Drs Sipho Mdanda and Sphamandla Ntshangase graduated from UKZN’s Catalysis and Peptide Research Unit (CPRU) with doctoral degrees for their studies investigating anti-retroviral drug’s (ARVs) penetration of the central nervous system (CNS) for the treatment of HIV-associated neurocognitive disorders (HAND).
Currently employed as postdoctoral fellows, the graduates were supervised by leading pharmaceutical chemistry expert, recipient of the National Research Excellence Award for Next Generation Researchers and the current Academic Leader of Research in the School of Health Sciences, Dr Sooraj Baijnath.
Mdanda, who is a postdoctoral fellow at the Wits Advanced Drug Delivery Platform, investigated the ARVs’ plasma and CNS penetration ratio, brain pharmacokinetics and brain spatial bio-distribution patterns of ARVs using advanced mass spectrometry techniques for the treatment of HAND. HAND severely compromises the quality of life of people living with HIV. Late stage AIDS-related illnesses include various neurocognitive disorders, the worst of which is dementia. HAND-related symptoms include short attention span, memory loss, mood disorders, irritability, poor judgment, confusion, and impairment of fine motor skills.
Despite significant advances in the biomedical treatment of HIV-related conditions, the pathogenesis, diagnosis, and treatment of HAND remains poorly understood. According to Mdanda, the main reason for this is that, ‘The central nervous system contributes to the prevalence of HIV as it acts as a compartment in which the virus can replicate independently from ARVs in the system due to blood brain barrier limitations in traversing them into the CNS.’ Mdanda’s findings contribute to better understanding of the range of anti-HIV regimens that highly penetrates CNS and those that halt the neurodevelopmental disorders associated with HIV in patients.
Mdanda was born and raised in Kwa-Maphumulo in Water-Fall Village. He joined UKZN’s Science Foundation programme for learners from disadvantaged schools and went on to obtain a BSc in Applied Chemistry from UKZN followed by a Bachelor of Technology in Analytical Chemistry at Mangosuthu University of Technology before returning to UKZN to complete his Masters and PhD degrees in Pharmaceutical Chemistry. Mdanda said, ‘I come from a family that has challenges like any other humble Black family out there. My parents have no idea of the sacrifices we make because they are not educated, so they cannot lead and guide us. Luckily, I have a brother Nkosi Mdanda who supported every decision that I took. I am also grateful to my supervisors in the Catalysis and Peptides Research Unit (CPRU) who understood my financial challenges and how depressing research can be if things do not go as planned.’ Mdanda loves Afro-house music and believes that music has a way of healing people and restoring one’s energy.
Ntshangase, from the rural village of Jozini, joined UKZN in 2012. He has been awarded a postdoctoral fellowship at the University of Edinburgh, Scotland, and will be joining the Ruth Andrew Research Group. His PHD study evaluated the CNS delivery and localisation of common ARVs to determine their potential efficacy for the treatment of HAND. Ntshangase found that most ARVs localise in the cerebral cortex, corpus callosum, thalamus and hypothalamus and also in the basal forebrain regions of the brain, areas which are known to undergo neurodegeneration during HIV infection.
Working as a team, Ntshangase and Mdanda published six papers in a wide range of international multidisciplinary journals. These papers investigated the distribution of three drugs (efavirenz, tenofovir, and emtricitabine) often used in combination (Atripla) and found that efavirenz localised homogenously across the entire brain, while tenofovir localised in the cortex. Emtricitabine distributed heterogeneously mainly in the thalamus, corpus callosum, and hypothalamus.
They also observed a relatively high abundance of elvitegravir in the thalamus, hypothalamus, and the corpus callosum whereas tenofovir partially localised in the cortex. A high degree of localisation for rilpivirine was fund in the brain regions including the hippocampal formation and the corpus callosum.
According to Baijnath, ‘Using advanced mass spectrometry approaches, the scientists were able to directly detect and visualise clinically important analytes more broadly in biological tissues in order to create an index that better represents drug penetration across the blood brain barrier. This is especially important since many of the current CNS penetration indices are based on cerebrospinal fluid (CSF) drug measurements, which is an incorrect representation of actual brain distribution since the brain has its own independent CSF circulatory pathways. These findings are important for the pharmaceutical effectiveness of ARVs in the treatment of HIV and we hope that they can be used by healthcare professionals to better inform their treatment regimens in combatting HAND. This as neurocognitive disorders continue to be a significant cause of morbidity in people living with HIV.’
Words: MaryAnn Francis