The RZHRG sites in Lusaka, Zambia and Kigali, Rwanda will be participating in Protocols C,D,E, and F, funded by the International AIDS Vaccine Initiative (IAVI). Below please find a summary of all current feasibility studies being conducted by IAVI.

Rationale for Feasibility Studies

Incidence (new infections/year) is a major consideration in the design of efficacy trials and will play a large part in selecting sites for such trials, as well as in calculating the sample size. These feasibility studies will prepare study sites to perform many of the procedures required for a preventive vaccine efficacy trial, including recruitment, retention, counseling, HIV testing, collection of demographic, risk and health data, drawing, processing, storage and shipping of blood samples, cryopreservation and shipping of viable lymphocytes (PBMCs) and recording and analysis of data. Sites will receive the relevant training required to execute a clinical trial according to good clinical and laboratory practices (GCP and GLP respectively).

Protocol A: Prevalence

Enrollment of a total of 6500 subjects in a cross sectional prevalence study to include a detuned assay on the HIV-infected to estimate incidence and pilot field rapid HIV testing using a 2 rapid and ELISA (all specimens for quality control and quality assurance on all specimens and ensure good VCT with high uptake of results. General medical care will be given. HIV-infected individuals will be referred for care and support; HIV-infected pregnant women will be referred for PMTCT. This protocol is nearly complete at four sites: Kenya: Kangemi-KAVI, Kilifi-CGMRC Uganda: Kakira-JCRC, Masaka-MRC

Protocol B: Incidence

Enrollment of a total of 800-1000 volunteers, not infected with HIV, into a follow up protocol with testing every 3 months to estimate incidence, ability to follow subjects, collect information on risk and behavior (to enrich for these in phase II study). This protocol is being developed and once approved, it will be conducted at four sites: Kenya: Kangemi-KAVI, Kilifi-CGMRC Uganda: Kakira-JCRC, Masaka-MRC

Protocol C: Follow up of Incident Cases

A total of 200 incident cases from Protocol B will be followed for viral sequences (also in partners if available), viral load set point and to plot the progression of disease (viral load, CD4, clinical endpoints). Cells will be collected for evaluation of early immunologic control of viral replication. Immunogenetic characterization of the volunteer and partner (if available) will be performed. HIV-infected individuals will be referred for care and support; HIV-infected pregnant women will be referred for PMTCT. This protocol is being finalized and once approved, it will be conducted at six sites: Kenya: Kangemi-KAVI, Kilifi-CGMRC Rwanda: Kigali-PSF Uganda: Kakira-JCRC, Masaka-MRC Zambia: Lusaka-ZEHRP

Protocol D: Safety Laboratory Reference Ranges

A total of 2000 volunteers (50% male, 50% female) who are not infected with HIV and clinically well, will be randomly selected from volunteers in protocol B to have laboratory tests performed that will be used in a clinical trial. The volunteers will be representative of potential participants in an efficacy trial. The mean and standard deviation for each test will be used to select relevant inclusion and exclusion criteria and provide reference ranges in order to interpret adverse events. This protocol is will be conducted at eight sites: Kenya: Kangemi-KAVI, Kilifi-CGMRC, Nairobi-KAVI Rwanda: Kigali-PSF Uganda: Entebbe-UVRI, Kakira-JCRC, Masaka-MRC Zambia: Lusaka-ZEHRP

Protocol E: Cellular Immunology

Standardization of ELISPOT assays in potential participants of future vaccine trials who are at risk for HIV infection to assess the background in potentially exposed but not infected volunteers from protocol B. This protocol is being developed.

Protocol F: Serosurvey

Protocol F is designed to test stored serum samples, collected in previously approved research studies, to assess the background incidence of antibodies against vaccine vectors, such as AAV, Semliki Forest virus, and Adenovirus, that may be used in HIV candidate vaccines in populations likely to participate in future HIV vaccine efficacy trials. The decision regarding which vaccine vector and which vaccine to choose may be dependent upon levels of pre-existing antibody to the vaccine vector in the population of study. Gathering antibody data will guide in the design of potential studies which aim to investigate the effect of antibodies on vaccine immunogenicity. The assays are being validated and the regulatory approval process for the protocol is on going. The assays are expected to be completed early Q2 2005.