Dr George PrayGod

Tanzania

EDCTP portfolio: Senior Fellowships

Dr George PrayGod is investigating whether damage to the gut is linked to the increased risk of diabetes in people living with HIV.

Gut health, HIV and diabetes

People living with HIV are significantly more likely to have type 2 diabetes than those without HIV. In part, this may reflect a higher prevalence of well-established risk factors for non-communicable diseases in people living with HIV. Long-term use of antiretroviral therapy may also increase the risk of diabetes.

One factor that might be mediating this increased risk of diabetes is environmental or HIV-related enteropathy – inflammation of the gut that disrupts gut function and leads to wider systemic inflammation. Gut abnormalities may include reduced release of hormones that promote insulin release, while systemic inflammation may promote insulin resistance, both of which would drive the development of diabetes.

The challenge

Despite its potential importance, enteropathy has been little studied in African populations with HIV. In his EDCTP Senior Fellowship, Dr George PrayGod will take advantage of the ongoing CICADA cohort study, which is examining risk factors for diabetes (but not enteropathy) among people living with HIV in Tanzania.

Complementing the wealth of health, demographic and metabolic data being gathered in the CICADA study, Dr PrayGod will analyse a wide range of biomarkers associated with enteropathy. He will then look for correlations between the levels of these markers and the development of diabetes. His project will also provide capacity-building research opportunities for a PhD and a master’s student.

The project

Dr PrayGod’s Senior Fellowship project will shed light on the possible involvement of enteropathy in the development of diabetes in people in sub-Saharan Africa living with HIV. Encouraging progress is being made in the development of therapies for enteropathy, so evidence of a link would suggest a possible new approach to diabetes prevention among people living with HIV.

Impact


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

Bringing antiretroviral drugs to children

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

People living with HIV are significantly more likely to have type 2 diabetes than those without HIV. In part, this may reflect a higher prevalence of well-established risk factors for non-communicable diseases in people living with HIV. Long-term use of antiretroviral therapy may also increase the risk of diabetes.

One factor that might be mediating this increased risk of diabetes is environmental or HIV-related enteropathy – inflammation of the gut that disrupts gut function and leads to wider systemic inflammation. Gut abnormalities may include reduced release of hormones that promote insulin release, while systemic inflammation may promote insulin resistance, both of which would drive the development of diabetes.

Despite its potential importance, enteropathy has been little studied in African populations with HIV. In his EDCTP Senior Fellowship, Dr George PrayGod will take advantage of the ongoing CICADA cohort study, which is examining risk factors for diabetes (but not enteropathy) among people living with HIV in Tanzania.

Complementing the wealth of health, demographic and metabolic data being gathered in the CICADA study, Dr PrayGod will analyse a wide range of biomarkers associated with enteropathy. He will then look for correlations between the levels of these markers and the development of diabetes. His project will also provide capacity-building research opportunities for a PhD and a master’s student.

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 PrayGod’s Senior Fellowship project will shed light on the possible involvement of enteropathy in the development of diabetes in people in sub-Saharan Africa living with HIV. Encouraging progress is being made in the development of therapies for enteropathy, so evidence of a link would suggest a possible new approach to diabetes prevention among people living with HIV.

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

About us

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 14 European and 16 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases by affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and postregistration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. The second EDCTP programme is implemented by the EDCTP Association supported under Horizon 2020, the European Union’s Framework Programme for Research and Innovation.

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