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

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Bringing antiretroviral drugs to children

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

The challenge

For several years Dr Kakolwa has been involved in clinical trials at the Ifakara Health Institute in Tanzania. Her fellowship at the pharmaceutical company GSK gave her the opportunity to develop her technical and practical skills in clinical trial management. The challenge integral to the clinical R&D Fellowships is for the fellows to then apply and share these advanced skills at their home institutions.

Dr Kakolwa’s career in research started when she joined the Ifakara Health Institute in Tanzania as a study coordinator of a malaria-in-pregnancy clinical trial (2010-2013). After the MiP study, she joined a second trial which assessed the clinical safety of the dihydroartemisinin-piperaquine (Euratersim^®) in the general population (2013-2014). In both trials, she had similar roles of coordinating clinical activities and many other tasks including such as data quality control, making sure lab procedures and sample collection followed GCP, SAE assessment and reporting, and attending investigators meetings. In 2014, she was involved in the therapeutic and efficacy studies of antimalarials as a sub-PI. In 2016, she joined a Focal Screening and Treatment (FSAT) group (Entomology) as a supervisor of the clinical team, a study which aimed at reducing malaria transmission in the Coastal region of Tanzania.

At GSK, her activities have immersed her in all aspects of clinical R&D across the product development timeline. Topics explored during the training were many, including:

Clinical product development: understanding clinical product development plans (including life cycle management activities such as post-market activities, regulatory aspects and pathways of drug registrations) and preparation of such a plan (phases I-IV, with focus on phase I) as well as evaluation of pre-clinical information (pharmacology, pharmacokinetics, toxicology, quality) relating to small molecule and biological investigational medicinal products (IMPs). This also includes identifying risks in the preclinical package of new small molecules or biological IMPs and devising a risk mitigation plan, its application in the protocol development, trial design and procedures and choosing suitable facilities to carry out such studies with minimal risks.

Clinical trial management with topics such as study designs, concepts, protocols development and case report form design, study implementation, data management and financial management. The fellowship offered opportunities to participate in or observe meetings of safety review teams for on-going clinical studies and participate in phase I/II clinical trials.

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.

The activities Dr Kakolwa is involved in after the training phase at GSK, are targeted to transfer clinical trial management skills and knowledge. She will also contribute to maintaining trial safety and quality control and be involved in writing systematic reviews and grant proposals.

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