Use of linked clinical and genotypic databases to understand the genetic contributions to clinical outcomes in individuals with HIV

PhD project (3/4 yr research project leading to independent research at the doctorate level)

Professor Jonathan Sterne, Professor Caroline Sabin, Dr Ruth Mitchell


Return to list

Rationale

This project will investigate genetic predictors of response to antiretroviral treatment for HIV infection, based on high density genotyping of 5200 individuals (HIV NIHR BioResource), linked to phenotypic data from the UK Collaborative HIV Cohort Study and UK HIV Drug Resistance Database, two of the world’s most productive HIV cohort studies.
Genome-wide association studies (GWAS) of HIV have mainly addressed correlates of acquisition and disease progression in the absence of treatment: little work has been done in the context of combination antiretroviral therapy (ART). Suppression of viral replication by ART may be insufficient to prevent premature cardiovascular events or hepato-renal pathology, and the risk of non-AIDS cancers may also be raised.

Aims & objectives

This PhD project will focus on identification of genetic predictors of the linked outcomes CD4:CD8 ratio; Dyslipidaemia; Diabetes; and Major cardiovascular events.

Identification of genetic predictors of these outcomes could facilitate early identification of individuals who might benefit from individualised treatments, increased monitoring or intensified prevention measures.

Methods

The HIV NIHR BioResource links with the UK Collaborative HIV Cohort Study (UK CHIC) and the UK HIV Drug Resistance Database (UK HDRD): two of the world’s largest and most productive HIV cohort studies: UK CHIC holds information on >45,000 patients.. These provide historical longitudinal data on CD4 and CD8 counts, HIV RNA values, start/stop dates of ART drugs, and extensive data on key laboratory markers of toxicities or comorbidities. The combined dataset is a unique resource: one of world’s largest genomic-clinical HIV datasets within a predominantly ART-treated population. It will enable investigation of genetic contributions to switches in antiretroviral therapy for toxicity reasons; renal disease progression and cART-associated nephrotoxicity; central nervous system diseases; and cART-associated hepatotoxicity.

References


Created on Oct. 24, 2017, 8:07 a.m.

Edit this page