnic minority IDUs often reported lower rates of risk behaviour. Individual-level risk behaviour differences also do not explain rates of HIV incidence across ethnic groups of IDUs.53 64^–66 In studies of HIV incidence among ethnic groups of IDUs, ethnicity is often a statistically significant predictor of incident infections after controlling for all measured risk behaviours. There are similar findings for sexual transmission (both among men who have sex with men (MSM) and heterosexuals) of HIV among African–Americans, who typically have higher HIV seroprevalence but report equal or lower levels of sexual risk behaviour than white MSM and white heterosexuals.67 68

There are, of course, many factors that may mask a simple positive correlation between rates of individual-level risk behaviour and group-level rates of HIV infection, including the numbers of potential HIV transmitters in different groups (and their stage of HIV infection), and risk network and mixing patterns, as well as social desirability bias in reporting of risk behaviours. Risk networks (both injecting and sexual) factors would seem to be the most likely potential explanation for the lack of strong relationships between individual behaviour and actual HIV infection. Still, the present difficulties in explaining important group differences in both HIV prevalence and incidence in terms of risk behaviours must be considered a major gap in our knowledge of HIV epidemiology. In particular, the lack of a well-understood relationship between individual-level differences in risk behaviour and group-level differences in HIV infection creates major problems in evaluating HIV prevention programmes. If a programme reduces risk behaviours among participants, do we have any certainty that the programme will also reduce HIV infection in groups of participants? Should prevention programmes that attempt to ameliorate disparities in HIV infection among racial/ethnic groups even target individual risk behaviours? Or should they first identify the network (or other) factors that generate and maintain the disparities and then target those factors?

Conducting research to clarify relationships between risk behaviours and HIV infection would not be a simple task. We would suggest that the appropriate first step would be a systematic review to identify examples of epidemiological conditions in which clear positive relationships exist between risk behaviour and HIV infection across subgroups and geographic areas. Such a review should also examine the potential importance of methodological factors among the various studies. Mathematical modelling might then be utilised to incorporate such factors as risk networks and background HIV prevalence. Measuring HIV prevalence is, of course, relatively easy. Measuring risk networks (eg, concurrent risk partners) so that one could estimate the effects of changes in risk behaviour on changes in HIV infection would be considerably more difficult, but would greatly increase our ability to evaluate HIV prevention programmes for drug users and other persons at elevated risk for HIV.

REDUCING SEXUAL RISK BEHAVIOUR AMONG INJECTING AND NON-IDUS

There are multiple potential linkages between psychoactive drug use and sexual transmission of HIV. First, people who have become infected with HIV through injecting drugs may then transmit the virus to non-injecting sexual partners. Rapid HIV transmission among IDUs has been followed by increases in heterosexual transmission of HIV in many countries.13 Non-injecting drug use may also facilitate sexual transmission of HIV through different mechanisms, including exchanging sex for drugs or money to purchase drugs, reduction of inhibitions, perceived increase in sexual pleasure, impaired decision-making while under the influence of drugs, and self-medication for sexual abuse and/or commercial sex work.69

Drug users are also at elevated risk for other STIs69 70 that may biologically facilitate HIV transmission. Herpes simplex virus-2 (HSV-2) may be the most common of these STIs.71 72 Unfortunately, two recent studies testing whether using acyclovir to suppress HSV-2 did not show any protection against HIV acquisition.73 74

A relatively large number of studies have evaluated individual and small group interventions to reduce sexual risk behaviour of injecting and non-IDUs. Although there are notable examples of intervention studies that reduced sexual risk behaviour among non-IDUs, for example Sterk et al75^–77 and Wechsberg,78 the overall pattern of results has not been encouraging. There have been three systematic reviews of interventions to reduce sexual risk behaviour among IDUs and non-IDUs. Copenhaver et al79 found that there was a net overall positive effect in reducing sexual risk, but that condom use declined over time. Semaan et al80 found a modest net overall effect, but the effect was due solely to studies in which no services were provided to the control group. A Cochrane Collaboration meta-analysis, which is the most recent review, contains the largest number of randomised clinical trials and includes studies conducted in low- and middle-income countries, found no positive effect for psychosocial interventions compared with the “standard” intervention provided to control participants.81

Different drugs have been associated with increased sexual transmission of HIV, particularly crack cocaine,82^–86 and more recently methamphetamine.87^–92 There are multiple possible mechanisms through which drug use may increase sexual transmission. Present interventions to reduce sexual risk behaviour among drug users appear to have only modest effectiveness. A primary question for future research is whether there are general principles for reducing drug-related sexual risk behaviours or whether effective interventions will need to be specific to the type of drug used, specific to the particular mechanism through which the drug increases sexual risk, and specific to the particular target population. Developing, testing and then implementing highly specific interventions would be a formidable task.

SUMMARY

AIDS was first observed among IDUs in 1981. Research studies very quickly identified programmes to reduce needle-borne transmission of HIV. HIV has, however, continued to spread among both injecting and non-injecting drug users, and we urgently need new research to address current problems in the field. The box summarises our proposed research agenda. We would note that a wide variety of research designs will be needed for these studies, and that the randomised controlled trial design would be appropriate for only a modest percentage of the studies. Thus, we would recommend that research funding agencies consider the variety of other applicable designs for these questions (see West et al34).