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In March 2015 Dr Nightingale completed an MRC Clinical Research Fellowship with a PhD entitled “The role of the central nervous system as a sanctuary site for HIV due to limited penetration of antiretroviral drugs”. He was Principal Investigator of the PARTITION study, a multicentre study collecting CSF from patients with HIV across the UK. Prior to his PhD he completed a Diploma of Tropical Medicine and gained a research fellowship with the Liverpool Brain Infections Group to conduct a randomised trial of IVIG for children with Japanese encephalitis in Nepal. He currently holds a neurology National Training Number at the Royal London Hospital and teaches neurology in Mozambique and Zambia through an educational project he set up with a colleague called NeuroAccess.
Dr Nightingale's PhD work addressed the growing concern that, although modern antiretroviral medications control HIV in the blood, they may not effectively control HIV in the central nervous system where drug levels are much lower. The PARTITION study showed that a proportion of patients with low levels of HIV in blood had higher levels of drug resistant virus in CSF.
Dr Nightingale was subsequently awarded an MRC Young Investigator Award to examine the degree of compartmentalisation of CSF virus through phylogentic analysis. With the support of a further grant from the British HIV Association (BHIVA) he used a cytometric bead array to measure a panel of cytokines and chemokines in CSF showing that compartmentalised virus in CSF, even at very low levels, is associated with potentially damaging neuroinflammation. He collaborated with a Vietnamese group to examine pharmacogenetic and other determinants of efavirenz mediated neurotoxicity in a HIV/tuberculous meningitis coinfected cohort and patients from PARTITION. The neurotoxic 8-hydroxyefavirenz metabolite was found at high levels in CSF which was independent of CYP2B6 genotype but associated with the degree of blood brain barrier breakdown.
In the future he aims to take forward his research on neurological infection and interest in global health by applying for an intermediate fellowship based in sub-Saharan Africa.
Back to: North West England MRC Fellowship Scheme in Clinical Pharmacology and Therapeutics