Professor Tokameh Mahmoudi, an Associate Professor of Biochemistry at Erasmus MC in Rotterdam in The Netherlands, outlined the findings of some of the latest research being done in the fight against AIDS during a presentation at UKZN hosted by the School of Laboratory Medicine and Medical Sciences.
Mahmoudi is co-founder of the Erasmus MC HIV Eradication Group (EHEG), a multidisciplinary consortium focused on translating basic advances in HIV research into the development of novel therapeutics and testing them. The main research focus is on delineating the molecular events that control HIV transcriptional latency and the HBV-mediated onset of hepatocellular carcinoma (HCC).
She spoke about strategies developed to target the latent reservoir for elimination or inactivation focusing on two different classes of compounds they found which target different steps in the viral gene expression cycle. The preclinical data indicate that these compounds can reverse HIV latency in infected cells.
‘We know a lot about the way the virus hides itself and where in the host genome latent HIV can be found as well as how responsive to the current therapy these latent viruses (hidden in different genomic regions) are,’ said Mahmoudi. ‘These insights have demonstrated that we need to be open to different strategies for HIV Cure, which may require first reversing latency to remove the more easily reactivated latent virus, while at the same time inactivating the remaining virus and harnessing and boosting the immune system to be ready to eliminate any virus that may become reactivated, such that combination antiviral therapy (cART) can be safely discontinued.
Mahmoudi said the challenge now was to come up with a combination therapy targetting distinct steps that regulate HIV gene expression such that the compounds synergise and display a stronger effect more specific for HIV and less toxic for the uninfected cells.
‘Research has already shown that the current cART is very effective in stopping HIV replication, prolonging the life span of infected individuals and reducing transmission. However, cART is not curative due to the establishment of a latent reservoir of cells, which are infected with a replication competent virus that is transcriptionally silent. The silent (or dormant) virus hides in the reservoir and is not expressed in the cells it infects. Therefore a viable cure requires that this latent HIV reservoir is eliminated or permanently contained.’
UKZN lecturer and HIV researcher in the HIV Pathogenesis Programme (HPP) Dr Paradise Madlala, who co-ordinated the seminar, said there was an enormous knowledge gap in HIV pathogenesis and treatment and HIV Cure in non-subtype B infected patients who are by far the majority involved.
Madlala said the tools and technology to close this knowledge gap were there and could be transferred and used to study HIV subtypes predominantly affecting Africa, such as subtype C. Seminars provided opportunities for researchers to participate in collaborative initiatives.
The Erasmus MC has already started a collaboration with UKZN – in which Madlala is the Primary Investigator (PI) – with funding of R3 150 000 being provided by the Medical Research Council over the next three years (2019-2021) to study the sensitivity of HIV-1 subtype C to the different classes of drugs with the goal being to reverse HIV latency.
Words: Lihle Sosibo