In January, global health foundation Unitaid announced it was investing US$20 million in measures to avert preventable deaths among people with advanced HIV.

There are approximately 1 million HIV-related deaths annually.  Unitaid’s initiative aims to widen access to WHO-recommended drugs and tests for people living with HIV, whose immune systems are so weakened that they are vulnerable to life-threatening infections.

The work of two St George’s researchers working in the Centre for Global Health over several years proved instrumental in Unitaid’s decision to invest in this field.  

Dr Angela Loyse from our Global Health team began to lobby Unitaid in 2016 and has been in ongoing discussions since to take action on treatments for cryptococal meningitis, which is one of the major killers among patients with advanced HIV, accounting for more than 180,000 deaths a year. Dr Loyse is the chair of the Cryptcoccal Meningitis Action Group (cryptoMAG) and over the last 5 years has helped build and lead an informal network of researchers in Europe, the United States and Africa, implementing partners such as Médecins sans Frontières (MSF) and Elizabeth Paediatric Glaser Foundation (EGPAF), World Health Organisation (WHO), Center for Disease Prevention (CDC) finding a common position from all that action needed to be taken urgently on the provision of medicines, particularly flucytosine.

Professor Tom Harrison has been leading international multi-centre research trials exploring the best treatment for cryptococcal meningitis in resource-limited settings together with Drs Tihana Bicanic, Sile Molloy and Angela Loyse.    Fluconazole monotherapy is the most widely used and available treatment, but in the face of unacceptably high death rates, Professor Harrison’s team trialed two new strategies: Short course amphotericin B and flucytosine, and  a purely oral combination of fluconazole and flucytosine, both of which showed promising results.

Professor Tom Harrison’s ACTA trial results, published in March last year in the New England Journal of Medicine, demonstrated conclusively that a short course of amphotericin B in combination with flucytosine significantly reduced deaths and should be the first line treatment option for cryptococcal meningitis in resource limited settings, rather than existing longer more toxic amphotericin B treatments. The WHO immediately updated its guidelines to incorporate this research as its new preferred treatment option.

However flucytosine itself remains inaccessible in low and middle-income countries (LMICs) and prices remain out of reach.

Dr Loyse hadn’t given up on her lobbying work. In October 2018 Lancet Infectious Diseases published a piece written by her urging improved access for flucytosine and amphotericin B. The piece; ‘Leave no one behind’ featured Dr Loyse’s coalition of over 50 African research leads and clinicians, ministries of health (MOH) and additional members of cryptoMAG as co-authors, and called for urgent action to ensure access to flucytosine and amphotericin B in LMICs, discussing the ‘persistent and unacceptable high mortality of people with advanced HIV disease’.

At the same time Dr Loyse’s DREAMM project in Africa hosted a Unitaid representative who came to see the effect the project was having on reducing HIV-related meningo-encephalitis mortality in Tanzania, Cameroon and Malawi.   DREAMM is an implementation project that provides access to and training on rapid diagnostic tests and treatments for HIV-related meningo-encephalitis, including the results of the ACTA trial, in routine resource limited LMIC settings.

In January 2019 Unitaid’s announcement declared that its $20 million grant “will help make new, WHO-recommended medicines and testing tools affordable and available in lower income countries.”

Our role in Unitaid’s US$20m grant

As a key component, based on the ACTA trial results, they will make cheap generic flucytosine available in Africa through a deal with generic pharmaceutical manufacturers to buy an initial quantity of the drug to treat thousands of patients.  

Unitaid’s publicity campaign, facilitated in part by Dr Loyse, features Professor Harrison discussing flucytosine with the words; “With Unitaid’s essential help, this medicine can be made widely available and significantly reduce deaths from HIV”, and the testimony of an ACTA trial participant from Malawi, now leading a full and active life thanks to the improved treatment he received.

Dr Loyse said: “I am delighted that Unitaid have launched this important project to focus much-needed resources on reducing preventable and unacceptable HIV-related deaths; and very excited to have been chosen to work in 7 African countries with their implementing partner, the Clinton Health Access Initiative, as a strategic advisor.’ 

For more please see https://unitaid.org/advanced-hiv-disease/#en