Commentaries HIV Prevention Research: Accomplishments and Challenges for the Third Decade of AIDS A B S T R A C T The past 2 decades have taught us that HIV prevention can work. We now have evidence from places as diverse as Senegal, Thailand, Uganda, and Australia that concerted HIV prevention efforts at the national level have resulted in the maintenance of low seroprevalence rates where they otherwise would have been expected to rise. We are beginning to observe declining rates of HIV prevalence and incidence in places and populations with historically high rates—for example, injection drug users in New York City. This trend points to the long-term impact of prevention efforts in those communities.1,2 The best of these efforts have been based on sound scientific research. As we move into the third decade of the AIDS epidemic, it is important to restate principles, acknowledge advances, and identify challenges and future directions in HIV prevention research. (Am J Public Health. 2000;90: 1029–1032)
Judith D. Auerbach, PhD, and Thomas J. Coates, PhD HIV/AIDS is a complex biological, behavioral, and social phenomenon, and the science of its prevention requires a complex strategy, governed by a number of specific principles. HIV prevention science must be comprehensive and multidisciplinary, integrating biological, behavioral, and social science approaches and methods; include both basic and intervention research; focus on primary prevention, but also address secondary prevention; be driven by the epidemiology of HIV/AIDS and the state of scientific knowledge; simultaneously consider population, mode of transmission, and level of social unit (i.e., individual, family, social network, organization, etc.) targeted; have both a domestic and an international orientation; and have public health utility and applicability.
Advances in HIV Prevention Intervention Science We characterize exemplary HIV prevention interventions in terms of their strategic focus: enhancing access to prevention technologies, providing appropriate prevention counseling and education, changing social norms and policies to promote prevention, and employing medical strategies, such as therapeutic agents, for HIV prevention.
Counseling Strategies Individual or small-group counseling about condom negotiation and use within sexual relationships, sometimes combined with sexually transmitted disease (STD) or HIV testing and diagnosis, can reduce risk for HIV or STD transmission. Both brief and multisession interventions have been efficacious in reducing risk behaviors and recurrent STDs among men and women in STD clinics and in primary care clinics in the United States.5,6 Voluntary counseling and testing interventions focused on couples have reduced sexual risk behaviors with both primary and nonprimary partners in Kenya, Tanzania, and Trinidad.7
Social Strategies The risk and protective behaviors of individuals are affected by the social norms and policy environments governing their communities. Interventions that address social network and community-level phenomena have been effective in reducing HIV risk among a range of population groups in different geographic settings. The “Mpowerment” project, for example, is a communityrandomized, peer-led intervention for young gay men. Now replicated in a number of cities, it focuses on community building and
Access People cannot take protective actions unless they have access to protective devices and services. Improved access to condoms among sexually active high school students has resulted in greater use of condoms during last intercourse.3 Similarly, access to sterile needles and syringes through needle and syringe exchange programs has resulted in decreased needle sharing and other drug use– related HIV risk behaviors among injection drug users.2,4 July 2000, Vol. 90, No. 7
Judith D. Auerbach is with the Office of AIDS Research, National Institutes of Health, Bethesda, Md. Thomas J. Coates is with the AIDS Research Institute and Center for AIDS Prevention Studies, University of California, San Francisco. Requests for reprints should be sent to Judith D. Auerbach, PhD, Office of AIDS Research, NIH Building 2, Room 4E30, 2 Center Dr, Bethesda, MD 20892 (e-mail:
[email protected]). This commentary was accepted April 3, 2000. Note. The views expressed are those of the authors and do not reflect the position of the National Institutes of Health or any other federal agency.
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social support and has resulted in reduced levels of unprotected anal intercourse among intervention community participants compared with those in control communities.8,9 Other network and community-level interventions among drug users, gay men, women with low income, and military recruits have focused on enlisting peer, team, and opinion leaders to train them in how to communicate, encourage, and reinforce health-protective messages. Randomized trials of such interventions have demonstrated significant decreases in risk behaviors, as well as in STD and HIV incidence.10–14 Media campaigns to promote and normalize condom use through intensive social marketing have been successful at the community level. In Zaire, for example, condom sales increased from fewer than 1 million per year in 1987 to more than 18 million in 1991 after widespread social marketing of condoms.15 Similarly, the nationwide HIV prevention campaign initiated by the Swiss government in 1987 included the promotion of condoms in nonmonogamous relationships, with the result that condom use with nonprimary partners has increased steadily in all age groups, even while the number of reported sex partners has not.16 Policy interventions also can effectively change social norms and behaviors to promote HIV prevention at the aggregate level. One of the best examples is the 100% Condom Program initiated by the government of Thailand in 1990, which made condom use mandatory in all brothels. The policy, which was implemented through a partnership between brothel owners, police, and public health clinics, resulted in a 90% increase in consistent condom use and a 75% decrease in STDs among sex workers. Moreover, the prevalence of HIV infection among military recruits, who frequent brothels, declined from about 11% before the policy change was enacted to 6.7% afterward.17,18
probability of transmission, even when viral load was high. In fact, no uninfected male partner of an infected female acquired HIV if he was circumcised.23 Thus, there is now a debate about whether circumcision can and should be recommended as a medical strategy for HIV prevention.24,25 Antiretrovirals for vertical transmission. HIV transmission from mother to child is now highly controlled in many parts of the world through antiretrovirals administered to the mother and infant prior to, during, and after delivery. This strategy was proven effective under different scenarios with azidothymidine/zidovudine (AZT/ZVD) and nevirapine.26–28 However, the risk of transmission during breastfeeding remains, and this has led to the important question of whether or not to recommend against breastfeeding in developing countries—a decision that has significant cultural as well as public health implications.29 Antiretrovirals for postexposure prophylaxis. An emerging medical strategy for HIV prevention is postexposure prophylaxis with state-of-the-art antiretrovirals following sexual or parenteral exposure. This strategy is an extension of the prophylactic use of antiretrovirals as the standard of care for health care workers exposed to HIV in the context of their work. A recent study in San Francisco demonstrated the overall feasibility of extending postexposure prophylaxis to nonoccupational exposures, but it also raised a number of questions, particularly about the role of the source (HIV-infected) partner.30,31
Challenges in HIV Prevention Research The advances noted above point to some of the current and future challenges in HIV prevention research. These fall into 3 somewhat overlapping categories: scientific, political and cultural, and ethical.
Medical Strategies Scientific Challenges Treatment of STDs. Given the added susceptibility to HIV infection brought about by the presence of certain other STDs, one approach is to treat STDs in the hope that this will reduce HIV transmission. This has been tested under 2 different scenarios—mass vs syndromic treatment in Rakai, Uganda, and in Mwanza, Tanzania, respectively. Unfortunately, these trials produced somewhat contradictory and equivocal results (for both HIV and other STDs), leaving some to propose a hybrid approach that uses elements of both strategies as the next step.19–22 Male circumcision. In the Rakai STD trial, male circumcision was linked to low 1030
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Methodological challenges. First and foremost, it remains difficult (and undesirable) to directly observe and measure HIV risk and protective behaviors related to sex and drug use, because they are private and, sometimes, illicit. Second, because these behavioral phenomena cannot be observed directly, HIV prevention science relies on indirect measures to a great extent. A lack of consensus continues among the prevention science community about the relative validity of such measures, particularly selfreport vs biological markers such as incident STDs.
Third, there is a lack of consensus about whether randomized, controlled trials are the only design that can produce real measures of efficacy of HIV prevention interventions. Given the difficulties of conducting behavioral or biomedical intervention trials with HIV incidence outcomes (owing to low HIV prevalence rates that require large sample sizes and sufficient power to detect real intervention effects, standards for control conditions that require active HIV prevention counseling, etc.), the randomized trial may be too elusive a “gold standard” of evidence. In addition, some argue that the randomized trial is not the appropriate strategy for evaluating the complex social phenomena required to bring down rates of HIV transmission. Fourth, most HIV prevention interventions have been tested and implemented in small-scale studies in only 1 or 2 population groups, and their replicability and generalizability are yet to be demonstrated. Similarly, these studies typically follow participants only for short periods of time postintervention. The durability of intervention effects is not well known. Finally, with respect to methodological issues, there is still much room for improvement in recruitment, retention, and adherence in prevention trials. Of the problematic aspects of many prevention intervention studies involving underserved populations in particular (e.g., drug users, the homeless, and/or mentally ill persons), one of the most troubling is the significant rates of attrition and loss to follow-up. In addition to losing the opportunity to provide some assistance to these populations, attrition can seriously undermine the integrity of an intervention study and the validity and reliability of its findings. Gaps in basic behavioral and biomedical science. We still lack basic knowledge about many psychological and social processes that contribute to HIV risk and protection. For example, the interactions of sexual behavior, sexuality, and gender identity are not yet well understood, nor is the neuropsychology of drug use and sexual risk. We also lack a full understanding of the biology of HIV transmission and a full complement of appropriate animal models and screening tests for the development of prevention technologies, such as microbicides. Thus, a continued commitment to developing the basic science of HIV prevention is essential. Research translation. It is important that successful and effective HIV prevention interventions be transferred from the domains of scientific research, where they usually are developed, implemented, and evaluated in relatively controlled conditions, to community-based and public health service organizations. It is equally important to integrate July 2000, Vol. 90, No. 7
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community perspectives into the development of HIV prevention research from the beginning, to better ensure the relevance and applicability of interventions. How best to do this translation, transferal, and collaborative research is an underdeveloped scientific question that requires further exploration.
Political and Cultural Challenges HIV/AIDS is an infectious disease whose exponential growth potential has been realized in a global pandemic. It has wiped out nearly whole generations of people in a number of sub-Saharan countries, has produced millions of orphans, and shows no signs of stopping. HIV is transmitted through sex and drug use behaviors that are in many cases illegal or illicit, and the persons who acquire it are often, if not usually, stigmatized and socially marginalized. HIV prevention science does not occur independent of these realities, and it is thus faced with numerous political, cultural, and ethical challenges. There is little support for prevention generally, particularly in American culture. This society is prone to seek medical and technological fixes to problems after they occur, rather than commit to preventing them in the first place. HIV prevention, like prevention efforts in other health areas, is often underfunded and given lower priority than treatment and care in science, practice, and policy circles. Where prevention efforts are supported, it has been difficult to sustain them at the first sign of a therapeutic breakthrough or when budget cuts loom. Mustering empathy and support for prevention activities dedicated to injection drug users, crack smokers, gay men, and commercial sex workers is not easy in America and many other countries where these populations and their behaviors are deemed undesirable, if not outlawed. HIV prevention researchers and practitioners will have to continue to battle prejudice and apathy into the third decade of AIDS, while pursuing their scientific and public health commitments.
Ethical Challenges HIV prevention research must be culturally sensitive and appropriate for the populations in which it is being carried out and to which its findings will be applied. This underscores the need to enhance the participation and the voice of people affected by HIV/AIDS in the determination of research questions and methods to be undertaken in their communities. This has been facilitated through, for example, Community Advisory July 2000, Vol. 90, No. 7
Boards and collaborations between the community and scientists—mechanisms that should be nurtured in the future. Most HIV prevention studies involve either social and behavioral science investigations of sensitive issues, such as sexual activity and drug use, or intervention trials of biomedical technologies that might have unknown physical and psychological outcomes. In all cases, an ethical requirement for the conduct of research is that study participants provide informed consent. But what constitutes “truly” informed consent is a subject of much discussion and disagreement among the scientific community. This issue is particularly exacerbated when study participants have minimal literacy, speak a different language than the research administrators, or have cultural beliefs that do not encourage questioning medical authority. Efforts to improve sensitivity to these factors and to address them in culturally and linguistically appropriate ways are essential to providing truly informed consent in HIV prevention studies. Another related ethical challenge is the determination of appropriate control conditions in randomized trials of prevention interventions. Standards of care change as new developments occur in prevention science. For example, given what is known about the efficacy of consistent and correct condom use for the prevention of HIV and other STDs, researchers have an ethical obligation to provide condom counseling to all participants in prevention trials. They cannot withhold this information. This then makes it difficult, if not impossible, to measure the direct and separate effect of other prevention technologies in a trial, such as with microbicides, since people in the control condition may have prevented disease transmission at rates similar to those in the experimental group (e.g., those given the microbicide) by adopting condom use. A related, but slightly different, ethical issue has been raised in the area of clinical trials for the prevention of perinatal HIV transmission. Once AZT/ZVD administration was proven effective in the “HIVNET 076” trial,26 it became difficult to conduct trials on other therapeutic interventions without providing the “076” regimen as a standard of care to the control group. The dilemma for HIV prevention researchers (as in other health areas) is that the more we learn about effective methods, the harder it will be to test new ones that might be even more effective (including cost-effective). Additional ethical issues that will grow in significance in the next decade of AIDS relate to the involvement of minors in HIV prevention research and investigators’ “duty
to inform.” As HIV incidence increases among adolescents throughout the world, it becomes important to learn more about the risks and resiliencies of minors. But significant legal and ethical rules apply to the involvement of minors in clinical research, including those rules that require the active notification of, or obtaining consent of parents. How to protect the confidentiality and other rights of minors while conducting research that might have important implications for their health and well-being is a challenge that must be addressed. Similarly, when a researcher or clinician discovers that a study participant is the victim (or perpetrator) of abuse or neglect, balancing the requirement to inform public authorities against protecting the confidentiality of the participant is a challenge.
Future Directions in HIV Prevention Research 1. We must continue to develop new methods of prevention, mindful of both their biomedical and behavioral aspects. For example, in the case of microbicides, the biological potential of a compound will mean nothing if it is not used—and used properly—by individuals. Thus, we must develop microbicidal products with a simultaneous view to their physical, behavioral, and social properties. 2. We must focus more attention on HIV prevention among infected individuals. This is increasingly important with developments in HIV/AIDS treatment, as they alter people’s perceptions (if not the realities) of transmissibility. 3. We must develop a “combination” approach to HIV prevention that incorporates a range of biomedical, behavioral, and social interventions that work on all levels of social organization, from individuals to whole societies. In pursuing the “best practices” and “most effective” interventions, we must recognize that these will succeed at the level necessary to eliminate the HIV/AIDS pandemic only if they are applied in combination. Moreover, they will succeed only if they are linked to other efforts to address the macrosocial conditions that contribute to disparate vulnerability to HIV and other infectious diseases and their consequences— that is, efforts to reduce or eliminate inequitable arrangements based on race/ethnicity, sex, sexual identity, and economic class. Thus, HIV prevention science must be better linked with larger social science research agendas that aim to provide better understanding of inequalities and strategies for ameliorating them. Furthermore, it must inAmerican Journal of Public Health
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volve greater partnerships between developed and developing countries, not only in conducting research but also in developing the research capacity of poorer nations and sharing the benefits of research more equitably among rich and poor countries. 4. Future growth in the arsenal of effective HIV prevention strategies requires better public health implementation of proven science-based interventions. This will depend on improved communication between, and relationships among, researchers, public health practitioners, policymakers, and community constituencies, as well as a more developed science of research dissemination. All of us committed to ending the HIV/ AIDS pandemic before we can reflect back on another 20 years must redouble our commitment in all of these areas.
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Contributors The authors conceived, researched, and wrote the commentary together. 11.
Acknowledgment Dr. Coates’s contribution was supported in part by NIMH grant MH42459 (Center for AIDS Prevention Studies).
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