Title: VIRAL, IMMUNOLOGICAL AND HOST FACTORS ASSOCIATED WITH HIV-1 MULTIPLE INFECTION AND SUPERINFECTION IN A HIGH RISK FISHING COMMUNITY AND A COHORT OF FEMALE SEX WORKERS IN UGANDA
Funder: Medical Research Council

Abstract: A major challenge in the development of an HIV-1 vaccine is the poor understanding of immunological correlates of protection. Natural protective immune responses are being studied by looking at individuals who are highly exposed to HIV-1 but remain uninfected; those who control their viral loads early in infection; and those with different rates of HIV-1 progression. Another approach is to investigate the immune responses among individuals who have already established HIV-1 infection and then subsequently acquire other strains of HIV. This phenomenon, known as superinfection, can involve HIV strains belonging to the same or different clades (intra-clade and inter-clade super-infection, respectively). Lack of superinfection in HIV+ individuals with demonstrable continued exposure might also suggest some existing protective responses. Immunological and virological differences between the superinfected and non-superinfected individuals could help us to better understand protective immune responses and guide rational HIV vaccine design and development. PURPOSE: To characterize the frequency of HIV-1 multiple infections and superinfections as well as the associated viral and host factors that may be relevant for HIV interventions and vaccine formulation. OBJECTIVES:To a) establish the prevalence of multiple infection and the incidence of super-infection. b) To determine the timing of superinfection in relation to primary infection and development of immune responses. c) To compare the viral factors, immune responses, host genetic factors and markers of disease progression in individuals that acquire superinfection compared to those who don’t. DESIGN: This is a prospective cohort study with a nested case-control study to follow up HIV-1 high risk individuals. POPULATION: We will recruit participants from two high-risk populations: 1) the fisher folk cohort and selected landing sites along Lake Victoria in Masaka district 2) Female sex workers from the Good Health for Women Project (GHWP) in Kampala. Two strata will be jointly selected as follows: (a) a “prevalent stratum” of subjects who are HIV+ at baseline (b) an “incident” stratum of subjects HIV negative at baseline who later seroconvert. LABORATORY METHODS: The earliest enrolment sample and that at one and two years will be screened for multiple infection using next generation deep sequencing in the gp41 and p24. In those found with superinfection at year one but absent at enrolment, we will perform a walk backwards analysis of samples to identify the time of superinfection. If no superinfection is identified at year one, the year 2 sample will be analyzed using a walk backwards analysis for detection of superinfection. This will enable the estimation of timing of superinfection. Immunological evaluations will be performed on stored samples taken before and after the time of the superinfection event using flowcytometry and tissue culture neutralization assays. We will also collect data using reproductive health, socio-demographic and risk behaviour questionnaires to assess the risk factors that predispose HIV+ individuals to superinfection.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION