A complex field of study, Professor Caroline Tiemessen is attempting to understand why some individuals ‘ referred to as elite controllers ‘ are able to be HIV infected, but successfully suppress virus replication to undetectable levels.
This is achieved in the absence of antiretroviral treatment and the immune system response is maintained at an optimal level for many years.
This research will provide insights into how manipulating stem cells or CD4 cells could be used to cure HIV infection, or at very least provide a functional cure (virus suppressed to undetectable levels as in elite controllers).
Tiemessen of the Centre for HIV and STIs (Sexually Transmitted Diseases) at the National Institute for Communicable Diseases, National Health Laboratory Service will at the sixth Wits Faculty of Health Sciences Prestigious Research Lecture on Wednesday present her latest research on a small group of South African individuals referred to as elite controllers and long-term non-progressors.
Long-term non-progressors have detectable viral loads and maintain a good CD4 count (measure of the body’s immunity), often above 500. Most people living with HIV progress to AIDS and CD4 counts below 200 within 3 to 10 years of infection (in the absence of any antiretroviral drug therapy).
‘We are trying to understand the reason why we have people who are less or more susceptible to HIV, how their immune systems see the virus and deal with it and whether they have differences in particular host genes that influence the immune response,’ she explained.
While all will be revealed at Wednesday’s lecture, Tiemessen said this week her research does show differences between the immune responses and genes of those who progress and those who do not. The focus will be on immune responses that recognise small fragments of HIV proteins and on genes that are protective against disease progression that include the HIV co-receptor CCR5 gene.
‘We are trying to learn as much as possible about natural resistance and in a way nature has done the work for us,’ she said. For example it was from early studies of genes of individuals protected from getting HIV infection and those with slow disease progression that CCR5 emerged as a major target for antiviral therapies and now gene therapy strategies. Studying natural resistance will reveal more viral or host targets.
Arbuthnot, Director of the Antiviral Gene Therapy Research Unit at the University of the Witwatersrand’s Faculty of Health Sciences, mainly focuses on finding gene-based cures for Hepatitis B virus infection.
Arbuthnot’s research basically focuses on ways to manipulate genes for therapeutic (treatment) effect. By manipulating and disabling the CCR5 co-receptor gene, cells become resistant to infection with HIV and this may provide a cure. A lack of CCR5 does not have obvious toxic effects.
‘It is essential for the virus to get into the cell to replicate and survive. A useful approach is to disable genes required by the virus to enter target cells and thereby make the cells resistant to HIV,’ explains Arbuthnot.
Using this approach, the HI-Virus could be suppressed and perhaps eradicated.
Explaining how the therapeutic process was likely to unfold if found to have scientific merit a couple of years down the line, Arbuthnot said scientists would remove bone marrow-containing stem cells from a patient or donor. Thereafter the CCR5 genes would be inactivated and the cells would be reinfused into the HIV-infected patient. Proliferation of cells that have the disabled CCR5 cells would result in reconstitution of blood with cells that are resistant to HIV infection.
Arbuthnot agrees that this therapy would be prohibitively expensive within the present set-up and unfeasible in South Africa. However, technology was rapidly becoming more powerful and cheaper.
‘At the moment it is not feasible, but it may well be in future. We can’t simply dismiss it because it won’t work in Africa in its current format,’ he says.
Tiemessen said it was also important for this research to take place in Africa as there was scant information on the local population. Most elite controllers currently being studied are in the West. ‘Our populations are different,’ she said.