DNDi and our partners are working to improve access to optimal treatments for children and people with advanced HIV disease. Following the development of our 4-in-1 treatment for infants and young children living with HIV, DNDi is advancing the development of a sustained-release formulation of flucytosine for cryptococcal meningitis, a life-threatening fungal infection and leading cause of death in people with advanced HIV. We are also working with partners to address access barriers and encourage full adoption of current WHO-recommended tools and interventions for cryptococcal meningitis and advanced HIV.

Our progress in 2023 includes:

Translation

SR 5FC HIV (Cryptococcal meningitis): The second Phase I trial was completed at FARMOVS in Bloemfontein, South Africa in May 2023. The safety and pharmacokinetic data confirmed the dose of the identified sustained-release 5FC formulation, supporting the development of a twice-daily regimen for patients with cryptococcal meningitis. This sustained-release regimen (6 grams, administered twice per day) will be tested in a Phase II study in Tanzania and Malawi to determine its suitability as a substitute for the current immediate-release regimen of 5FC, which is administered four times per day. The study protocol was submitted to ethics committees and health authorities in the two countries and is expected to start in early 2024.

Implementation

Immediate-release flucytosine & liposomal amphotericin B access: DNDi and the HIV Policy Lab completed development of the Advanced HIV Disease (AHD) Dashboard,  an online resource that maps national guidelines for AHD and cryptococcal meningitis across 35 African countries. The dashboard serves to monitor progress and encourage countries to fast-track full adoption of life-saving interventions against AHD. It also aims to reduce the time lag between the generation of scientific evidence and adoption of revised policies by national health authorities. The AHD dashboard and an accompanying policy brief were launched at the 22nd International Conference on AIDS and STIs in Africa (ICASA) in December 2023.

4-in-1 (ABC/3TC/LPV/r) and other DAAs: Health authorities in the Democratic Republic of the Congo, Kenya, Mali, Mozambique, and Uganda approved and registered the 4-in-1 for use in their countries in 2023. US FDA approval remained pending. Under temporary use protocol, 39 children were initiated on treatment with the 4-in-1 in the North and South Ubangi provinces of the Democratic Republic of the Congo. 100% viral suppression at six months was achieved for the first nine children initiated on treatment. In South Africa, Cipla began distribution of the 4-in-1 for use when needed as an alternative to paediatric dolutegravir.

2-in-1 LPV/r pellets and ABC/3TC or AZT/3TC: The clinical study reports for the LIVING study conducted in Kenya, Uganda, and Tanzania were finalized in late 2023 for submission to the countries’ institutional review boards in February 2024.

Photo credit: Mamadou Diop-DNDi