The StatinTB proof-of-concept study is exploring whether statins can reduce lung damage and lower the risk of recurrence of TB.

Statin use to boost anti-TB therapies

Mycobacterium tuberculosis (Mtb) causes 1.8 million deaths every year. Treatment is based on use of multiple antibiotics over six months, but disease recurs in 3–5% of patients after they have supposedly been cured. Patients may also continue to experience a deterioration in lung function due to persistent inflammation.

There is growing evidence that statins, drugs widely used to lower cholesterol levels, could be beneficial in treatment of TB. Mtb relies on host cholesterol for survival. As well as lowering cholesterol levels, statins also have anti-inflammatory properties, which may limit the damage caused to the lungs during TB infections. Notably, several studies have found that people who are taking statins have a decreased risk of active TB disease.

The challenge

The StatinTB team is carrying out a rigorous proof-of-concept trial to determine whether use of statins, in addition to antibiotic therapy, reduces the risk of relapse and lessens damage to the lung.

HIV-infected and -uninfected adults will be given a statin, atorvastatin, for 12 weeks at the end of their antibiotic treatment. They will undergo PET/CT (positron emission tomography/computed tomography) scans, which will provide insight into whether active TB disease is still present and the extent of inflammatory damage to the lungs. 

The project

If the StatinTB trial shows that statins have a beneficial impact on lung health as judged by PET/CT measures, it would open the door to large-scale trials to investigate their impact on TB relapse rates and long-term lung function.

Impact


crucial in

widening African

children’s access

to antiretrovirals

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

Mycobacterium tuberculosis (Mtb) causes 1.8 million deaths every year. Treatment is based on use of multiple antibiotics over six months, but disease recurs in 3–5% of patients after they have supposedly been cured. Patients may also continue to experience a deterioration in lung function due to persistent inflammation.

There is growing evidence that statins, drugs widely used to lower cholesterol levels, could be beneficial in treatment of TB. Mtb relies on host cholesterol for survival. As well as lowering cholesterol levels, statins also have anti-inflammatory properties, which may limit the damage caused to the lungs during TB infections. Notably, several studies have found that people who are taking statins have a decreased risk of active TB disease.

The StatinTB team is carrying out a rigorous proof-of-concept trial to determine whether use of statins, in addition to antibiotic therapy, reduces the risk of relapse and lessens damage to the lung.

HIV-infected and -uninfected adults will be given a statin, atorvastatin, for 12 weeks at the end of their antibiotic treatment. They will undergo PET/CT (positron emission tomography/computed tomography) scans, which will provide insight into whether active TB disease is still present and the extent of inflammatory damage to the lungs. 

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.

If the StatinTB trial shows that statins have a beneficial impact on lung health as judged by PET/CT measures, it would open the door to large-scale trials to investigate their impact on TB relapse rates and long-term lung function.

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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