Why so many people still die from Aids-related illnesses despite more people being on treatment?

Twenty years ago antiretroviral medicines to treat HIV were a rare luxury in South Africa. The rich could buy them for tens of thousands of rands in the private sector. Most had no access to treatment at all. At the time, president Thabo Mbeki and his infamous minister of health Manto Tshabalala-Msimang were fiercely opposed to providing antiretroviral treatment in the public sector. Those were terrible days. Many lives were lost.
Today, one of the main challenges in the fight against Aids is the lack of availability of diagnostics and drugs that can help save lives of people suffering from advanced HIV; who are very vulnerable to deadly opportunistic infections such as tuberculosis, meningitis and severe bacterial infections.
When Doctors Without Borders (MSF) started treating people with antiretrovirals in Khayelitsha on the outskirts of Cape Town, the clinics were quickly flooded with very ill people. Many were extremely weak; some had to be carried on the back of relatives or in wheelbarrows – haunting experiences.
But there was new hope.
As patients were getting better on treatment, this hope emboldened people living with HIV to demand that the government respect their right to health. After four years of struggle – led by the Treatment Action Campaign – the government begrudgingly agreed to start providing antiretroviral treatment in 2004.
Antiretroviral coverage of people with HIV in South Africa has increased from 0% in 2000 to 71% in 2019, and the South African antiretroviral programme is now the largest in the world with more than five million people on treatment and increasing. The number of deaths from HIV has decreased from 150,000 in 2000 – peaking at around 300,000 in 2006 – to 72,000 in 2019. However, deaths have not decreased as much as it was hoped and HIV remains a leading cause of death in South Africa.
Why can't we stop the mortality? What are the gaps we can cover?
In the last ten years the focus has been on diagnosing people with HIV and starting them on treatment. Efforts around the test-and-treat approach have been mobilised around the UNAIDS 90-90-90 targets: 90% of people with HIV to know their status; 90% of those whose status is known to be on antiretroviral therapy; and 90% of those on antiretrovirals to have an undetectable viral load.
This is necessary but it is not enough to address HIV-related mortality. Life-long treatment requires life-long support. Some people will interrupt treatment; some will struggle to take their tablets every day, risking developing drug resistance and treatment failure.
Today, most people with advanced HIV either are failing or have interrupted treatment. In two MSF-supported studies in the DRC and Kenya, only 20%-35% of inpatients with advanced HIV were ART-naïve (had never accessed treatment) and over half of those on ART had treatment failure.
The reality of treatment interruption and treatment failure requires a new approach.
This is why MSF piloted Welcome Back Services in Khayelitsha, Cape Town. The services focus on the needs of patients returning to care and those failing treatment. Stigmatisation and blaming patients for interrupting or failing treatment is common. This leads to delays in seeking care, and patients presenting as false-naïve – patients retesting for HIV and hiding the fact that they were previously on treatment.
Also, Patients who present very late often have severe immune suppression, multiple concurrent life-threatening illnesses and significant organ damage due to HIV itself. Treatment is complicated by the need for many different medicines, with a higher risk of drug interactions and severe side effects. Even with intensive care, unavailable in most settings, many patients die.
TB is the leading cause of death among people with HIV in resource-limited settings. It is estimated that TB is responsible for around 50% of deaths. Two other leading causes are cryptococcal meningitis, which is responsible for one in five HIV deaths, and severe bacterial infections.
Together, these infectious diseases cause more than two thirds of HIV-related deaths. All three are preventable and treatable – if detected early enough.
Until recently, isoniazid taken for six to 36 months was the only widely available option for TB preventive treatment. New evidence showed that shorter regimens of rifapentine and isoniazid, weekly for three months or daily for one month, were equally effective at preventing TB – opening up new prospects of decreasing TB-related deaths.
Cotrimoxazole prophylaxis, given daily, protects against many of the most dangerous bacterial infections. Daily fluconazole can prevent cryptococcal meningitis and is recommended in some countries as primary prophylaxis, and everywhere as secondary prophylaxis, to prevent recurrent disease. However, it is missing in many – if not most – clinics in Africa.
When left untreated, the odds of surviving cryptococcal meningitis are zero. But cryptococcal meningitis can be prevented and there have been advances in treatment. Daily fluconazole is recommended in some countries for prevention of a first episode, and everywhere as secondary prophylaxis to prevent recurrent disease. Treatment with flucytosine and amphotericin B reduces mortality by 40%. Yet these medicines are still missing in many – if not most – health structures in Africa.
Steps can be taken to prevent death from advanced HIV. These include earlier detection at the primary care level – before patients develop disease so severe that they seek hospital admission. The longer the delay to diagnosis and treatment, the lower the chances of survival.
This is where CD4 tests and rapid tests for TB and cryptococcal meningitis are life-saving.
What is needed urgently to save lives is accelerated access to a package of care for the prevention, diagnosis and treatment of advanced HIV at the primary care and hospital level, along with strategies with clear targets to decrease AIDS mortality.
By Dr Gilles Van Cutsem, Senior HIV and TB Advisor, MSF Southern Africa Medical Unit.
South Africa