HIV infection is not always protective against superinfection by a second strain, but little data is available on circumstances of superinfection. It is proposed to investigate prevalence, incidence, and virologic, immunologic, clinical and social factors associated with superinfection in a cohort of highly exposed bar workers (600) in rural Tanzania, where three HIV-1 subtypes co-circulate (A, C, D). Once enrolled by voluntary consent, social research on the parameters of a cohort and the community, regular STI treatment and health care, and counselling on HIV prevention will be delivered, and blood and CVL will be collected every three months for three years. The study will help to determine whether superinfection can occur in the face of a fully developed immune response, will define its natural history and virologic outcomes, including the emergence of recombinants, and it will provide a new and innovative approach to define correlates of protective immunity for vaccine development.
The objectives of this project are:
1) to determine the frequency and parameters of superinfection with a second HIV-1 strain in a cohort of bar workers in rural Tanzania who are exposed to HIV-1 subtypes A, C, and D
2) to determine whether superinfection can occur in the face of a fully developed anti-HIV immune response
3) to determine the rate of protection against superinfection; if it is substantial, to determine the protective correlates that can be used for better vaccines
4) to develop a social profile of sex work in the study area and describe the community relationships in order to design more effective interventions, and define parameters important for the future conduct of vaccine trials
5) to provide routine health care and STI treatment among study participants at each of the 12 visits over two and a half years
6) to convey this information to a more effective design of anti-HIV vaccines for the region and an effective development of vaccine trial cohort, and to provide a technical base for the support of vaccine trials.
This project aims to study HIV-superinfections, which may represent the failure of an HIV infection to induce immunity capable of preventing a second HIV infection. Superinfections will be used as a model to investigate correlates of protective immunity. This knowledge may replace the current benchmark – immunity generated by HIV infection – with a more relevant one for improved vaccine design. The project will first establish the frequency of superinfection, then observe whether superinfection occurs in individuals with fully developed anti-HIV immune response, determine the rate of protection against superinfection and, if substantial protraction is verified, determine these correlates for protection. This can contribute to the better design of vaccines. The study design is based on the longitudinal follow-up of a cohort of 600 bar workers in HTAs along the trans-African highway. Enrolment and maintenance of contact will be carried out through an established network of matron/patron. On each visit (every three months for two and a half years), a complete set of specimens (blood and vaginal swab) will be collected, and regular interviews will provide a complete description of the domain of sex work and bar workers in their communities. In-depth interviews will determine the social profile of sex work, risk perception and prevention strategies. Through an information (IEC) campaign, condom use will be promoted along with regular health care and STI treatment, which will be provided as part of the study. Better strategies for HIV/STI prevention will be evaluated and subjects will be evaluated for longitudinal viral load, CD4/CD8 count, STI, HIV infection and superinfection, and other parameters over the two and a half years. The clinical sequel of superinfection and the viral dynamics of the two strains will be investigated in selected individuals. Comparative incidence of infection vs. superinfection will provide the first quantitative measure on how well HIV infection works as a ‘vaccine’ against a second infection and, at the same time, the degree to which this immune response in infection should be sought in the design of HIV vaccines.
1) Determination of the adequacy of the immune response generated by an HIV infection to protect against a second infection.
2) Development of cohorts for future interventions (such as vaccine trials) against HIV and other STIs.
3) Establishment of infrastructure and a technical base for subsequent interventions.
4) Detailed evaluation of the correlates of protective immunity by the comparison of individuals who did and did not become superinfected respectively.
Department of Infectious Diseases and Tropical Medicine
Tel: +49 89 21803830
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