The status quo
If I approached a vaccine scientist or clinical trialist with a new candidate HIV vaccine for a clinical trial, explaining that I had taken a biology course in college … clearly, we would have a good laugh.
It may come as some surprise, then, the number of times I have heard otherwise levelheaded and well-meaning clinical investigators assert that they had ‘integrated’ a social–behavioral component into their research proclaiming that, after all, they had completed an undergraduate psychology course.
Beyond mere anecdote, the Scientific Strategic Plan of the respected Global HIV Vaccine Enterprise details five working groups Citation[101]; none are dedicated to social science. Although referencing the importance of community engagement in HIV vaccine trials, not one social scientist is listed among the Enterprise’s 111 working group members.
Social science is undoubtedly imperfect. Even our best theory-based and evidence-informed efforts rarely explain even half the variance in human behavior. However, biomedical researchers would not launch a vaccine candidate in a clinical trial without the full weight of existing scientific evidence behind it; even then, the results are often unexpected. In not drawing fully on over 100 years of social science theory and evidence that does exist to address the array of complex social–behavioral challenges in HIV vaccine trials – and future vaccine dissemination – we have strayed from accepted scientific norms Citation[1].
Forward momentum
Recent calls from medical researchers for greater attention to the social challenges of HIV vaccine trials are a positive sign Citation[2,3]. They emerge in the wake of continuing evidence that some of our practices – from community engagement to recruitment, retention and dissemination of results – might be more effectively implemented. Early shutdowns of pre-exposure prophylaxis trials in Cambodia, Cameroon and Nigeria Citation[1,4], and confusion and mistrust among participants Citation[5] and local communities Citation[6] in the wake of termination of the international Step Study HIV vaccine trial due to futility and its unexpected harms Citation[7], invoke the need for greater attention to evidence-informed practices to address social and behavioral challenges of clinical trials.
Acknowledging the problem is a good first step. The US National Institutes of Health and Canadian Institutes of Health Research have taken initiative in sponsoring workshops inclusive of social scientists and clinical researchers to discuss social–behavioral challenges of HIV vaccine trials, and in issuing requests for proposals to this end. Nevertheless, several enduring misconceptions pose obstacles to the meaningful integration of social and biomedical science in HIV vaccine research.
Human behavior does play a substantial role in HIV vaccine research
Beginning from the accurate premise that vaccines are not the same as other HIV prevention technologies, a biomedical approach may treat human behavior as ancillary. An HIV vaccine, it is contended, requires only one or limited doses and its use need not be negotiated in trials or daily life. Alternately, vaginal microbicide research has integrated social science because daily actions by the user impact on both efficacy in trials and real-world effectiveness.
A review of even the limited large-scale HIV vaccine efficacy trials conducted supports a different perspective. The Thai RV144 trial was a monumental undertaking, screening 26,676 volunteers, enrolling 16,402, and resulting in a partially (31%) efficacious vaccine Citation[8]. Yet 2010 of 8197 participants randomized to receive the prime–boost regimen (six doses delivered in four visits) had to be excluded from analysis due to nonadherence. In the landmark AIDSVAX B/B trial, 791 (of 4670) men who have sex with men participants who got tested for HIV outside the study (despite instructions not to), effectively unblinding the trial, evidenced higher odds of unprotected sex and attrition Citation[9].
Thus, in the optimal environment of well-staffed trials with community outreach teams, free product access, financial incentives and prevention counseling, one trial demonstrated 25% nonadherence to the vaccine regimen and the other increased risk behaviors among 17% who tested outside. Not only may these social–behavioral factors compromise efficacy in a trial; they may reduce the effectiveness of vaccines in controlling the global epidemic. The welcome emergence of new partial efficacy HIV prevention options – for example, male circumcision, and oral and topical (i.e., microbicide) pre-exposure prophylaxis – adds further complexity to trial design and implementation; it also further complicates the choices and behaviors of volunteers.
If we build it, will they come?
A related line of reasoning is that we cannot conduct meaningful social–behavioral science until an HIV vaccine is developed. Indeed, assessments of acceptability, uptake and postvaccination risk behaviors may differ in response to actual versus hypothetical products. Nevertheless, the context of 50,000 annual deaths in the USA alone due to diseases preventable by existing vaccines, low hepatitis B vaccine uptake among men who have sex with men and people who inject drugs Citation[10], and ongoing controversy over HPV vaccine roll-out supports the imperative of undertaking social research in advance of a product ready for public licensure. A systematic review (n = 7576) indicates moderate acceptability (65.6 on a 100-point scale) of a high efficacy HIV vaccine and significantly lower (40.4) acceptability in the more likely scenario of a 50% efficacy vaccine Citation[11]. With 2.6 million new infections globally in 2009 Citation[102], a ‘wait-and-see’ approach to addressing the challenges of HIV vaccine dissemination risks millions of new infections that might otherwise have been averted.
Growing recognition of the importance of implementation science – that is, promoting the transfer of scientific findings into routine healthcare policy and practice Citation[12] – supports the wisdom of building social and behavioral research into our trials as well as funding research outside of trials, where the real action takes place: in the community. ‘Translational’ research has thus far focused predominantly on gaps between basic science and development of efficacious products (T1) rather than ubiquitous gaps between clinical trial results and their implementation in real-world settings (T2); in the latter realm, psychology, sociology, anthropology and political science might be more accurately portrayed as the ‘basic’ sciences Citation[12].
Social science is science
The status quo involves reliance largely on biomedical expertise and methods to address the social–behavioral (and biomedical) challenges of HIV vaccine research. Nevertheless, social science is equipped to generate key evidence to guide the conduct of trials. Ethnographic investigations of ‘local vaccination cultures’ Citation[13] and mixed methods research on emic (within culture) understanding of HIV, vaccines Citation[14] and risk behaviors Citation[15], for example, may support evidence-informed community engagement and knowledge dissemination strategies in diverse sociocultural settings. Results from social science investigations designed to guide community preparedness and communication for clinical trials also may provide formative evidence to support the vastly larger (T2) challenges of disseminating future HIV vaccines to millions of people worldwide Citation[16].
Some biomedical researchers wedded to randomized controlled trials as the only progenitor of scientific evidence, however, do not accept the validity of much of social science, particularly qualitative, research. Conversely, adherents of interpretivist or constructivist paradigms may not think it possible to meaningfully research human behavior constrained by a positivist epistemology. A considerable diversity of stances within what are sometimes represented as monolithic and oppositional camps, and productive multidisciplinary collaborations Citation[5,15], suggest ways forward in acknowledging different epistemic positions, identifying shared goals and parameters, and strategizing to effect meaningful collaboration.
Civil society organizations do not substitute for social science expertise
Civil society organizations make vital contributions to planning, monitoring and evaluating biomedical HIV prevention trials often conducted among vulnerable populations. However, they are not a substitute for social science expertise. To presume otherwise places community-based and non-governmental organizations in the regrettable position of representing expertise that they may not possess; it also maintains the gap between social and biomedical science.
What if we don’t like what we find out?
Evidence from social science investigations may support community engagement, risk communication, recruitment, informed consent, retention, risk behavior assessment, prevention counseling and effective dissemination of trial results in diverse sociocultural settings. Ultimately, however, social science is not the handmaiden of biomedical science. Reluctance to engage social scientists in HIV vaccine research may be motivated by concern that some of what we find out might surprise us. Social science investigations, for example, have called into question the veracity of the informed consent process Citation[17] and standardized risk behavior assessments Citation[15]; they have critically examined gaps between willingness to participate and informed decision-making Citation[18] and between the worldviews of community stakeholders and biomedical researchers, which fuel misunderstanding and mistrust Citation[6].
Conclusion
Similar to the biomedical outcomes of clinical trials, sometimes the outcomes of social science investigations may raise as many challenges as solutions. However, the path forward, one shared by social and biomedical science alike, is to build incrementally on evolving evidence. The full benefits of social science can be brought to bear on HIV vaccine research through meaningful inclusion of social science teams in clinical trials (i.e., with openness to revising protocols and commitment to resourcing social–behavioral research) and funding of independent investigations and innovative ideas untethered to the exigencies of particular trials.
Ultimately, the advancement and integration of our best social, clinical and biomedical science will optimize the likelihood of success in our mutual pursuit of the holy grail of AIDS research: a safe and effective HIV vaccine that is widely acceptable and accessible to most-at-risk populations worldwide.
Financial & competing interests disclosure
P Newman’s social–behavioral research on vaccines is funded by grants from the Canadian Institutes of Health Research and the Canada Research Chairs Program. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
References
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Websites
- The 2010 scientific strategic plan of the Global HIV Vaccine Enterprise. www.hivvaccineenterprise.org/sites/default/files/2010%20Scientific%20Strategic%20Plan%20%20WG%20Reports.pdf
- UNAIDS Report on the global AIDS epidemic – 2010. Chapter 2, Epidemic update. www.unaids.org/documents/20101123_GlobalReport_Chap2_em.pdf