EDCTP-supported HIV clinical research impacts
EDCTP supported the REMSTART trial under EDCTP1. This trial provided data supporting the July 2017 WHO guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy. REMSTART (Reduction of early mortality among HIV-infected subjects starting antiretroviral therapy: a randomised trial), which took place at sites in Zambia and Tanzania and was coordinated by Dr Saidi Egwaga, evaluated a health service strategy designed to reduce the high early mortality associated with antiretroviral therapy in Africa. A component of the strategy was an increased frequency of diagnostic testing for cryptococcal meningitis and TB. REMSTART demonstrated that all-cause mortality at 12 months was decreased in the intervention group when compared with the control group (in which participants were offered standard care). EDCTP continues to support investigation of this approach through our funding of the TRIP study (Translating Research Into Practice), led by Dr Sayoki Godfrey Mfinanga (National Institute for Medical Research, Tanzania). TRIP aims to determine the feasibility, cost-effectiveness, and impact of scaling up the REMSTART intervention in 12 urban and 6 rural settings in Tanzania.
Many people living with HIV are also affected by diseases such as TB, a co-infection which has been—and continues to be—well researched. However, not all HIV-related co-infections have received sufficient attention. Despite significant strides in HIV management, opportunistic infections are still a frequent cause of mortality in immunosuppressed people living with HIV. Due in part to the highly immunocompromised status of these patients, co-infections can result in unique diagnostic and treatment challenges. EDCTP has responded to this challenge through support for research on HIV-associated co-infections—especially cryptococcal infections—and has consulted widely with stakeholders in the field to guide our investments in this area. Currently, EDCTP-supported projects on HIV-associated co-infections include the DREAMM and the AMBITION projects.
The DREAMM project, led by Dr Angela Loyse (St. George’s University of London, UK), is a multi-centre study that aims to evaluate a semi-quantitative cryptococcal antigen lateral flow assay (CrAG LFA) called Biosynex crypto PS, developed by the Pasteur Institute (France). This test will enable the identification of HIV patients with high CrAg cryptococcal meningitis titres, who may benefit from more aggressive or prolonged antifungal therapy. The CrAg LFA test is embedded within an algorithm that aims to reduce time to diagnosis and time to initiation of effective treatment. DREAMM is taking place at sites in Cameroon, Malawi, and Tanzania, and includes partners from the National Institute for Medical Research – Tanzania, Lilongwe Medical Relief Trust Fund, the Central Hospital of Yaoundé (Cameroon), Institute Pasteur, and the Liverpool School of Tropical Medicine.
The AMBITION project, led by Dr Joseph Jarvis (London School of Hygiene & Tropical Medicine, UK) is funded by EDCTP and from the UK by MRC, DFID, and Wellcome Trust. AMBITION is a multi-centre phase-III trial to determine whether short-course high-dose liposomal amphotericin (L-AmB, Ambisome) is as effective as 14-day amphotericin B-based therapy in averting all-cause mortality in HIV-associated cryptococcal meningitis. Eight hundred and fifty patients will be recruited at 6 African partner-sites, making this the largest HIV-associated cryptococcal meningitis trial ever conducted. A novel short-course highly effective and safer L-AmB treatment regimen for cryptococcal meningitis would transform the management of late-stage HIV and markedly improve outcomes in HIV programmes in Africa. Project partners include the Liverpool School of Tropical Medicine, the University of Liverpool, St. George’s University of London, Institut Pasteur, Infectious Diseases Institute Limited, the Botswana-Harvard AIDS Institute Partnership, University of Cape Town, University of Zimbabwe, and Lilongwe Medical Relief Trust Fund.