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EDCTP portfolio: Career Development Fellowships

Dr Evaezi Okrokoro aims to measure the additional risk of TB infection to HIV health care workers with a view to better training on infection control

TB rates among HIV health care workers

The dual epidemic of HIV and TB has heightened the risk of TB among health care workers especially in sub-Saharan Africa which bears the highest burden of both diseases. Health care workers primarily working in HIV clinics are seemingly at greater risk of Mycobacterium tuberculosis (Mtb) infection as an estimate of 25% of persons living with HIV will have active TB at the initial visit to HIV clinics. The challenge is to measure the additional risk they are exposed to and how they can be protected.

The challenge

Dr Okpokoro aims to measure the additional risk of Mtb infection in health care workers and identify the factors associated with the infection rates among health care workers in HIV care and treatment settings. These findings then should be incorporated in a TB infection control training for health care workers.

He and his team conduct a prospective cohort study that will recruit healthcare workers in hospitals with a high burden of HIV and TB in two states in the Northcentral region of Nigeria. This part of the region has the highest HIV prevalence in the region (i.e. Abuja & Nasarawa). Thirteen hospitals with dedicated PEPFAR-funded HIV care and treatment centres in Abuja and Nasarawa have been selected. A 25% latent TB infection rate among the unexposed group (general health care workers) is assumed and a 35% latent TB infection rate (anecdotal evidence) among the exposed group (health care workers primarily working in the HIV clinics. A minimum of 656 health care workers needs to be recruited. Following informed consent, a TB risk assessment questionnaire is administered and 5ml blood for QFT-Plus and 5ml blood for PBMC is collected from eligible study participants.

The project

Prevalence of Mtb infection among all participants will be calculated as measured by the QFT-Plus. Summaries of Mtb rates will be presented by age, gender, residential district; years of employment at the hospital, etc. Additional analysis will be based on the exploration of immune correlates of protection or risk.

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

The dual epidemic of HIV and TB has heightened the risk of TB among health care workers especially in sub-Saharan Africa which bears the highest burden of both diseases. Health care workers primarily working in HIV clinics are seemingly at greater risk of Mycobacterium tuberculosis (Mtb) infection as an estimate of 25% of persons living with HIV will have active TB at the initial visit to HIV clinics. The challenge is to measure the additional risk they are exposed to and how they can be protected.

Dr Okpokoro aims to measure the additional risk of Mtb infection in health care workers and identify the factors associated with the infection rates among health care workers in HIV care and treatment settings. These findings then should be incorporated in a TB infection control training for health care workers.

He and his team conduct a prospective cohort study that will recruit healthcare workers in hospitals with a high burden of HIV and TB in two states in the Northcentral region of Nigeria. This part of the region has the highest HIV prevalence in the region (i.e. Abuja & Nasarawa). Thirteen hospitals with dedicated PEPFAR-funded HIV care and treatment centres in Abuja and Nasarawa have been selected. A 25% latent TB infection rate among the unexposed group (general health care workers) is assumed and a 35% latent TB infection rate (anecdotal evidence) among the exposed group (health care workers primarily working in the HIV clinics. A minimum of 656 health care workers needs to be recruited. Following informed consent, a TB risk assessment questionnaire is administered and 5ml blood for QFT-Plus and 5ml blood for PBMC is collected from eligible study participants.

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.

Prevalence of Mtb infection among all participants will be calculated as measured by the QFT-Plus. Summaries of Mtb rates will be presented by age, gender, residential district; years of employment at the hospital, etc. Additional analysis will be based on the exploration of immune correlates of protection or risk.

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