Ongoing Research

How we do it

Study Population

A retrospective longitudinal study design will be used. Archived samples from a well characterized cohort of patients with AHI (defined as RNA or P24 antigen positive and Antibody negative) from 6 collaborating sites in Africa and Europe will be included, with each patient contributing plasma samples from four time points. In the near future, it is envisaged that a prospective longitudinal cohort of AHI patients will be established at 3 collaborating sites (Durban, Kilifi, and Amsterdam)

Lab Methods

HIV-1 env sequences will be determined by single genome sequencing, with 20 clonal sequences generated from each time point. HLA and KIR profiles will also be determined using sequence based techniques. In addition, profiles from a select panel of innate immune markers will be generated using the Meso Scale Discovery (MSD) electro-chemiluminescence based platform.

Relevance

The proposed project will constitute the largest virus-host dataset of longitudinally collected data of both viral sequences and host innate immune responses to date. Results from the proposed analyses will increase the understanding of HIV-1 pathogenesis and may have implications for therapeutic and prophylactic vaccine design.

Data Analysis

This will be done in a large multi-dimensional Bayesian framework of hierarchical phylogenetic models, allowing for both fixed and random effects prior specifications. This model will test for differences associated within and between patient and group parameters respectively, where all measured virus-host responses will be considered simultaneously.