Dr Joseph Fokam
Cameroon
EDCTP portfolio: Career Development Fellowships
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Dr Joseph Fokam will monitor adolescents living with HIV for a year as they go through treatment transitions to ascertain how they respond.
Drug resistance and HIV-1 variability in adolescents
Nine out of every ten children living with HIV globally are in sub-Saharan Africa. Monitoring remains suboptimal even as these children grow older. Over 2.1 million HIV-infected children are growing towards adolescence with the potential to reach adulthood. However, despite HIV-related mortality decreases overall, it is increasing among adolescents living with HIV (ALHIV). The challenge is to develop strategies for the transition of adolescents from paediatrics to adult-healthcare. This is critical to ensure successful treatment response, longer life expectancy and their future contribution to their society.
The challenge
The study is an observational, prospective and open cohort-study conducted among 250 ALHIV (10-19 years old) receiving ART, in the central region of Cameroon. Dr Fokam monitors the response to first- and second-line regimens and profiles drug resistance and HIV-1 variability during a 12 months follow-up. Specifically, the study evaluates the rate of immune-virologic failure at enrolment, month 6 and month 12; acquired mutations associated with drug resistance; HIV-1 subtype distribution; genetic variability in circulating (plasma) versus archived (cellular) viral strains; and early warning indicators of HIV drug resistance. Survival analysis will be performed during the 12 months follow-up. Primary outcomes are rates of virological failure, acquired HIVDR, and mortality.
The project
Dr Fokam expects that the findings will provide evidence-based recommendations to ensure a successful transition from paediatrics to adult ART regimens. Secondly, the results will highlight further needs of active ART combinations to achieve reduced morbidity and mortality in populations of adolescents living with HIV in sub-Saharan Africa. Without a successful transition of adolescents, the success rate of paediatric ART might be quickly jeopardised, with possible HIV-1 drug-resistance emergence, especially after years of paediatric ART exposure.
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
Nine out of every ten children living with HIV globally are in sub-Saharan Africa. Monitoring remains suboptimal even as these children grow older. Over 2.1 million HIV-infected children are growing towards adolescence with the potential to reach adulthood. However, despite HIV-related mortality decreases overall, it is increasing among adolescents living with HIV (ALHIV). The challenge is to develop strategies for the transition of adolescents from paediatrics to adult-healthcare. This is critical to ensure successful treatment response, longer life expectancy and their future contribution to their society.
The study is an observational, prospective and open cohort-study conducted among 250 ALHIV (10-19 years old) receiving ART, in the central region of Cameroon. Dr Fokam monitors the response to first- and second-line regimens and profiles drug resistance and HIV-1 variability during a 12 months follow-up. Specifically, the study evaluates the rate of immune-virologic failure at enrolment, month 6 and month 12; acquired mutations associated with drug resistance; HIV-1 subtype distribution; genetic variability in circulating (plasma) versus archived (cellular) viral strains; and early warning indicators of HIV drug resistance. Survival analysis will be performed during the 12 months follow-up. Primary outcomes are rates of virological failure, acquired HIVDR, and mortality.
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 Fokam expects that the findings will provide evidence-based recommendations to ensure a successful transition from paediatrics to adult ART regimens. Secondly, the results will highlight further needs of active ART combinations to achieve reduced morbidity and mortality in populations of adolescents living with HIV in sub-Saharan Africa. Without a successful transition of adolescents, the success rate of paediatric ART might be quickly jeopardised, with possible HIV-1 drug-resistance emergence, especially after years of paediatric ART exposure.
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