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

Twenty years ago antiretroviral medicines for HIV were a rare luxury in South Africa. Exorbitant costs and president Thabo Mbeki’s government fierce government opposition against providing antiretroviral treatment (ART) kept it out of the public sector. Those were terrible days. Many lives were lost.

By Dr Gilles Van Cutsem

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 outside of Cape Town, the clinics were quickly flooded with very ill people. Many were extremely weak; some had to be carried on relative’s backs or in wheelbarrows – haunting experiences.

But there was new hope. As patients were getting better on treatment, more people living with HIV demanded 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 ART 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.

HIV linked deaths decreased from 150,000 in 2000 – peaking at around 300,000 in 2006 – to 72,000 in 2019. But deaths have not decreased as much as it was hoped and HIV remains a leading cause of death in South Africa.

Globally 770,000 people died from HIV in 2019 indicating we are very far from the end of Aids.

Many people still present to health services with advanced HIV disease and Aids remains a major contributor to hospitalisations and deaths in Africa. MSF-supported hospitals in South Africa, Guinea, the Democratic Republic of Congo (DRC), Malawi and the Central African Republic continue to treat large numbers of people with Aids. Because people present with very advanced HIV disease, up to one in three dies during their hospital stay.

Why Aids hasn’t disappeared and what to do now:

The Test & Treat approach and the UNAIDS 90-90-90 targets (90% of people with HIV to know their status, 90% of those with their status known are on antiretroviral therapy and 90% of those on antiretrovirals have an undetectable viral load) have focused efforts to diagnose people with HIV and starting them on treatment.

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 to develop drug resistance.

Today, the majority of 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 focusing on the needs of patients returning to care or those failing treatment.  Stigmatisation and blaming patients for interrupting or failing treatment is common. This leads to delays in seeking treatment, and patients presenting as false-naïve (i.e. patients retesting for HIV and hiding that they were on treatment). This in turn leads to patients presenting in more advanced stages of the disease and/or inadequate treatment.

What is killing people with HIV?

We know that TB is the leading cause of death among people with HIV in resource-limited settings and is estimated to be responsible for up to 50% of deaths. Less known are cryptococcal meningitis, 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.

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 and decreasing 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.

No time to lose

To prevent death from advanced HIV, it is necessary to detect it earlier, 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 are life-saving.

Advanced HIV disease is defined by the World Health Organisation as having a CD4 count lower than 200 and/or having clinical stage 3 or 4 defining illnesses. Testing for CD4 ushers in rapid tests to detect two major killers of people with HIV: urinary lipoarabinomannan (LAM) for TB and serum cryptococcal antigen lateral flow assay (CrAg) for cryptococcal meningitis.

The CD4-CrAg-LAM triad is the basic diagnostic component of the Advanced HIV Package of Care. A CD4 count below 200 leads to systematic TB LAM and CrAg tests, regardless of symptoms. When infection with TB or cryptococcus is diagnosed at an early stage, before symptoms develop, they are easier to cure.

While TB (and even drug-resistant TB) treatment is readily available in most settings, flucytosine, amphotericin B and fluconazole – key drugs to treat and prevent cryptococcal meningitis – are not.

When left untreated, the odds of surviving cryptococcal meningitis are zero. Treatment with flucytosine and amphotericin B reduces mortality by 40% compared to fluconazole alone. Yet, in Africa, less than one in 150 patients in need had access to this drug in 2020, which still isn’t registered in most African countries.

What we need urgently to save lives is a rapid availability of 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.

Gilles Van Cutsem is a senior HIV & TB adviser for Doctors Without Borders (MSF) attached to the MSF  Southern African Medical Unit.

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