For many people in the international HIV/AIDS community, the first thing that would come to mind if asked about the Brazilian national AIDS program§ is “universal free access to antiretroviral drugs.” This would certainly be a good answer, and Brazil takes pride in its groundbreaking role in extending antiretroviral treatment beyond the rich countries of the world. But this is only one aspect of a far more comprehensive effort.
The success of the Brazilian AIDS program can be attributed to many factors and to the cumulative effort of many individuals. Perhaps more than anything else, it is the result of a remarkable consistency since the early days of the epidemic that has extended through many presidents, ministers of health, program directors, and the turnover of countless personnel. This has included a consistent high priority placed on HIV/AIDS, substantial autonomy for AIDS programs, and a relative lack of abrupt changes in structure, policies, and budgets.
The philosophy underlying the program has also been consistent. This includes a respect for human rights and frank communication with the public about issues including sexuality and drug use. It emphasizes broad-based collaboration, including government, nongovernmental organizations, universities, and members of affected populations in the design and implementation of policy. It also includes an assumption that the HIV/AIDS epidemic must be addressed with an evidence-based approach supported by a strong research and development component.
There are 2 sides to being evidence-based. The first is to make policy based on the best use of available knowledge. As a credit to the early leadership of the program, Brazil has strived to do this from the beginning. But there is another side to being evidence-based: generating the knowledge needed to make the right decisions. Brazil has participated in AIDS research all along, but developing a research program specifically directed toward informing programmatic needs has taken time and remains an ongoing challenge. The articles presented in this supplement are some of the fruit of recent efforts in this regard.
The articles speak for themselves. We will not recapitulate their findings or comment on their quality, which is for others to judge. Our intent here is to place them in context and describe the process that led to their creation. We hope this will be useful to those wanting a deeper understanding of AIDS research in Brazil and to colleagues around the world who might want to reproduce some aspects of the Brazilian experience.
After first appearing in the 1980s among men who have sex with men, injecting drug users, and recipients of blood products and growing rapidly initially, the HIV epidemic in Brazil has reached relative stability. In recent years, rates have been similar to those seen in many industrialized countries, with a national HIV seroprevalence in adults of 0.6%1 and 35,000 new AIDS cases each year.2 According to the World Health Organization criteria,1 Brazil continues to have a concentrated epidemic, with the majority of transmission occurring in most-at-risk populations, including men who have sex with men and illicit drug users. HIV prevalence remains <1% among pregnant women, but estimates from the Brazilian Ministry of Health3 based on studies in 10 Brazilian cities in 2008 and 2009 using respondent-driven sampling4-6 indicate that prevalence is much higher in most-at-risk populations such as men who have sex with men (10.5%), illicit drug users (5.9%), and female sex workers (5.1%). Although there has been some increase in heterosexual transmission over the course of the epidemic,2 there is no convincing evidence for the type of self-sustaining heterosexual transmission seen in countries with generalized epidemics.
We will never know the extent to which the current situation is the result of effective prevention efforts or whether the conditions for generalized transmission never existed in Brazil in the first place. But either way, this epidemiological situation has implications for the information needed to guide AIDS programs and the type of research needed to collect this information. In particular, there is a great need for information about at-risk populations that are unlikely to be reached in substantial numbers by standard population-based sampling approaches. Articles in this supplement reporting results from national multicentric studies using respondent-driven sampling represent an effort to reach these most-at-risk populations.
Beyond clear successes in preventing transmission through blood products,1,3,7 and mother-to-child transmission,8 the impact of prevention on the epidemic is hard to measure. But there can be no doubt about the tremendous impact of treatment in Brazil. Studies have documented dramatic improvement in survival among both adults and children.9,10 As people with HIV/AIDS live longer, this success produces new challenges for treatment and research. Aspects related to medication adherence, resistance to antiretroviral drugs, and quality of life come to the forefront for the growing number of Brazilians living with this chronic treatable disease.
Brazil is a country of continental size and vast regional inequalities in social and economic conditions. This presents additional programmatic and research challenges that may be different from those faced by smaller and richer countries. It is not enough to build model programs in centers of excellence. Quality services need to reach the whole country, including the less developed regions that now account for a growing proportion of cases.1 This means that research capacity also needs to be extended beyond the established universities and research institutes in Brazil's more developed south and southeast.
THE NATIONAL AIDS PROGRAM'S ROLE IN RESEARCH
Brazil has been active in AIDS research since the beginning of the epidemic and has probably contributed as much as any other country outside of Europe or North America to the scientific literature about HIV/AIDS. As in most low- and middle-income countries, this research was often funded by international sources and directed by foreign investigators whose interests did not necessarily match programmatic needs in Brazil. The National STD/AIDS program provided training to increase research capacity and funded selected research projects, such as studies on patient survival and the quality of treatment programs.9-11 But there was no integrated plan for developing and funding a research program to meet Brazil's needs.
This changed in 2004 with the establishment of the National AIDS Program's Research and Technological Development Unit. The unit's formation coincided with and was directly related to negotiation of a third round of World Bank funding for the Brazilian AIDS program. Earlier rounds had not included funding for research, and the World Bank was initially reluctant because research is not an activity they normally fund. But this was a priority for Brazil and, to their credit, the World Bank eventually agreed to provide $14.5 million for research over 5 years as 1 of 3 main components of this new round of funding.
One of the first activities of the unit was follow-up on research projects previously funded by the national AIDS program, demanding reports and encouraging the publication of research findings. This included scientific writing workshops and organizing supplemental issues dedicated to AIDS research in Brazil of several peer-reviewed scientific journals including AIDS,12 Revista de Saúde Pública,13 Cadernos de Saúde Pública,14 and Saúde e Sociedade.15
The next step was to develop a transparent merit-based process to fund new research projects in priority areas. Fifteen national and regional calls for proposals were issued over the next 4 years, each with its own specified research topics. Topics were chosen with input from multiple sectors and stakeholders. Funding decisions were made by independent external technical committees based on national and international peer reviews. Overall, 150 research projects were funded out of 524 proposals received.
The process did not end with the issuing of research awards. An intensive ongoing program of monitoring and support from qualified experts provided clear expectations for reporting and publication. Fourteen training workshops were organized on topics including research methods, scientific writing, data base management, and laboratory methods. “Drop out” of projects, a problem in the past, was reduced to almost 0.
Over the 5-year period through 2009, research funding through the national AIDS program accounted for 75% of all sexually transmitted infection/HIV/AIDS research funding in Brazil. In some fields, such as HIV vaccine research, this reached 95%. Products of research during this period included 510 abstracts at scientific conferences, 172 articles in indexed journals, and 163 other publications, representing a substantial improvement in quantity and quality over previous levels.
One aspect requiring special attention was the need to reconcile geographic diversity in research with a merit-based competitive funding process that might have tended to favor the continued concentration of research in traditional centers of excellence. Strategies included targeted research training, incorporating themes of local relevance (such as local endemic diseases) in calls for proposals, and region-specific calls for proposals. Regional calls for proposals for the north, the midwest, the northeast, and the south assured significant research funding in the most deprived areas of the country that have unique epidemiological and social conditions and where funding had previously been so scarce.
Another important strategy was the formation of multisite collaborative networks studying issues such as viral genotypes and most-at-risk populations. These networks include sites that might have had more difficulty fielding such studies on their own, and participation in networks builds capacity and research infrastructure at these sites. Although there is still much more to be done in this regard, we believe that the geographic diversity presented in this supplement demonstrates important progress.
Another important activity of the national AIDS program has been a substantial investment in the establishment of national information systems. These monitor reported cases, antiretroviral drug distribution and resistance, and various indicators of program quality. These databases guide program improvement efforts and can furnish information for research projects.1,16,17
International collaboration also deserves mention. Building a national research portfolio to meet Brazil's needs does not imply opposition to international collaboration. On the contrary, Brazil places no restriction on internationally funded AIDS research that meets technical and ethical standards, and many of the articles in this issue have international coauthors. Furthermore, Brazil continues to be an enthusiastic participant in many bilateral and multinational research collaborations.
This supplement features recent AIDS research in Brazil. Many of the studies presented were funded through the mechanism previously described. Manuscripts considered for inclusion came from 2 sources: invited submissions and manuscripts produced through a training activity in writing for international scientific journals.
For the invited submissions, investigators funded through the national AIDS program were given the opportunity to submit manuscripts by a specified deadline. These were individuals with experience in publishing in international peer-reviewed journals and capable of producing manuscripts suitable for JAIDS without requiring technical assistance. These investigators (often with team members as first author) account for the majority of articles in this supplement.
The second source of manuscripts came from the national AIDS program's continuing efforts to help new individuals and institutions build capacity in all aspects of research, including dissemination. Eighteen promising individuals were selected to participate in a workshop series on writing for international scientific journals. This included didactic presentations and discussions on presenting data, scientific writing, and the publication process. Participants entered with specific research findings of their own or of a mentor that were ready to be disseminated. The heart of the workshop series was for each participant to write a first-authored manuscript suitable for publication. In addition to providing support and protected writing time, activities focused on structured feedback from peers, mentors, and finally from expert invited peer reviewers.
Participants were also provided with assistance in an area that can be a major obstacle for investigators from many countries wishing to publish in top journals: professional translation of their manuscripts into English. All but one of the workshop participants felt more comfortable writing in Portuguese. Of the 16 manuscripts that resulted, 10 met requirements for potential inclusion in JAIDS and were considered for this supplement. It should be noted that the process also included qualitative manuscripts, but these tended not to match the JAIDS structure and length requirements. These manuscripts will be published elsewhere.
A total of 25 manuscripts were submitted to blinded international peer review and subsequent revision, from which the 15 in this supplement were selected. These include 5 resulting from the workshop process. The manuscripts not selected will be submitted to other journals.
The articles in this supplement provide a sample of currently relevant research topics and methods in Brazil. They range from laboratory science to clinical research to behavioral studies of most-at-risk populations. Although the main purpose of these studies was to inform prevention and treatment in Brazil, many of the findings will be of interest elsewhere. The several articles in this supplement about respondent-driven sampling are a good example of this. Brazil did not sponsor these studies because of infatuation with this particular sampling strategy, which certainly has its limitations, but rather to address the practical need to learn more about difficult-to-reach populations. These articles should be of interest not only for their specific findings, which may or may not generalize to similar populations elsewhere, but also because of their methodological contribution, which can be useful anywhere. In building its own AIDS research program, Brazil contributes internationally while helping itself.
The greatest challenge for a developing country like Brazil in building and maintaining an AIDS research program is finding stable funding to support such efforts. The loan agreement between the Brazilian government and the World Bank ratified in 2003 (AIDS III) provided this stability for some years, with a specific component dedicated to science and technology. This produced the excellent results demonstrated by this supplement but ended in 2007, when 33 research projects were funded. Since then, the number of research projects has decreased; for instance, in 2010, the national AIDS program was able to fund only 5 new research studies.
The new loan agreement recently ratified by the Brazilian government and the World Bank (AIDS SUS) focuses on governance, and research is a priority. But this agreement does not include science and technology as a specific component. Therefore, efforts are currently underway to secure new sources of research funding, and some of these are proving successful, including a commitment of approximately $15 million over 4 years from the Brazilian Ministry of Health to support AIDS vaccine research. Other potential sources being pursued include collaboration with existing national and state entities that support research and development. This is likely to be an ongoing struggle.
Aside from funding, the Brazilian national AIDS program will face issues shared by any government seeking to build a research portfolio. These include maintaining a balance between central direction to assure that research meets policy needs while stimulating and rewarding the initiative and creativity of individual investigators and research organizations. Brazil must continue to build a culture of research in nonacademic clinical and prevention services while encouraging researchers to do practical operational research in health care settings and communities. The need to spread AIDS research capacity, both geographically and by types of professionals and organizations involved, will continue to be a priority.
Despite these challenges, we believe that the Brazilian example may be useful for other countries wanting to build and control their own AIDS research capacity. Key aspects of the Brazilian model include recognition of the importance of being evidence-based, a strong central program that sets research priorities with multisectorial input and provides technical support and training, and establishment of a fair, transparent, competitive process for funding research proposals. Building research capacity is a long-term investment that will improve the response to HIV/AIDS in Brazil in many ways. We hope this will allow Brazil to continue as an international leader in the fight against AIDS for many years to come.
The authors are grateful for the support of the National Technical Advisory Committees supporting the Research and Technological Development Unit of the National STD/AIDS and Viral Hepatitis Department represented by Mariza Morgado (Oswaldo Cruz Foundation; president of the Research and Technological Development Committee) and Alberto Duarte (University of São Paulo; president of the HIV Vaccine Committee). They thank the mentors and monitors of the scientific writing capacity building workshop and the international peer reviewers of the manuscripts submitted for this supplement. Finally, they also thank Bruna Fanis, Daniel Deolindo, and Edilson Simplicio for their invaluable support in producing this supplement.
4. Mota RMS, Kerr LRFS, Kendall C, et al. Reliability of self-report of HIV status among men who have sex with men in Brazil. J Acquir Immune Defic Syndr
. 2011;57(suppl 3):S153-S156.
5. Damacena GN, Szwarcwald CL, Souza Junior PRB de, et al. Risk factors associated with prevalence among female sex workers in 10 Brazilian cities. J Acquir Immune Defic Syndr
. 2011;57(suppl 3):S144-S152.
6. Toledo L, Codeço C, Bertoni N, et al. Putting respondent-driven sampling on the map: insights from Rio de Janeiro, Brazil. J Acquir Immune Defic Syndr
. 2011;57(suppl 3):S136-S143.
7. Levi GC, Vitória MA. Fighting against AIDS: the Brazilian experience. AIDS
8. Matida LH, Santos NJS, Ramos AN, et al. Eliminating vertical transmission of HIV in São Paulo, Brazil: progress and challenges. J Acquir Immune Defic Syndr
. 2011;57(suppl 3):S164-S170.
9. Marins JRP, Jamal LF, Chen SY, et al. Dramatic improvement in survival among adult Brazilian AIDS patients. AIDS
10. Matida LH, Ramos AN, Heukelbach J, et al. Continuing improvement in survival for children with AIDS in Brazil. Pediatr Infect Dis J
11. Nemes MIB, Melchior R, Basso CR, et al. The variability and predictors of quality of AIDS care services in Brazil. BMC Health Serv Res
12. Hearst N, Valero J Del A, Bastos FI, Castilho EA, (eds). AIDS research in Brazil. AIDS
. 2005;19(suppl 4):S1-S87.
13. Barata RCB, Latorre MRDO, Aquino EM, Bastos FI, (eds). Sexual behavior and perceptions on HIV/AIDS in Brazil, 1998 and 2005. Rev Saude Publica
. 2008;42(suppl 1):1-137.
14. Caiaffa WT, Bastos FI, (eds). Harm reduction: milestones, dilemmas, prospects, challenges. Cad Saude Publica
15. Saúde e Sociedade. São Paulo: Universidade de São Paulo e Associação Paulista de Saúde Pública. 2010;19(suppl 2):5-133.
16. Inocencio LA, Pereira AA, Sucupira M, et al. Brazilian Network for HIV Drug Resistance Surveillance: a survey of individuals recently diagnosed with HIV. J Int AIDS Soc
17. Matida LH, da Silva MH, Tayra A, et al. Prevention of mother-to-child transmission of HIV in São Paulo State, Brazil: an update. AIDS
. 2005;19(suppl 4):S37-S41.