Wellcome Investigator Award for CIDRI-Africa PI Prof. Gary Maartens
1 Aug 2018 - 10:00
Dolutegravir will soon replace medicines currently used for HIV in Africa as it is safer and less likely to cause viral resistance. However, additional research is needed to fill gaps in knowledge on the safe use of the drug by African people and people living with tuberculosis (TB); to date, major dolutegravir studies have included few Africans and excluded people with TB.
The Wellcome Trust has awarded Prof. Maartens funding to conduct a set of studies that will answer three critical questions about dolutegravir-based antiretroviral therapy in an African population.
First, what are the determinants of dolutegravir toxicity in Africans? Dolutegravir's safety appears to be related to its concentration in blood. More African than European people express a genetic variant which reduces the body’s capacity to break down the drug, which might increase the risk of toxicity. The research team will conduct pharmacokinetic and pharmacogenetic studies of participants enrolled in a randomised controlled trial being conducted in Johannesburg to answer this question.
Second, can standard dose dolutegravir be used in patients with tuberculosis? TB treatment enhances the breakdown of dolutegravir. Studies have shown that doubling the dose of dolutegravir can overcome this interaction, but this is impractical in programmatic settings. Building on preliminary data showing that standard dosing may be adequate with TB treatment, the team will conduct a randomised controlled trial of daily dolutegravir-containing treatment in HIV-positive patients on TB therapy.
Third, can dolutegravir be used in second-line antiretroviral therapy without first testing for viral resistance? A recent study has shown that dolutegravir is effective in second-line treatment when resistance to other medicines is known, but resistance testing is unaffordable in Africa. The team will conduct a pilot study of dolutegravir-containing treatment in participants who have experienced virologic failure on first-line treatment without a priori knowledge of resistance tests.
The results of these studies could inform public health policy on the use of dolutegravir.
The team includes Prof. Graeme Meintjes (UCT; CIDRI-Africa PI), Dr Andrew Hill (University of Liverpool), Dr Paolo Denti (UCT), Prof. David Haas (Vanderbilt University), Dr Phumla Sinxadi (UCT), and Prof. Francois Venter (University of the Witwatersrand).
Prof. Maartens heads the Division of Clinical Pharmacology in the Department of Medicine at UCT. His main research interests are in therapeutic aspects of HIV-associated TB, drug-resistant TB, and antiretroviral therapy in resource-limited settings. He has been involved in international guideline development for the management of HIV and TB for the World Health Organization and the Centers for Disease Control and Prevention. He serves on the Tuberculosis Transformative Science Group of the AIDS Clinical Trials Group (National Institutes of Health).
CIDRI-Africa congratulates Prof. Maartens on his award.