RESEARCH ON AIDS IN LATIN AMERICA AND THE CARIBBEAN

ACHR 29/93.10 Original: Spanish RESEARCH ON AIDS IN LATIN AMERICA AND THE CARIBBEAN Division of Communicable Diseases Prevention and Control Program of AIDS and Sexually Transmitted Diseases July 1993.1.. e The issue of this document does not constitute formal publication. It should not be reviewed, abstracted or quoted without the agreement of the Pan American Health Orgonization (PAHO). Authors alone ore responsible for views expressed in signed articles.

~+... TABLE OF CONTENTS I. INTRODUCTION... 1 II. AIDS RESEARCH IN LATIN AMERICA... 2 III. INVENTORY OF AIDS RESEARCH RESOURCES IN LATIN AMERICA AND THE CARIBBEAN, 1983-1991... 3 IV. RESEARCH AREAS AND SUBJECTS... 5 Designs of the studies... 5 Sampling Method... 6 Sample Size... 6 Financial Resources... 6 Scientific Publication of Results... 6 4,

RESEARCH ON AIDS IN LATIN AMERICA AND THE CARIBBEAN I. INTRODUCTION The rapidity of the international response of biomedical and epidemiological research to the AIDS pandemic is unprecedented. In the space of barely 12 years' time between mid-1981 and mid-1993 the clinical syndrome was described for the first time, its causative agent--human immunodeficiency virus--was isolated and characterized, and methodologies for its diagnosis were developed. The means of transmission of HIV was described, in addition to the factors that influence its infectivity and susceptibility to the virus, certain physiopathological aspects of the disease, and the natural history of HIV infection. Opportunistic infections were described, and for some of them, the mechanisms for preventing or curing them. Specific chemotherapeutic agents against HIV were developed, which are currently in use, in addition to various vaccine antigens, presently in the clinical testing phase. Research on social and behavioral considerations identified behavior or risk factors conducive to transmission as well as strategies for its prevention. Despite these advances, the AIDS pandemic continues to spread more rapidly in the developing countries than in the industrialized countries. As of March 1993 the World Health Organization (WHO) had been notified of more than 600,000 cases of AIDS in the world; however, it is estimated that the true figure is some four times higher than the number of cases officially reported. WHO estimates that at the present time, in mid-1993, there are 13 million people infected with HIV throughout the world, and that by the year 2000 at least 40 million people will be infected. The Advisory Committee of the WHO Global Program on AIDS has assigned priority to the following areas of research that the Research Unit of the Global Program on AIDS is promoting in various parts of the world: Development of vaccines (mainly as related to the antigenic variability of HIV and to clinical tests for the study of innocuousness, immunogenicity, and effectiveness of vaccine antigens); Clinical research and development of drugs; Development and evaluation of methodologies for diagnosis of HIV infection; Evaluation of safety measures in blood transfusion; and Epidemiological, social, and behavioral research. 1

The Pan American Health Organization (PAHO) estimates that 2.5 million people in the Americas are infected with HIV. Of this total, 1 million of the infections have occurred in the United States and Canada, and 1.5 million in Latin America and the Caribbean. Although advances in knowledge of the epidemiology of HIV infection in the world have been substantial, research efforts in Latin America and the Caribbean will no doubt help to diminish the spread of infection in the area by providing the specific information needed for evaluating the magnitude of the problem, setting targets for the programs, and improving the efficiency and effectiveness of the interventions undertaken. Current biomedical knowledge, which is generated largely in the most developed countries, is perhaps not always applicable to the Latin American countries by virtue of the social specificity of the behavior associated with the transmission of HIV, the geographical variability of the genetic and antigen structure of HIV strains, and the different regional endemic diseases that may be translated into distinct immune responses and clinical manifestations. Research carried out in Latin America and the Caribbean may shed unique light on the determining factors of HIV infection and the steps that can be taken to prevent it. II. AIDS RESEARCH IN LATIN AMERICA PAHO promotes AIDS research in Latin America mainly through the Research Unit of the AIDS Program and the Program on Health Technology Policies and Development. Since early on in the epidemic the Program on Health Technology Policies and Development has supported research projects on AIDS, and consequently subsidized and contributed to the development of reagents for the diagnosis of HIV Infection in Cuba; the development of sets of reference sera for the evaluation and control of reagents for serological diagnosis of HIV in Argentina; the isolation and characterization of human immunodeficiency virus in Venezuela, Brazil, and Mexico; and a multicenter project for the development of a diagnosis kit for HIV infection in Argentina, Brazil, and Mexico. The Research Unit of the PAHO Program on AIDS is aimed at promoting research on AIDS by national investigators, in accordance with the interests of the countries and with the research priorities of the Global Program on AIDS. Various biomedical and epidemiological research projects were carried out with funding obtained mainly through a contract with the National Institutes of Health in the United States and, on a smaller scale, with funds from PAHO and the Global Program on AIDS. 2

In two research projects carried out in the Dominican Republic and Jamaica the approach was directed toward seroprevalence studies of HIV infection and other retroviruses and their association with risk behavior and sexually transmitted diseases. A research project under way since 1991 in Brazil is aimed at elucidating the risk factors underlying heterosexual transmission of HIV among female partners of infected men. In 1991 a clinical test was carried out in Mexico City to determine the effectiveness of tuberculosis chemoprophylaxis in asymptomatic subjects infected with both M. tuberculosis and human immunodeficiency virus. A multicenter study on the pathology of pediatric AIDS is being carried out in Argentina, Brazil, Mexico, and Uruguay for the purpose of determining the kinds of opportunistic infections prevalent in pediatric AIDS as well as the significance of local endemic diseases as opportunistic infections. In 1993 two research projects will be initiated in Argentina and Mexico to select the best strategies and to determine the effectiveness and reproductibility of simple and economical alternative algorithms for the diagnosis of HIV infection. Two research projects will also be carried out in 1993 to test simple and economical methodologies in the field for counting CD4 lymphocytes as a comparison with the count accepted as standard using flow cytometry. The four projects were subsidized by the Global Program on AIDS and will be carried out with the coordination of the Research Unit of the PAHO Program on AIDS. III. INVENTORY OF AIDS RESEARCH RESOURCES IN LATIN AMERICA AND THE CARIBBEAN, 1983-1991 Between March and September 1991 the Research Unit of the Pan American Health Organization's Program on AIDS, with the support of the WHO Global Program on AIDS, compiled an inventory in order to identify AIDS/HIV-related research projects, either concluded or under way, in Latin America and the Caribbean. The purpose of the inventory was to make a study of AIDS research in the Latin American and Caribbean countries and to place this information at the disposal of the investigators, the agencies that subsidize research on AIDS, and the institutions participating in programs for the prevention and control of AIDS in order to promote collaboration among them and avoid duplication of efforts. 3

In each country the professionals identified as the principal investigators on AIDS were asked to fill out a self-administered questionnaire to provide information on their research projects. The investigators were assisted by national collaborators specifically hired for this purpose. If the principal investigators did not live in the research country, the highest-ranking national investigator in the country completed the questionnaire. e The basic study unit was the research project, defined as the sum total of organized activities carried out by an investigator in an institution to generate scientific knowledge. These activities are normally ordered and systematized in a protocol that specifies, at the very least, the hypotheses, the objectives, the methodology, the work schedule, and the budget allocated for the project. Research was classified into six subject areas: 1) basic sciences; 2) epidemiology, including the natural history of HIV infection; 3) vaccines; 4) diagnosis; 5) clinical studies and procurement of drugs; and 6) social, behavioral, and intervention studies. The research was also classified as descriptive or analytical, according to the purpose of the study, and as longitudinal or cross-sectional, according to whether it had been designed to establish a temporal relationship between the events studied and the study performed. The principal investigators were requested to record the number of scientific publications they had published. They were then asked if the results of the HIV research projects reported had been published and, if so, where. Generally, the results were published as abstracts in the proceedings of scientific meetings, articles in scientific journals in or outside Latin America and the Caribbean, or as books or chapters in books. The inventory identified a total of 652 projects; however, 68 were considered ineligible and another 23 were part of broader research that had already been included in the inventory. Accordingly, the final sample available for the analysis consisted of 561 projects. The first HIV research project in Latin America and the Caribbean listed in the inventory was begun in 1983. Since then, 560 more research projects have been initiated up to the middle of 1991, the limit date of the inventory. Most of these projects (73%) began in 1989 or later, and only approximately one third (35%) had been concluded when the inventory was prepared. Brazil and Mexico, with 143 and 135 research projects respectively, represent half of all the research projects on HIV carried out in Latin American and the 4

Caribbean. Another 20% were carried out in the Caribbean countries, 11% in the Andean subregion, 10% in the Southern Cone, and 9% in Central America. A total of 1,630 investigators participated in these projects, 388 of them as principal investigators of one or more projects. Most of the principal investigators (90%) were natives of the country in which the study was performed. More than one third of the projects (38%) were carried out by investigators from academic institutions; approximately another third (32%) were carried out under the auspices of public health institutions, such as local or national epidemiology services. In addition, 20% of the projects were carried out in clinical establishments without academic affiliation, while the remainder (10%) were the work of nongovernmental organizations. IV. RESEARCH AREAS AND SUBJECTS Of the 561 research projects on HIV, 38% were classified as epidemiological, 30% as social, behavioral or interventions; and 24% as clinical. The topics studied with least frequency were diagnostic procedures (5%) and basic sciences (3%), including studies of the genetic variability of HIV. In the area of epidemiology, topics typically studied were the seroprevalence of HIV and descriptions of the AIDS situation, usually based on epidemiological surveillance sources. Studies of seroprevalence represented 19% of the research projects, which, together with surveys on knowledge, attitudes, and practices (CAP) are the topics frequently studied. Twelve of the seroprevalence surveys were related to a questionnaire on behavior. In the area of social, behavioral, and intervention research, 105 projects (19%) were surveys of CAP as related to HIV. Most of the studies in the clinical and drug area dealt with the frequency of clinical manifestations of HIV infection, classified by apparatus and system or by specific opportunistic infection agent. This topic represented 17% of the 561 projects. The remainder of the studies in this area centered on the effectiveness of antiviral drugs or those employed for treating opportunistic AIDS infections. The designs of the studies varied among the research projects included in the inventory. Nearly 60% were cross-sectional; approximately 19% were longitudinal, including most of the studies on the natural history and the clinical tests; and 4% were of retrospective design. The rest of the studies were reviews of cases, analyses of registries (10%), or laboratory investigations. 5

Sampling Method. Almost half of the studies (49%) were based on convenience samples, and 52% of the cross-sectional studies used such samples. This includes the surveys of seroprevalence and of CAP as well as the descriptive studies of the clinical manifestations of HIV infection classified by apparatus and system or by the specific opportunistic infection agent. Sample Size. Nearly 30% of the studies had samples of fewer than 100 subjects, and another 29%, from 100 to 400. In contrast, 24% had samples of more than 1,000 subjects. The projects using samples of more than 400 were more likely to deal with epidemiological topics. In fact, the unlinked surveys of seroprevalence had large samples because they were usually obtained from detection programs such as blood bank programs. Financial Resources. The 561 projects represent a total expenditure of US$27 million, of which 59% came from international sources. Brazil, Mexico, and the Caribbean represent almost 90% of the funds spent on HIV research. International funds were the sole source of financing of 27% of all the projects. Eight percent received mixed, national, and international financing, 42% were subsidized exclusively by national sources, and 23% did not reveal the source of the financial support provided. Of the projects subsidized with national sources most of the funds came from the state, which in Latin America continues to be the largest source of funding for research. Despite their proliferation, nongovernmental institutions still do not constitute a quantitatively important alternative as a source of financing for AIDS research in Latin America and the Caribbean. Ten percent of the projects with international support employed a professional from outside Latin America as principal investigator. The projects supported with international subsidies have tended to focus on epidemiological and behavior studies, areas that have traditionally been neglected in Latin America. The inventory indicates that AIDS research in Latin America and the Caribbean depends more on international resources than other health areas. In 1986 it was estimated that 18% of the expenditure on health research in developing countries came from external sources. This percentage is 59% in the case of AIDS research in Latin America. Scientific Publication of Results. The results of the projects were revealed in various forms. Nearly one fourth (26%) of the projects disseminated their results mainly through abstracts contained in the proceedings of scientific meetings, 6

approximately 8% published articles in national scientific journals, and 5% in scientific journals outside Latin America and the Caribbean. The remainder (61%) had not published their results, mainly because they had not concluded the project when the inventory data were collected. It was also shown that affiliation with an academic institution increased the likelihood that the results of the study would be published in a scientific journal outside Latin America and the Caribbean. The inventory indicates that 64% of the research projects related to HIV describe the magnitude and characteristics of the problem in each country. This model is common to the areas of epidemiological, clinical, and behavioral research. Epidemiological description of the problem has been provided by seroprevalence and descriptive studies based on surveillance sources, while most of the social and behavioral studies have described the CAP of certain groups or of the general population. Finally, most of the clinical studies have been focused on description of the clinical manifestations associated with HIV. This important research effort, which describes the problem of HIV infection and AIDS in Latin America and the Caribbean, is a response to the need for basic information in order to initiate the planning of control programs in the countries. 9w Such irormation is vital in order to determine the magnitude of the epidemic, obtain reference data to measure the effectiveness of intervention programs, to define certain high-risk behavior for strengthening educational intervention, and to recognize the clinical manifestations associated with the disease caused by HIV. The fact that 73% of the projects began between two and two and a half years before preparation of the inventory, gives credence to the idea that research on HIV in Latin America and the Caribbean is in its initial stages, and accordingly is concerned only with the most pressing needs in planning preventive and health care programs. Nevertheless, important areas remain to be investigated with regard to HIV infection and AIDS in the countries of Latin America and the Caribbean, as, for example, elucidation of the pathogenesis of the virus, the formulation and evaluation of preventive strategies, and the performance of clinical tests of treatments and vaccines. Using broad criteria, 27% of the projects would be classified as research priorities according to the World Health Organization's Global Program on AIDS. In accordance with the pattern observed in other developing countries, very few of the projects in Latin America and the Caribbean deal with priority topics such as the formulation and evaluation of preventive interventions with regard to HIV or the impact of HIV and the care provided to infected people. Areas related to the. ~ diagnosis, prevention, and treatment of HIV infection should also be stressed, since 7

the progress achieved in early diagnosis and clinical treatment in the most developed countries arrives late or remains outside the scope of most of the people who require them in Latin America and the Caribbean. Continuous financing is the key to maintaining research efforts in Latin America and the Caribbean. Total reported expenditures on HIV research in Latin America and the Caribbean amounted to approximately US$27 million during the period 1983-1991. This figure probably underestimates the real expenditure, since many investigators did not include in their budget any expenditures for infrastructure and personnel that were contributed by the country. However, this is a small quantity compared with the expenditures for research on HIV in the most developed countries. For example, Canada, a country with 10 times fewer cumulative reported cases of AIDS than Latin America and the Caribbean, allocated US$30 million for research on HIV between 1988 and 1991. In summary, despite certain limitations in seientific structures, it is necessary to point out the achievements of research on HIV in Latin America and the Caribbean, which have been nourished by a rich tradition in health research. It is also necessary to point out the large problems that remain to be tackled. Questions such as the effectiveness of behavioral and clinical interventions and the natural history of the disease need to be dealt with in greater depth through the use of appropriate methodological designs. Continuous financing is required in order to respond to these needs. Although international financing has already provided support for these efforts, the resources devoted to research in the countries of Latin America and the Caribbean are meager compared with those of the most developed countries. Between 1982 and 1991 US$5,600 million was spent on research on AIDS throughout the world, and consequently the US$27 million invested in Latin America and the Caribbean represents only 0.5% of the total spending on AIDS research in a geographical area that houses nearly 12% of the world's population infected with HIV. The "Inventory of Resources for Research on AIDS in Latin America and the Caribbean, 1983-1991," concluded in April 1992. It was carried out by the Research Unit of PAHO's AIDS Program, coordinated by Dr. M. Weissenbacher, in collaboration with Drs. A. Peruga, P. Cuchí, R. González, and F. Zacarías from the initial stage of collection of the data up through its review and analysis. A total of 1,500 copies were printed and distributed to investigators, universities, health institutions, and institutions that subsidize research on AIDS. 8~

Pe In March 1993 the updating of this Inventory was begun in order to record research projects carried out from 1991 to 1993, in addition to the progress made on the projects described previously. July 1993 will see the conclusion of the phase for the collection of the data, which are being complied by means of a questionnaire prepared on the basis of the previous questionnaire, but modified in accordance with the experience accumulated. The document is being distributed in three languages: Spanish, Portuguese, and English. As of mid-june 350 questionnaires had been received, the majority from Brazil, Mexico, Cuba, and Argentina. 9