"I had a terrible headache. It went on for hours; then hours became days, weeks and months. I took over-the-counter pills to no avail," says Patrick, a 50-year-old from Malawi.
What he was experiencing was not malaria, but the first symptoms of cryptococcal meningitis, a fungal infection of the lining of the brain and spinal cord and one of the leading causes of death among people living with HIV.
The treatment most commonly used in low-income countries only saves three out of every ten people who receive it, a mortality rate comparable to that of Ebola. A more effective alternative, amphotericin B, has its own downsides —its classical formulation is known as 'amphoterrible' for its life-threatening side effects and it requires in-patient monitoring in large hospitals. Patrick participated in the clinical trial of a safer, more effective regimen that saved his life. Yet, new regimens are not reaching all the people who need them.
"When I was sick, I could not help my family or contribute to the economy of my country. I am now back on my feet, and so could be many other people living with HIV if we only made testing and treatment of opportunistic infections available to them," says Patrick.
Flucytosine can cut deaths from cryptococcal meningitis from 70 to 25-30 percent compared to the regimen that is most commonly used in sub-Saharan Africa (i.e. fluconazole monotherapy.)
This antifungal has been around for 50 years, but it is still largely out of reach of people in low- and lower-middle-income countries. To date, there is only one main manufacturer.
"There is little supply and demand for flucytosine, it is expensive and it is not registered in any country in sub-Saharan Africa. With Unitaid's essential help, this medicine can be made widely available and significantly reduce deaths from HIV," says Professor Tom Harrison.
Harrison is professor of Infectious Diseases and Medicine at Saint George's University of London and researcher on cryptococcal meningitis.
The expert in new technologies
A package of new medicines and diagnostics holds promise of transforming the prevention and treatment of opportunistic infections, and reducing the death toll from HIV-related diseases, says Dr. Jennifer Cohn, senior director of Innovation and New Technologies at Elizabeth Glaser Pediatric AIDS Foundation (EGPAF).
“The use of new tools and models of care will show that managing advanced HIV is not only possible, but also essential to achieving epidemic control —and this realization will catalyze the required political will to ensure wider access to these products," she explains.
In addition to expanding access to better products, Dr. Cohn says, there is also a need to design models of care that decentralize and integrate screening and treatment of advanced HIV disease.
"We have to get patients with advanced HIV disease through this critical period so antiretrovirals can have the full positive impact we are promising the world," concludes Dr. Cohn.
Dr. Stephen Watiti is a doctor unlike any other. He treats people living with HIV, a virus he has himself. After surviving multidrug-resistant TB, cryptococcal meningitis and a form of cancer known as Kaposi's sarcoma, he became a front-line health advocate in his native country of Uganda for all people living with HIV.
"In Uganda, people may be diagnosed with advanced HIV disease, but the medicines are often unavailable or too expensive for them," says Dr. Watiti.
Guidelines for the management of advanced HIV disease "are the menu, not the food," says Dr. Watiti, who reiterates the urgent need to ensure that tests and medicines reach people.
"We need to detect advanced HIV disease earlier and treat opportunistic infections with the best regimens. Showing that patients can recover and be useful to society will also help fight stigma," he adds.
The man behind the national programme
South Africa is conducting the world’s largest national screening programme to detect cryptococcal infection before it causes meningitis. The fungus can be detected by dipping a test strip in leftover blood collected for CD4 cell testing, which looks at the strength of a person's immune system. People with a low CD4 count are at high risk of opportunistic infections.
South Africa is also implementing the entire package of health products and interventions recommended by WHO to prevent and manage advanced HIV disease, and hopes other countries can follow suit.
"We can now detect and treat cryptococcal disease earlier, preventing the development of meningitis. We know this saves lives and money, and we hope the programme expands to other countries in Africa and elsewhere," says Dr. Nelesh Govender.
Dr. Nelesh P. Govender is head of the Centre for Healthcare-Associated Infections, Antimicrobial Resistance and Mycoses at the South African National Institute for Communicable Diseases
"At MSF facilities everywhere in Africa we see people with advanced HIV disease due to treatment interruption or failure, stock-outs, barriers to adherence, late HIV testing and poor linkage to care," notes Florence Anam, HIV Advocacy Coordinator for Africa with Doctors Without Borders (MSF).
"People are still dying of HIV-related diseases, and these are unnecessary deaths because we now have the tools to prevent, diagnose and treat advanced HIV disease. We must focus on reducing deaths from HIV, and a great deal of this will be about expanding access to diagnostics and medicines," she says.