HIV prevention research has been facing increasing ethical and operational challenges. Factors influencing the design and conduct of HIV prevention trials include a rapidly changing evidence base, simultaneous testing of new biomedical prevention methods and modalities, a large diversity of countries, sites and populations affected by HIV and participating in trials, and challenges of developing and making available products that will be practical and affordable for at-risk populations should success be demonstrated. Clinical researchers and other stakeholders face complex challenges when designing new clinical trials and developing collaborative research plans. To discuss these challenges, a meeting, “Ethical considerations around novel combination prevention modalities in HIV prevention and vaccine trials in resource-limited settings”, was convened by National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIH/NIAID), Division of AIDS on April 22–23, 2013. Meeting participants included clinical researchers, ethicists, research advocates, Institutional Review Board (IRB) chairs, community representatives, research trial participants, and government health officials. Meeting participants came from several sub-Saharan African countries, India, Thailand, Peru, Brazil, and the United States. Key topics addressed were standards of prevention in clinical trials; local health policy challenges; stakeholder engagement; challenges of initiating clinical trials of new biomedical prevention methods such as monoclonal antibodies (mAbs) in resource-limited settings; and selected operational issues including compensation for clinical trial participants, and the need to address vaccine-induced seropositivity/reactivity (VISP/R), in participants in HIV vaccine trials. The goal of the meeting was to identify and discuss ethical challenges in these areas, identify areas of consensus or divergence, and develop recommendations for priority areas to be addressed with subsequent workshops and stakeholder engagement. The meeting consisted of short presentations by experts, case studies, and discussion sessions. Key considerations kept in mind throughout the course of the meeting included effects on the study population, effects on the study design, effects on the study community, health policy considerations, and the opinions and views of important stakeholders.
Here, we offer an overview of the meeting and the key discussion points and recommendations to help guide the design and conduct of future HIV prevention and vaccine research in resource-limited settings. This report is organized in the following sections: (1) study design considerations for efficacy trials of HIV vaccines and other prevention methods; (2) national and local health policy considerations; (3) stakeholder engagement; (4) responsiveness and reasonable availability considerations; and (5) operational issues: compensation and VISP/R.
STUDY DESIGN CONSIDERATIONS FOR EFFICACY TRIALS OF HIV VACCINES AND OTHER PREVENTION METHODS
Given recent positive trial results for pre-exposure prophylaxis (PrEP) for the men who have sex with men (MSM) populations, there are increasing questions about whether or how PrEP should be included in HIV vaccine or prevention trials testing different modalities. For efficacy trials, participants are selected because they are at high risk of HIV infection. Offering prevention modalities in the context of the trial may provide benefits to participants. However, inclusion of additional prevention methods may influence multiple aspects of the trial, such as the risk/benefit assessment for participants, study design considerations, as well as interpretation, generalizability and subsequent translation of trial findings. In the course of this discussion, several considerations were raised.
First, the inclusion of different methods can change the research question being tested in the trial. The inclusion of PrEP may enhance the trial's relevance, if policy makers want to know whether or not a vaccine provides additional protection when given to a group that is already accessing PrEP. However, inclusion of PrEP might decrease relevance of the trial findings if the host countries are unlikely to implement PrEP in the foreseeable future.
Second, during discussion of the uptake of PrEP and its effects on study design, it was recommended that research participants be able to choose whether or not they want to take PrEP; the potential additional protection of the vaccine would be evaluated on top of that. The scientific validity of the trial will not be harmed if different methods are available at different sites, or if some participants have varying levels of adherence to added prevention methods like PrEP, as long as proper randomization of trial arms is conducted. Trials with this design can still be used to assess the effect of an intervention such as a vaccine when participants are randomized to vaccine versus placebo, with PrEP use allowed but not required. However, the combined effects of vaccine plus PrEP cannot be reliably assessed in this scenario, because the PrEP use would not be assigned by randomization.
In addition, if the intervention being tested requires regular adherence, then low adherence will dilute the power of the trial to detect an effect of the intervention; conversely, higher adherence rates preserve the statistical power to make reliable comparisons. If more prevention methods were added and they reduced HIV risk as hoped, three challenges would arise: a larger and more costly trial would be necessary; there would be significantly fewer HIV infection study end points; and there would be greater challenges to defining product-specific contributions to the final study results.
Third, a significant amount of discussion was dedicated to evaluating the utility of factorial designs, in which two interventions are studied in four arms. For example, in a trial combining vaccine with PrEP, the four arms would consist of (1) vaccine plus PrEP, (2) vaccine plus PrEP placebo, (3) placebo vaccine plus PrEP, and (4) placebo vaccine and placebo PrEP. Factorial designs have the advantage of being able to answer two research questions at the same time provided the two interventions do not interfere or interact with each other. Under the assumption of no interactive effects, a factorial design will not increase the sample size of the trial. Lack of interaction seems plausible for PrEP and vaccination as they involve different mechanisms of prevention. Factorial designs, therefore, may be useful for some HIV vaccine and prevention trials.
Fourth, discussions regarding access to PrEP at study sites highlighted an important tension: fairness might dictate a presumption that all sites have equivalent access; however, health policies, including policies regarding PrEP, can vary significantly in different sites and countries. To address this concern, some proposed that a minimum standard ought to be available for all trial sites and then allow for variation across sites given the context and stakeholder views. Fairness within a community (trial participants may have access to more or better methods than others in the community) and post-trial access were also raised as concerns; however, no particular recommendations emerged on how these issues should be handled.
Fifth, there was some discussion regarding to what extent subgroups within a study (eg, MSM, transgender people, women) should receive an intervention, given variable evidence in different populations. Some key questions raised include: (1) Should all subgroups receive the same interventions, although strength of evidence may vary? (2) Should factorial designs be used, with different strategies for subgroups?1 or (3) Should trials be designed with more homogeneous populations? Some meeting participants felt that all subgroups in a trial should be given access, despite conflicting data, unless there is a strong justification for not doing so.
Sixth, meeting participants acknowledged a wide range of mechanisms for accessing new interventions like PrEP. In some cases, research participants might be provided PrEP through a study, or in other scenarios simply referred to other providers. It is also unclear who covers the cost of a background intervention in a trial (eg, sponsors or local health authorities). Importantly, the feasibility of referral to provide new prevention modalities might vary widely depending on local health care policy and infrastructure. The use of demonstration projects for new modalities, for example, PrEP, in the same sites where new efficacy trials are ongoing may be one way to manage these concerns. This allows trial participants to access new methods if they choose, without encumbering the trial, and also allows free choice for those who want the new method but do not want to join the research. Regardless of whether or how PrEP is made available, research participants must always be informed of prevention modalities that are validated in clinical trials as safe and effective.
And finally, meeting participants discussed to what extent additional prevention modalities benefit study participants, noting that there is a need to consider the preferences and needs of communities/study populations, and that the likelihood and degree of benefit needs to be balanced with possible harms from the use of the intervention (eg, the possibility of drug resistance that could arise from incorrect use of PrEP). Benefits might not be limited to HIV prevention interventions and could include other health care services or infrastructure that is used by the community at large. There is no clear guideline or threshold for what level or type of benefits need to be included in clinical trials, thus complicating discussions about standards of prevention and other benefits for trial participants and communities.
NATIONAL AND LOCAL HEALTH POLICY CONSIDERATIONS
Meeting participants emphasized the importance of considering differences in policies in different countries and trial sites. Although current levels of care can vary widely, researchers should consider the future health policy/standard of care landscape and potentially use trials to push for a higher standard of care in a host country. However, current national policies may limit products that can be included in a trial, for example, some drugs may only be used for treatment and not for prevention. According to the Council for International Organizations of Medical Sciences (CIOMS) ethical guidelines, in specific circumstances, there may be a justification for not using the most expensive comparator interventions in a trial testing a more feasible or affordable intervention that is relevant to the health needs of the host country. However, there is no consensus on this point or on how these guidelines should be applied in practice.
As a related concern, there is a need to build better health care infrastructure and research site capacity to enable medically appropriate referrals and to provide for staff training, and scaling up HIV care and prevention in the host countries where research takes place. Although this is not the sole responsibility of researchers, researchers should play a role in working with local organizations and policy makers to plan for the transition to ongoing care after a trial.
Multiple stakeholders need to be engaged early and frequently throughout the clinical trials development and implementation process. Key stakeholders include groups at high risk for HIV acquisition, researchers, sponsors, IRBs, people living with HIV, treatment and prevention program representatives, ministries of health, policy makers, national regulators, religious leaders, community opinion leaders, youth groups, community-based organizations, NGOs, and activists. In particular, researchers should make an effort to collaborate with ministries of health, community members, and other stakeholders throughout the development of a protocol. A commitment to ongoing engagement is valuable for increasing transparency and trust, for avoiding misunderstandings about the intent of the research, for obtaining valuable feedback about the research at early stages when changes can still be made, and for optimizing the conduct of research so that it is appropriate in the local setting. Stakeholders may have valuable guidance about the kinds of products or interventions that will be acceptable to users, or feasible in the local health system. Some stakeholders may be more difficult to engage but nevertheless important for accomplishing the overall goals of research to improve health and health care in the host countries.
Partnering with stakeholders for capacity building in the context of research is also essential. For example, building research literacy for many communities is key to effective advocacy. Community representatives need sufficient knowledge and expertise to advocate for their communities.
RESPONSIVENESS AND REASONABLE AVAILABILITY CONSIDERATIONS
New biomedical technologies for HIV prevention are being explored, among them, the use of mAbs directed at HIV proteins. These antibodies differ from those elicited by vaccines, in that the antibodies are produced in the laboratory, tested for activity against HIV, and then manufactured on a larger scale to be used as injectable products for human use (in contrast, vaccines stimulate the body's own immune system to produce antibodies directed at the appropriate pathogen). mAbs have been used for cancer treatment, autoimmune disease, and respiratory disease treatments but have not yet been used for prevention of HIV. Because production costs for mAbs are high, making their availability to the broader public difficult, there have been concerns expressed that these products may not be feasible or accessible in low-/middle-income countries (LMIC) where the population level burden of HIV is greatest. The discussions surrounding trials of mAbs for HIV prevention raise larger issues about the trajectory of biomedical investigation and the short-term and long-term risks, burdens, and benefits of research.
International ethics guidelines address the concern that research conducted in LMIC that will only benefit patients in wealthier countries may be exploitative, calling for research to be responsive to host country needs and priorities. Although there is no consensus about how this guideline might be interpreted or applied, when considering the question of responsiveness of a trial, several key questions should be asked: (1) Does the research target a priority health need of host communities such as a significant cause of morbidity/mortality? (2) Does the research fill an important gap in scientific/medical knowledge? (3) Is filling the knowledge gap a reasonable means of addressing treatment and/or prevention needs for the host community?
Related to the question of responsiveness to host country priorities is the idea, also expressed in CIOMS guidelines and the Declaration of Helsinki, that interventions proven effective in clinical trials should be made reasonably available to host communities. Unfortunately, predictions about when and how products will be available may not be possible. However, what appears unavailable may eventually become accessible. For example, in the early years of antiretroviral drug development, zidovudine costs nearly $1000 for a 1-month supply, but now triple ARV therapy can cost $25, and many get therapy for free. Therefore, it was recommended that rather than stopping a trial because it does not seem responsive or the product looks unlikely to become available, sponsors should collaborate with various stakeholders (eg, product manufacturers and local health authorities) to ensure availability.
OPERATIONAL ISSUES: COMPENSATION AND VISP/R
Compensation for Study Participation
IRB members and bioethicists sometimes express concern that compensation provided to study participants may constitute an undue inducement to participate in research, which may lead people to disregard research risks they might otherwise find objectionable. To date, there are limited empirical data to confirm or deny worries about inadequate attention to risks. There are unresolved ethical questions about whether it is reasonable, in principle, to pay participants more for riskier studies, or whether compensation should instead strictly cover the time and expenses of participation, such as travel or childcare costs. Although undue inducement is an important consideration, meeting attendees emphasized that a greater focus should be placed on whether or not the trial is ethical to begin with—meaning, for example, risks are minimized and reasonable given the potential benefits. Furthermore, if compensation is reduced too much, study participants might not receive justifiable compensation in light of the time and burden of participation. On a pragmatic level, recruitment to trials can be hampered if there are no incentives or reimbursements to study participants, particularly if invasive procedures are involved.
Several recommendations were made for managing compensation. First, compensation should reflect the local economic context. This, however, may raise concerns about taking advantage of research participants living in a resource-constrained setting. To mitigate these concerns, some have suggested a per site investment that is the same for every site (domestic or international). Individual compensation would be based on local economic context, with the remaining funds going to site enhancements—the goal being to eliminate any motivation to select less costly sites for multisite trials. Second, research participants should be reimbursed for time, parking, and childcare, and there should be prorating per visit so there is no pressure to continue participation. Third, local ethics committees should play an important role in determining fair compensation. Additional questions raised include: (1) Should research participants be reimbursed for travel time? (2) Should there be a difference for phone calls versus in-person visits? and (3) Should compensation be different for urban versus rural research participants?
Throughout the meeting, concerns were raised about research participants' dedication to the research process in light of the fact that many seem to be enrolling in clinical trials to access benefits. This discussion was largely driven by concern regarding the recent results of the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial. Some suggested that participants should not be compensated without being held accountable for adherence during a clinical trial. Others observed that although this is an important discussion, further research is needed and is already ongoing, to fully understand clinical trial participants' motivations and behavior during clinical research studies.
Another critical operational and ethical issue for HIV vaccine clinical trials is VISP/R. Most investigational HIV vaccines induce immune responses that can cause a positive reaction on a standard clinical antibody test for HIV infection. These positive test results can lead to social complications because of the false conclusion made by a caregiver that an individual has acquired HIV infection or a pregnant woman has exposed her fetus to HIV. Accurate determination of HIV status for these individuals requires a more sensitive nucleic acid test, not routinely available, which can distinguish between true infection and VISP/R. Unlike HIV antibody screening tests, nucleic acid tests are not point of care tests, and former vaccine trial participants must be evaluated where their physicians can access nucleic acid tests.
VISP/R persists for participants well beyond the trial and knowledge of the risks of VISP/R play an important role in whether or not participants choose to enroll in trials. Additional concerns may include difficulty with insurance benefits, HIV testing in the military, HIV testing for pregnant women in LMICs who are sometimes tested without consent, stigma and social harm due to perceived positive test results, and concerns regarding privacy and unauthorized disclosure of information. A clinical trial or vaccine may also be blamed for causing HIV infection, because of misunderstandings about the implications of a positive antibody test result.
Given these potential harms or burdens to research participants, several suggestions were made for managing VISP/R. First, VISP/R should be considered in the very early planning stages of a vaccine trial. Second, a VISP/R registry should be created and active measures should be taken to mitigate harms to participants during and after research, including working with the media and stakeholders and education of local health facilities. And finally, considering the privacy concerns, there should be careful maintenance and confidential storage of individual VISP/R records. For further discussion of this issue, it was also noted that The Global HIV Vaccine Enterprise recently had a meeting addressing VISP/R (http://www.vaccineenterprise.org/content/timely-topic-VISP).
This meeting sought to map out some current ethical challenges in HIV vaccine and prevention trials, including the following: standards of prevention in clinical trials; local health policy challenges; stakeholder engagement; challenges of initiating clinical trials of new biomedical prevention methods such as mAbs in resource-limited settings; and selected operational issues including compensation for clinical trial participants, and the need to address VISP/R, in participants in HIV vaccine trials. Meeting participants agreed that there is no single approach for choosing prevention packages and the appropriate study design in combination trials—these issues are complex and will need to be evaluated on case by case basis in different settings. Workshop participants emphasized that early and frequent stakeholder engagement is vital to a fair and transparent process and also to designing ethical and relevant trials. Several important recommendations were also made regarding what stakeholders need to be engaged and when. Often an ethical flash point, concerns about the responsiveness of a trial—and the related concern of reasonable availability—are important but many meeting participants agreed that this should not stop research on new interventions. But rather they recommended that sponsors, drug manufacturers, and stakeholders work together to address barriers to access. The workshop concluded with the recommendation that there be another meeting with a broader range of stakeholders to more substantively address many of the outstanding ethical issues raised by this meeting.
- Because of both trial design and ethical complexities, there is no single approach for choosing prevention packages and for designing combination prevention research trials—these issues are complex and will need to be evaluated on a case by case basis for different clinical trials, countries, and health systems.
- Multilevel stakeholder engagement early on in trial development is vital to a fair and transparent process and also to design ethical and relevant trials. Key stakeholders include groups at high risk for HIV acquisition, researchers, sponsors, IRBs, people living with HIV, treatment and prevention program representatives, ministries of health, policy makers, national regulators, religious leaders, community opinion leaders, youth groups, community-based organizations, NGOs, and activists.
- The responsiveness of a clinical trial to a host community's needs—and the related concern of reasonable availability—were noted as important considerations for clinical research. Although there was consensus that responsiveness to key health needs in the host country, as a general matter, should be required, many meeting participants agreed that it is often impossible to put together plans for delivery and implementation of a new prevention modality, especially during the early stages of research. These concerns should not stop research on promising new HIV prevention interventions. Rather, sponsors and other key stakeholders should work together to address barriers to access as the research agenda progresses.
- Another meeting including a broader range of stakeholders is needed to more substantively address many of the outstanding ethical issues raised by this meeting.
The authors acknowledge Dr. Mary Marovich of the Vaccine Research Program, Division of AIDS, NIH, Ms. Sheryl Zwerski of the Prevention Sciences Program, Division of AIDS, NIH, Dr. Dean Follman of the Biostatistics Research Branch, NIAID, and all the speakers, session chairpersons, and participants at the Ethics Workshop (list of participants given in Appendix 2) for their contribution to the success of the workshop and/or their careful review of this article.
1. Buse JB. Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial: design and methods. Am J Cardiol. 2007;99:S21–S33.
Case Studies Vaccine Case Study
In a multinational vaccine clinical trial, how can the prevention package for participants be structured to take account of differing health system standards, resources, and background conditions?
Researchers funded by NIH are planning a double-blind, placebo-controlled, phase 2b vaccine study. The study is enrolling HIV-negative men and women (age, 18–50 years) including heterosexual persons at high risk for HIV and men who have sex with men (MSM) for a total of 6000 enrollees. Twelve countries will participate, including 10 low-/middle-income countries (LMIC) and 2 high-income countries. All participants will receive prevention packages that include counseling, condoms, STD screening and treatment, and information and referral for male circumcision if interested. Pre-exposure prophylaxis (PrEP) and a rectal microbicide gel have been approved by regulatory authorities and are available in the high-income countries but are not approved or available in the other participating countries. WHO guidelines state that PrEP is indicated for MSM and heterosexual discordant couples; the gel is recommended for MSM.
Vaccine-induced seropositivity/reactivity (VISP/R) is a concern for trial participants at all sites. The clinical trial network will set up VISP/R testing at sites during the study; however, there are concerns about long-term sustainability and accessibility of VISP/R testing, especially in LMIC. Discussions are underway among the network, NIH, and local health authorities about joint responsibility for maintaining VISP/R testing sites but no long-term plan is yet in place.
Some advocates call for PrEP and gel to be offered to all study participants, mentioning concerns about study participants bearing the burden of VISP/R; about fairness across sites in the trial; and that MSM as a disadvantaged and stigmatized group deserve special consideration. Others argue it is premature to offer these products when they are not standard of care; they express concern that the attractiveness of PrEP will cloud participants' decision making regarding study risks. Researchers acknowledge that widespread use of PrEP or gel in the study, if it were to happen, could make it difficult to obtain end points and a much larger study might be needed. The need for VISP/R testing means that continuation of PrEP could be complicated for those who have received active vaccine in the trial.
- Should a uniform approach to provision of PrEP and/or rectal gel be undertaken, across all sites?
- If not, what should be the key criteria, and what stakeholders need to be involved, for determining when/how to include these products?
- Should trial organizers be worried that potential participants will be attracted to the trial to obtain PrEP or gel, and that they will disregard study risks and burdens?
- How should these issues be communicated to trial participants and other key stakeholders, including IRBs/ethics committees? If different IRBs/ethics committees advocate different approaches, how should this be handled?
Monoclonal Antibody Case Study
How should stakeholders evaluate or respond to concerns about feasibility or long-term availability of biomedical products in resource-limited settings, at early, proof-of-concept stages of research?
Monoclonal antibodies (mAbs) have shown some promise in treatment of cancer and other diseases. There are licensed monoclonals for treatment of an infectious disease, respiratory syncytial virus, and for cancer. Work on mAbs for therapeutic or preventive use in HIV is at early stages, consisting of mostly basic discovery and preclinical work; a few early phase human trials have been conducted. There has not been any efficacy study of a monoclonal for prevention or therapeutic intervention in HIV in human volunteers.
NIH is planning to fund a proof-of-concept phase 1/phase 2b clinical study examining the safety, tolerability, dose, pharmacokinetics, and efficacy of a human mAb in resource-limited settings. If the early phase studies go well, additional plans may include testing the efficacy of this product for prevention of sexual transmission of HIV in young adults. The current phase 1 study is enrolling 45 HIV-1–uninfected adults, 18–50 years old. Participants will receive an injection once every 2 weeks for a total of 16 weeks, followed by an additional 16-week follow-up.
- What are the main ethical considerations for doing a proof-of-concept study in a resource-limited setting, when there is an uncertain and lengthy trajectory before any product is likely to be available?
- Is it appropriate to test new prevention modalities in a setting where existing prevention interventions are not yet widely available?
- When considering long-term product development plans, at what stage should feasibility, user acceptability, and availability concerns be discussed, and what stakeholders need to be involved?
- Given worries about future product availability, is lack of industry partnership an ethical concern in an early phase study?
Case Study on New Agents for PrEP
How should new prevention trials including women be designed, in light of the conflicting findings of the 4 large PrEP studies that included women?
A phase 3, placebo-controlled, pre-exposure prophylaxis trial of a long-acting injectable is being proposed in 12 LMIC. The trial plans to include high risk men and women ages 18–50 who are HIV negative. Many, but not all, of the countries have adopted the WHO recommendation of oral PrEP as standard of care for MSM, transgendered women having sex with men, and serodiscordant couples. Some advocates are calling for PrEP to be included in the study for all participants, stating that some women could benefit, and their autonomy in making health care choices should be respected. Critics of this approach state that it is too risky to provide the product to women given conflicting data on effectiveness.
- Should PrEP be provided to women in the trial, given conflicting findings in previous studies? Would it be appropriate to offer women and men different prevention packages in the study, or should both women and men receive the same package?
- Do researchers and sponsors have an obligation to provide specific interventions that are not routinely available in the health care system?
- What stakeholder groups should be involved in discussing and/or deciding what background prevention package should be offered to participants?
- Does the inclusion of women, for whom guidelines are not clear, justify the use of a placebo-controlled trial as opposed to an inferiority or superiority trial? If the trial enrolled only MSM, would a superiority trial be appropriate?
Speakers and Panelists
Elizabeth Adams, Branch Chief, Vaccine Clinical Research Branch, Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, Maryland, USA.
Clement Adebamowo, Associate Professor, Epidemiology and Public Health, Institute of Human Virology, University of Maryland, USA, Chairman, Nigerian National Health Research Ethics Committee.
Chuka Anude, Medical Officer, HJF-DAIDS, Vaccine Research Branch, Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, Maryland, USA.
Nicola Barsdorf, Head, Health Research Ethics, Research Development and Support, Faculty of Medicine, Stellenbosch University, South Africa.
Anant Bhan, Senior Research Consultant, Bioethics and Global Health, ESC Program for Global Health SRC, Pune, India.
Laura Brosch, Director, Office of Research Protections, US Army Medical Research and Material Command Headquarters, Maryland, USA.
Susan Buchbinder, Director, Bridge HIV San Francisco, Department of Public Health, California, USA.
Gina Dallabetta, Senior Program Officer, Global Health Program/HIV Programs, Bill & Melinda Gates Foundation, Washington, USA.
Liza Dawson, Research Ethics Team Leader, Basic Sciences Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, Maryland, USA.
Dean Follmann, Associate Director of Biostatistics, Branch Chief, Department of Intramural Research, National Institute of Allergy and Infectious Diseases, Maryland, USA.
Sam Garner, Bioethicist, HJF-DAIDS, Basic Sciences Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, Maryland, USA.
Sarah Goldkind, Senior Bioethicist, Office of Good Clinical Practice, Office of the Commissioner, Food and Drug Administration, Maryland, USA.
Christine Grady, Branch Chief, Department of Bioethics, Clinical Center, National Institutes of Health, Maryland, USA.
Barney Graham, Branch Chief, Clinical Trials Core Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Maryland, USA.
Scott Hammer, Chief, Division of Infectious Diseases, Columbia University, College of Physicians & Surgeons, New York, USA.
Jessica Handibode, Associate Bioethicist, Basic Sciences Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, Maryland, USA.
Peggy Johnston, Bill & Melinda Gates Foundation, Washington, USA.
Jesse Kagimba, JCRC/IRB Chairman, Research on HIV Vaccines and Drugs, Joint Clinical and Research Foundation, Kampala, Uganda.
James Kublin, Executive Director, HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Washington, USA.
Yvonne Lau, Extramural Research Integrity Officer, Office of the Director, Office of Extramural Research (OER), National Institutes of Health, Maryland, USA.
Dagna Laufer, Senior Director, Medical Affairs, Research and Development, International AIDS Vaccine Initiative, New York, USA.
Udom Likhitwonnawut, Thai NGO Coalition on AIDS, Bangkok, Thailand.
Alex London, Professor and Director, Center for Ethics and Policy, Philosophy, Carnegie Mellon University, Pennsylvania, USA.
Mary Marovich, Program Director, Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, Maryland, USA.
Bonnie Mathieson, Health Science Administrator, Office of AIDS Research, Office of the Director, National Institutes of Health, Maryland, USA.
James Maynard, Associate Director for Communications and Community Engagement, HVTN Core, HIV Vaccine Trials Network, Washington, USA.
Margaret McCluskey, Senior Advisor HIV Vaccines, GH/OHA, USAID, District of Columbia, USA.
Ian McGowan, Professor of Medicine, University of Pittsburgh, School of Medicine, Pennsylvania, USA.
Steve Miralles, Director, Advocacy and Education, Epicentro, Lima, Peru.
Isaac Moseme, Chairman, Community Advisory Group/Board, Aurum Institute, South Africa.
Charles Mwansambo, Secretary for Health, Ministry of Health, Lilongwe, Malawi.
Jim Pickett, Chair, Director of Prevention, Advocacy and Gay Men's Health, International Rectal Microbicide Advocates, AIDS Foundation of Chicago, Illinois, USA.
Punnee Pitisuttithum, Professor, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Luiz Ramires Neto, CORSA—Citizenship, Pride, Respect, Solidarity, and Love (LGBT organization), Sao Paulo, Brazil.
Darpun Sachdev, HIV Vaccine Fellow, San Francisco Department of Health, California, USA.
Jeffrey Safrit, Director of Clinical & Basic Research, Elizabeth Glaser Pediatric AIDS Foundation, District of Columbia, USA.
Fredrick Sawe, Associate Director, International Clinical Research, HIV Military HIV Research Program, Kericho, Kenya.
Seema Shah, Bioethicist, Department of Bioethics, Clinical Center, National Institutes of Health, Maryland, USA.
Jerome Singh, Head, Ethics and Law, CAPRISSA, Nelson Mandela School of Medicine, University of Kwazulu-Natal, Durban, South Africa.
Nirupama Sista, Project Director, Science Facilitation, HIV Prevention Trials Network, FHI 360, Arlington, Virginia, USA.
William Snow, Director, Global HIV Vaccine Enterprise, New York, USA.
Bukelwa Sontshatsha, CAB Member & AVAC, HIV Prevention Advocate, Clinical Trials & Advocacy, Emavundleni Research Center, South Africa.
Jeremy Sugarman, Harvey M. Meyerhoff Professor of Bioethics & Medicine, Berman Institute of Bioethics, Johns Hopkins University, Maryland, USA.
Mitchell Warren, Executive Director, AIDS Vaccine Advocacy Coalition (AVAC), New York, USA.
Sheryl Zwerski, Acting Director, Prevention Sciences Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, Maryland, USA.