Full Text AI-92-05 PREPARATION FOR AIDS/HIV VACCINE EVALUATIONS NIH GUIDE, Volume 21, Number 8, February 28, 1992 RFA: AI-92-05 P.T. 34 Keywords: AIDS Vaccine Genetics National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: March 30, 1992 Application Receipt Date: May 13, 1992 PURPOSE The purpose of this Request for Applications (RFA) is to support developmental projects designed to establish collaborative studies, involving U.S. and foreign institutions, that (1) develop baseline data for determining the feasibility of conducting AIDS/HIV vaccine trials in international settings and (2) develop capabilities at international sites to conduct HIV vaccine efficacy trials. The NIAID anticipates initiating clinical trials of AIDS/HIV vaccines by December 1993 at domestic sites and shortly thereafter at international locations. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Preparation for AIDS/HIV Vaccine Evaluations, is related to the priority of HIV infections. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001- 0473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal Government. All applicants must demonstrate the existence of a collaborative relationship with a foreign institution and the potential for productivity in the area of epidemiologic research related to HIV/AIDS vaccine testing. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Successful applicants funded under this RFA will be supported through the NIH Exploratory/Developmental Grant (R21) to encourage the development of new research activities. For this RFA, the R21 grant mechanism is used to develop the capability to conduct AIDS/HIV vaccine clinical trials in international settings. The total project period for applications submitted in response to the present RFA may not exceed two years. This RFA is a one-time solicitation. Although there are no current plans to reissue this RFA at any future time, the NIAID may invite competitive renewal applications upon expiration of the initial funding period, contingent on the continued availability of funds for this purpose, adequate progress in research, and the continued need to stimulate research in this area. FUNDS AVAILABLE The NIAID has set aside $3,000,000 for funding the total costs for the initial year of this RFA. The total first-year cost of individual applications, including direct and indirect costs, may not exceed $600,000 per year. It is anticipated that five to six awards shall be made for the first year dependent upon receipt of a sufficient number of applications of high scientific merit. Awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Background on Funding Institutions The Division of AIDS (DAIDS), NIAID, has a primary mission to identify means of preventing, treating, and curing HIV infection and AIDS. The DAIDS has a broad interest in virology, immunology, pathogenesis, epidemiology, diagnosis, and discovery and development of drugs and vaccines for both HIV and opportunistic infections. Within the DAIDS, the Epidemiology Branch and the Vaccine Research and Development Branch will share responsibility for overseeing the development and execution of Preparation for AIDS/HIV Vaccine Evaluations (PAVE) projects. The Epidemiology Branch (EB), within the Clinical Research Program (CRP) of DAIDS, has the responsibility to plan and direct a program of research grants, contracts, and training in support of the identification of risk factors and co-factors for the transmission of HIV, and the study of the natural history of HIV infection, related retroviruses, and associated opportunistic infections. The Vaccine Research and Development Branch, (VRDB) within the Basic Research and Development Program (BRDP) of DAIDS, has primary responsibility to plan and direct a comprehensive program for the discovery and development of vaccines for the prevention of HIV and related retroviral infections. The Branch has undertaken a lead role in organizing scientists into the National Cooperative Vaccine Development Groups (NCVDG-AIDS) for the development of new vaccine candidates and AIDS Vaccine Evaluation Units (AVEU) for phase I and II clinical trials of vaccine candidates. The VRDB and the EB are also implementing plans to prepare for large scale vaccine efficacy trials by identifying suitable study populations and by building appropriate working relationships with national and international agencies, health departments, community-based organizations, and universities. Technical Background The international manifestations of the AIDS pandemic have long provided special challenges as well as unique opportunities for biomedical research. Important differences are found in the natural history of HIV/AIDS in different countries and regions. A number of scientific studies have documented higher rates of heterosexual and perinatal transmission in some developing countries than has been observed in North America and Europe. This transmission may relate, to a limited degree, to socio-cultural and behavioral factors found internationally. In some areas, transmission may be facilitated by the prevalence of cofactors, especially other sexually transmitted diseases (STDs). It is also possible that biological characteristics of the HIV strains or genetic susceptibility of different hosts may correlate with transmissibility. In addition to advances in epidemiologic research, evidence has been accumulating regarding the safety of candidate HIV vaccines in Phase I and II trials. Vaccine protection of non-human primates from HIV or SIV infection has been reported in some studies and led to recognition that there is need for the expeditious development of an infrastructure for vaccine efficacy trials. Vaccine efficacy trials can be most efficiently conducted in cohorts of uninfected volunteers who are likely to continue to experience high rates of HIV transmission despite other preventive interventions. However, before efficacy trials can be appropriately designed, antecedent studies must be conducted to obtain critical epidemiologic and virologic information pertinent to the proposed study community and to gain operational experience in field management techniques. Phase I/II pilot trials, designed to confirm that safety, reactogenicity, and immunogenicity of the HIV candidate vaccine(s) is/are acceptable in specific populations at high risk of transmission also must precede vaccine efficacy trials. While this RFA is not soliciting and will not provide funding for HIV vaccine trials, NIAID intends, through a separate contractual funding mechanism, to support Phase I/II HIV pilot vaccine trials (to determine safety, reactogenicity and immunogenicity in high-risk populations) and Phase III efficacy trials in the future. PAVE projects will be competitive for future funding for vaccine pilot and efficacy trials dependent upon their success in: (1) identifying one or more suitable high-seroincidence cohorts for vaccine testing, including demonstrating capacity for cohort recruitment and retention; (2) documenting HIV seroincidence in a high-risk cohort; (3) demonstrating the ability to collect, store, and ship specimens for assessing HIV seroincidence; and (4) developing and/or strengthening vaccine trial infrastructure at a foreign site including establishment of foreign government and population support of participation in the vaccine trials. An additional criterion for eventual support of HIV vaccine trials at a PAVE site will be the availability of a suitable HIV vaccine candidate. Detailed Research Objectives This RFA seeks to fund developmental projects designed to establish collaborative research studies, involving U.S. and foreign institutions, that (1) provide baseline data for determining the feasibility of conducting AIDS/HIV vaccine trials in international settings and (2) prepare international research sites to conduct HIV vaccine efficacy trials. The specific objectives of this RFA are to: o define the incidence of HIV infection in population groups at high-risk of acquiring HIV infection; o identify selected biological and behavioral co-factors of adult and/or perinatal transmission of HIV; o collaborate in research that studies the distribution of genetic and antigenic variants of HIV in different population groups; and, o strengthen the infrastructure and field management capacity to undertake potential future HIV vaccine efficacy trials. To achieve the objectives of this RFA, all PAVE applicants must provide detailed plans leading to the development of the capability to undertake vaccine trials. Plans should address five components of vaccine site preparedness: o HIV Transmission Research; o Selected Co-Factors of HIV Transmission; o HIV Genetic and Antigenic Variation Determination o Training; and, o Core Services. 1. HIV Transmission Research: All PAVE applications must contain detailed plans to document HIV seroincidence in at least one high-risk cohort. It is anticipated that transmission studies will involve such populations as HIV- discordant couples, male and female commercial sex workers and/or their clients, patients at STD clinics, or other specially identified high-risk persons in clinical or occupational settings. HIV-infected pregnant women and newborns from HIV seropositive mothers may also be recruited for studies of perinatal transmission. It is anticipated that individual PAVE projects will focus their efforts on one or two potentially high-risk cohorts. In some populations, nearly all sexually active young adults may be at high risk for HIV acquisition and therefore a population-based cohort would be suitable. Design of the cohort study should maximize the ability to identify population groups with highest risk for HIV infection. This may be best achieved with innovative techniques of "open cohorts" in which recruited participants with diminishing or lower risk are followed for a finite period and enrollment continues for persons at highest risk. Although the size of cohorts selected for study will depend upon statistical analysis of the anticipated levels of transmission with a reasonable degree of confidence in the seroincidence estimates, most applications should plan and budget for a cohort size of about 2,000 persons because that will best simulate the field management challenges in possible future efficacy trials. Applications should include a discussion of the feasibility of organizing high risk cohorts within a geographic area based upon antecedent information about the existence and accessibility of such populations (e.g., clinic records, seroprevalence studies). Study designs must include convincing discussion of field study techniques that are successful in maintaining long-term contact with high-risk cohorts and that have in place appropriate surveillance systems to diagnose and document newly-acquired HIV infections. 2. Selected Co-Factors of HIV Transmission: Each PAVE application must include plans for research that will document and quantify the influence of potentially important biological and behavioral transmission cofactors. In view of the recognized importance of other STDs in HIV transmission, PAVE applicants should consider inclusion of protocols that document the prevalence and potential role of such cofactors in the study population, including syndromes and populations which, to date, have received inadequate attention. Other possible co-factors of HIV transmission that should be considered in the research design, depending upon the types of high risk cohorts under study, could include: (a) the presence or absence of concurrent infections, (b) stage or severity of disease in the infected individual who may be the source of new infection, (c) age, (d) parity, (e) race/ethnicity, (f) circumcision status in men, (g) cervical ectopy status in women, (h) condom and/or contraceptive use, and other relevant factors. Possible behavioral co-factors of transmission (e.g., type of sexual practices, number of sexual partners, nature of sexual networks, menstrual and/or non-menstrual coital bleeding, douches, vaginal suppositories or other agents, drug use,) should also be considered, whenever appropriate, in research design. Research relating to co-factors of HIV transmission will be especially critical in countries or areas where other public health intervention efforts are underway to diminish transmission (e.g., promotion of condom use; active STD surveillance, diagnosis and treatment; and targeted programs for sex workers and their clients). 3. HIV Genetic and Antigenic Variation Determination: Each PAVE application must include a sampling strategy for obtaining 50 virus isolates (e.g, viably preserved cells or fresh heparinized whole blood) from HIV-infected individuals who are representative of the population that would be suitable for enrollment in potential future vaccine pilot and efficacy trials. Serum should also be collected from these same individuals. Plans should include provision for shipment of isolates and serum to Rockville, Maryland, where the NIAID will provide PAVE awardees with access to laboratories for genetic sequencing and immunological variation analysis at no cost to the PAVE project. These services will support the PAVE awardee in the optimal evaluation of endemic HIV variants of relevance to vaccine design and testing. 4. Training: All PAVE applicants must include plans for training foreign nationals in research technologies related to the preparation and conduct of a HIV vaccine clinical trial. Training should result in the transfer of appropriate technology and assist in developing self-direction and self-sufficiency in research in the foreign country. The areas of training may include, but are not limited to: HIV epidemiology, laboratory techniques for HIV detection, laboratory assessment of vaccine immunogenicity, and clinical trials statistical methods. Although funding for this training can be supported within PAVE projects, proposals will be judged to be most competitive and cost-efficient if they are able to coordinate and secure financing for training plans from other sources such as the NIH Fogarty International Center, PAHO/WHO, the NIAID AIDS Vaccine Evaluation Units (AVEU), the "International Course in Surveillance and Applied Epidemiology for HIV and AIDS" of the CDC, private foundations, or other appropriate funding organizations. To the extent possible, NIAID staff may assist in facilitating the identification of such funding sources. 5. Core Services: To provide for common administrative and technical support of the scientific components of the PAVE, applications must include a description and budget for a core services component. This component could cover three types of service units: Administration, Laboratory Services, and Data Management. A. Administration: PAVE applicants must present an organizational structure and plan for the effective management of the developmental research including the identification of senior U.S. and foreign scientist staff, "on-site manager(s)" and other key staff. Plans must also be made for the U.S. Principal Investigator and a key principal foreign project manager to participate in a single two-day "Progress Review Meeting" in Washington DC after nine months of activities. In addition, the U.S. Principal Investigator must plan on a one-day meeting with NIAID staff for a review of initial plans within 60 days of award of grant and again for progress reviews after six months, 15 months, 18 months and 21 months from the date of award. B. Laboratory Services: Applicants must present clear plans to establish and maintain a high quality HIV diagnostic laboratory facility at the foreign site, including adequate procedures for specimen collection, storage, shipment, and quality control. It is recommended that PAVE projects develop or utilize a central laboratory service for project needs although, in selected circumstances, the use of several laboratory sites for different types of analyses may be more advantageous and is acceptable if coordination can be assured. Essential local laboratory capability for the PAVE should include HIV ELISA and Western Blot, relevant methods for diagnosis of STDs, and basic hematologic and clinical chemistry testing. Projects will also be expected to retain serum samples at -70 C conditions in a repository maintained in the foreign site for the duration of the project. Other U.S. or foreign-based laboratory studies that are essential to the specific proposed research activities should be carefully justified. C. Data Management: Applicants must assure that plans and staffing are adequate to ensure appropriate management of research data, including: development of forms, data input, processing, and timely analysis. It is recommended that data management services be centralized in each PAVE project. SPECIAL REQUIREMENTS All applicants for a PAVE grant MUST satisfactorily address the following items: l. Applicants must develop and submit milestones/timeliness for each of the five research components (see preceding section) that identify major steps and anticipated accomplishments. Milestones could include such events as: (1) initiation and completion of recruitment of a high-risk cohort, (2) follow-up visits for cohort members, (3) initial analysis of seroincidence in the cohort, (4) acquisition and shipment of specimens for genetic and antigenic variation determination, and (5) training of foreign staff. 2. Applicants must document that a potentially productive institutional relationship has been established between the U.S. and foreign institution(s) collaborating in the PAVE project. If the PAVE project builds upon an existing international collaborative research relationship, applicants must cite scientific publications and presentations at international scientific conferences that have resulted from such collaboration. The application must include one or several letters of agreement from representatives of the relevant foreign institution(s) AND from the appropriate institution of the foreign government in which foreign components of the research will be conducted (e.g., Ministry of Health, National AIDS Commission, National AIDS Control Program). Applicants are reminded that NIH regulations do not permit grant funds to be expended on customs payments to foreign governments. It will be desirable for the foreign government to provide a letter agreeing to permit duty-free importation of equipment and supplies necessary for the PAVE project and to facilitate the transfer of laboratory specimens and samples from the foreign site for analysis in U.S. laboratories. 3. Applicants must describe, to the extent known, other vaccine preparation efforts in the foreign site, including those that may be sponsored by a foreign or an international organization; and, whenever applicable, describe the relationship between these efforts and the PAVE. 4. If any protocol or component includes the use of clinical facilities, applicants must provide specific information pertaining to present patient load and projections for patient enrollment and follow-up in clinical investigations. In addition, a detailed description of the facilities must be provided and must include availability of equipment, reliability of supply systems and electrical power, training of personnel, and maintenance of quality control procedures. 5. Since most of the research will be conducted in a foreign country, funds must be allocated accordingly. The NIAID has determined that at least 70 percent of all direct costs should be spent in the foreign country. If the budget request shows the foreign component to be less than 50 percent, the application will be returned to the applicant without further review. If the budget request shows a foreign component of between 50 to 69 percent, a strong justification must be provided for the reduced foreign component. These justifications will be considered on a case-by-case basis. 6. Applications must assure that research participants will be provided treatment consistent with the standards of care for the country in which the PAVE is located, for any STD diagnosed in any component of the PAVE. 7. The NIAID assures that all specimens and viral isolates sent to the NIAID for genetic and antigenic variation analysis (See Detailed Research Objectives, Paragraph 3., HIV Genetic and Antigenic Variation Determination) will be used exclusively for this purpose. No other uses will be made of these materials without express written agreement between the U.S. and foreign authorities responsible for the PAVE project. 8. Each of the five components of the research plan (see previous section on Detailed Research Objectives) must have a separate budget and each must include justifications for all requested costs. The milestone chart must be used to determine timing of budget requests. The budget must include requests for the Principal Investigator to travel to Washington three times a year, and for one key personnel at the foreign site to travel to Washington once in the first year. Because the intent is that 70 percent of all directs costs be spent in the foreign country, applicants must identify in the budget, costs that are considered foreign and those that are considered domestic. The listing below provides some guidance for identifying foreign and domestic costs: o All costs for foreign personnel and all equipment and supplies used at the foreign site must be identified as foreign. o Travel for staff from the foreign site to the U.S. will be considered a foreign cost. Travel of U.S. staff to the foreign site will be considered a domestic cost. o Equipment and supplies purchased in the U.S. but shipped and used at the foreign site will be considered foreign. o Salary for personnel, employed by the U.S. applicant but spending 80 percent or more of their committed time at the foreign site, will be considered foreign. o Travel and supplies for the training of foreign personnel will be considered foreign. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 in Section 2, A-D of the Research Plan AND summarized in Section 2, E. Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. Protection of Human Subjects Applicant institutions are reminded that adequate protection for human subjects in international collaborative research is an essential requirement for the NIH. Awardee institutions, each subordinate entity to the Awardee and each performance site, whether institutions or independent investigators, must agree that the rights and welfare of human subjects involved in research under this cooperative agreement shall be protected in accordance with 45 CFR 46. As a condition of award, not as a condition of application, applicants and affiliated performance sites are required to designate an IRB and possess an applicable assurance of compliance which has been approved by the Office for Protection from Research Risks (OPRR) of the NIH. Applicants will be notified if additional information is required on this matter. LETTER OF INTENT Prospective applicants are encouraged to submit a letter of intent, by March 30, 1992, that includes a brief description of the study population and the thrust of research activities; the names of the principal and other key investigators, if known; the identity of the U.S. and foreign institutions involved in the collaboration; and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NIAID staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to: Robert D. Fischer, M.D., M.P.H Epidemiology Branch, DAIDS National Institute of Allergy and Infectious Diseases Solar Building 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-6177 FAX: (301) 402-1506 For overnight or courier service, letters are to be sent to the same address BUT USE "Rockville, MD 20852" in place of "Bethesda, MD 20892," APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for this grant. These forms are available at most U.S. institutional business offices and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda MD 20892, telephone 301/496-7441. The RFA label available in the form PHS 398 must be affixed at the bottom of the face page of the original signed application. Failure to use this label could result in delayed processing of the application such that it may not reach the received committee in time for review. To assure the identification of the application with this RFA, mark "Yes" in item 2 of the face page of the application and type "Preparation for AIDS/HIV Vaccine Evaluation, RFA AI-92-05". Submit a signed, typewritten original application, including the Checklist, and three signed, exact, single-sided photocopies, in one single package to: APPLICATION RECEIPT OFFICE Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the same time, two exact copies of the application must be sent directly to: Dianne E Tingley, Ph.D. Scientific Review Administrator AIDS Review Section, DEA National Institute of Allergy and Infectious Diseases Solar Building, Room 4C34 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-0818 If sending the application by overnight mail or courier service to Dr. Tingley, send the application to the above address BUT USE "Rockville MD 20852" in place of "Bethesda, MD 20892." Applications must be received by May 13, 1992. If an application is received after that date, it will be returned to the applicant. The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG also will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. Applications will be reviewed by NIAID staff to determine completeness and responsiveness. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, it will be returned to the applicant. Those applications that are complete and responsive may be subjected to triage by an NIAID peer review group to determine scientific merit relative to the other applications received in response to this RFA. The NIH reserves the right to withdraw from competition those applications judged as non-competitive and will so notify the applicants. Those applications judged to be competitive for award will be further reviewed for scientific and technical merit by the AIDS Research Review Committee convened by the Division of Extramural Activities, NIAID, during July 1992. The final level of review will be provided by the National Advisory Allergy and Infectious Diseases Council in September 1992. REVIEW CONSIDERATIONS The application must be directed to the objectives specifically identified in this RFA. Additional factors that will be considered in the scientific and technical review of the application will include: o completeness and feasibility of the plans (including proposed milestones and timetables) for meeting the objectives of this RFA; o documented evidence of commitment of the foreign institution and the foreign government to the research collaboration; o administrative experience and competence of the Principal Investigator and key staff in the development, implementation, and management of international research and training programs including seroincidence and vaccine studies; o adequacy of the existing physical facilities and resources of the collaborating domestic and foreign institutions; o applicant's accommodation to the NIH policy for including women and minorities in study populations and sensitivity to the foreign country's culture; o evidence within the research design of the promotion of technology transfer and the development of self-direction and self-sufficiency in the foreign country research team; o evidence that human subjects are adequately protected, and that clinical data and biohazard safety monitoring are accorded a high priority. Applicant institutions are encouraged to discuss their research plans with the in-country missions of the U.S. Agency for International Development and the local offices of the World Health Organization or Pan American Health Organization in the countries in which the PAVE will be situated. Letters of support for the project from these in-country missions of the above identified agencies are desirable but not required prior to grant submission. AWARD CRITERIA The anticipated date of award is September 30, 1992. The following will be considered in making funding decisions: o quality of the proposed project as determined by peer review o availability of funds o program balance among research areas of the announcement o geographic distribution among applications under consideration The training component of applications will be judged on cost efficiency and adequacy of coordinating and securing financing from other sources. Approved grants will be funded for up to two years. Continued support for PAVE projects beyond the first year will be based on the satisfactory performance and demonstrated ability of the grantee to assemble and retain cohorts that may be of importance in future HIV vaccine trials. The NIAID will make the judgment on funding the second year of the developmental project based on the annual report and information gained from interim program review meetings. Criteria used to evaluate the progress of PAVE projects will include: o success in recruitment and retention of a high-risk seronegative cohort; o adequate precision in the measurement of seroincidence rates; o adequate field management, laboratory, trained staff, and patient and specimen transportation infrastructure; o continuing foreign country support for the project; o foreign and U.S.-based ethics review groups capable of judging a vaccine research plan; o adequate capacity to collect and ship blood specimens for required laboratory studies including the maintenance of a local repository of serum samples from the cohort; o sociopolitical environment conducive to completion of an HIV vaccine pilot study; o likelihood that a site could eventually do a full-scale HIV vaccine efficacy study; o cost-efficiency of site research capacity; and o appropriate geographic distribution of awards. INQUIRIES Questions regarding programmatic aspects of and responsiveness to this RFA may be directed to: Robert D. Fischer, M.D., M.P.H. Epidemiology Branch, DAIDS National Institute of Allergy and Infectious Diseases Solar Building 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-6177 FAX: (301) 402-1506 Inquiries regarding matters pertaining to the review of this application may be directed to: Dianne E Tingley, Ph.D. Scientific Review Administrator AIDS Review Section, DEA National Institute of Allergy and Infectious Diseases Solar Building, Room 4C34 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-0818 Inquiries regarding fiscal matters may be addressed to: Jane Unsworth Chief, DAIDS Section Grants Management Branch National Institute of Allergy and Infectious Diseases Solar Building 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 For overnight and courier service, correspondence to the above persons may be sent to the same address BUT USE "Rockville, MD 20852" in place of "Bethesda, MD 20892" AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856, Microbiology and Infectious Disease Research and No. 93.855 Immunology, Allergic and Immunologic Diseases Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulation 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Authority for the international aspects of this program are provided by Public Law 86-610, the "International Health Research Act of 1960" and Public Law 100-607, the "Health Omnibus Program Extension Act of 1988." SELECTED REFERENCES INTERNATIONAL HIV TRANSMISSION EPIDEMIOLOGY Bartholomew C, Cleghorn F. Retroviruses in Caribbean. Bull Pan Am Health Organ 1989; 23-76-80. Berkley SF, Widy-Wirski R, Okware SI, Downing R, Linnan MJ, White KE, Sempala S. Risk factors associated with HIV infection in Uganda. J Infect Dis 1989; 160:22-30. 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