This publication uses cookies

We use functional and analytical cookies to improve our website. In addition, third parties place tracking cookies to display personalised advertisements on social media. By clicking accept you consent to the placement of these cookies.
icon A

EDCTP portfolio: Senior Fellowships

watermark

Dr Christina Thobakgale is studying rare individuals able to keep HIV replication in check, focusing on key cells of the innate immune system.

Innate immunity and control of HIV 

watermark

Despite some progress, HIV/AIDS remains a huge disease burden in sub-Saharan Africa. In South Africa alone, 7.5 million people are living with HIV and 200,000 new infections occur each year.

Intriguingly, a small number of people – known as HIV controllers – seem naturally able to repress HIV replication even without antiretroviral drugs. In so-called ‘elite controllers’, virus replication is undetectable. Less positively, HIV controllers are at increased risk of a range of health complications, particularly inflammatory conditions, as are people on antiretroviral therapy, even if they are controlling HIV replication.

The challenge

watermark

In her Senior Fellowship, Dr Christina Thobakgale is investigating the role of the innate immune response in HIV control and vulnerability to HIV-associated complications. The innate immune response is an early, non-specific defence response, and there is growing interest in its contribution to control of HIV.

Dr Thobakgale will be analysing the properties of different types of innate immune cell from HIV controllers and elite controllers, comparing them to those from people showing more typical responses to HIV infection.

For example, she will be investigating particular types of dendritic cell, which can orchestrate more powerful immune responses to HIV, and natural killer cells, which destroy virus-infected cells. She will also be exploring the properties of monocytes, white blood cells that can also be infected by HIV, which may act as a reservoir of virus and could also contribute to the vulnerability to complications. A particular focus will be on cell metabolism and energy production by mitochondria, which may be altered by HIV infection.

The Senior Fellowship builds on Dr Thobakgale’s past work on the innate immune system and HIV infection, particularly the role of natural killer cells and HIV mutations that enable the virus to evade host responses. In recognition of her promising early research, the South African Ministry of Science and Technology named her runner up in its distinguished young women in science award and she has been nominated to join the Academy of Science of South Africa and the African Academy of Science.

The project

watermark

Dr Thobakgale’s studies are addressing a health problem of particular relevance in South Africa. Her findings will provide insight into the elements of the innate immune response important to HIV control, and those linked to inflammatory complications. The results will have important implications for both the treatment and potential prevention of HIV infections, as well as for minimising the risk of inflammatory complications.

Impact

icon A
icon B


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

watermark

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Despite some progress, HIV/AIDS remains a huge disease burden in sub-Saharan Africa. In South Africa alone, 7.5 million people are living with HIV and 200,000 new infections occur each year.

Intriguingly, a small number of people – known as HIV controllers – seem naturally able to repress HIV replication even without antiretroviral drugs. In so-called ‘elite controllers’, virus replication is undetectable. Less positively, HIV controllers are at increased risk of a range of health complications, particularly inflammatory conditions, as are people on antiretroviral therapy, even if they are controlling HIV replication.

watermark

In her Senior Fellowship, Dr Christina Thobakgale is investigating the role of the innate immune response in HIV control and vulnerability to HIV-associated complications. The innate immune response is an early, non-specific defence response, and there is growing interest in its contribution to control of HIV.

Dr Thobakgale will be analysing the properties of different types of innate immune cell from HIV controllers and elite controllers, comparing them to those from people showing more typical responses to HIV infection.

For example, she will be investigating particular types of dendritic cell, which can orchestrate more powerful immune responses to HIV, and natural killer cells, which destroy virus-infected cells. She will also be exploring the properties of monocytes, white blood cells that can also be infected by HIV, which may act as a reservoir of virus and could also contribute to the vulnerability to complications. A particular focus will be on cell metabolism and energy production by mitochondria, which may be altered by HIV infection.

The Senior Fellowship builds on Dr Thobakgale’s past work on the innate immune system and HIV infection, particularly the role of natural killer cells and HIV mutations that enable the virus to evade host responses. In recognition of her promising early research, the South African Ministry of Science and Technology named her runner up in its distinguished young women in science award and she has been nominated to join the Academy of Science of South Africa and the African Academy of Science.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

Dr Thobakgale’s studies are addressing a health problem of particular relevance in South Africa. Her findings will provide insight into the elements of the innate immune response important to HIV control, and those linked to inflammatory complications. The results will have important implications for both the treatment and potential prevention of HIV infections, as well as for minimising the risk of inflammatory complications.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M