Addressing the comorbidity challenge around TB in SA

Comorbidity refers to the presence of co-occurring infectious or chronic conditions in a person. In South Africa, the comorbidity of two serious infectious diseases, tuberculosis (TB) and HIV, is a major public health threat. This threat is exacerbated by a rise in non-communicable diseases such as diabetes. Both HIV and diabetes are risk factors for TB and contribute to the high mortality rate from TB in South Africa.

A further challenge in managing comorbidities is the risk of different treatments for the various conditions negatively impacting each other. Drugs need to be studied in the context of comorbidity to ensure they are safe and effective for these populations.

Researchers at the University of Cape Town (UCT) are working to address this co-morbidity challenge around TB.

TB and HIV

An estimated 7.8 million people in South Africa are living with HIV. People living with HIV are more susceptible to TB infection and, because TB affects the immune response to HIV, people living with HIV who contract TB are at higher risk for progression to advanced HIV. This makes for a particularly concerning comorbidity and is an important aspect in South Africa’s high mortality rate from TB.

 Work at UCT is being done on improving the diagnosis for TB in people living with HIV. This includes progress towards a new TB vaccine that is safe even in people with HIV and optimising treatment in patients with a TB-HIV comorbidity.

Dr Bianca Sossen from the Department of Medicine, worked with colleagues to test whether using urine, in addition to sputum, to diagnose TB in people with HIV could be a viable option. Because of severe illness and other factors people living with HIV sometimes struggle to produce sputum, that is commonly used for TB diagnosis. The current reliance on sputum testing for TB thus runs the risk of missed or late diagnosis of TB.

Dr Sossen and colleagues conducted a multi-country study of just under 1 800 people to test the efficacy of a urine-based TB test, Urine-Xpert Ultra, in people with HIV. The study found the urine test to be effective in diagnosing TB and recommended it be incorporated into standard testing for this population.

Professor Robert J Wilkinson of the Wellcome Discovery Research Platforms in Infection (CIDRI-Africa) and the Institute of Infectious Disease and Molecular Medicine, working with colleagues across South Africa, conducted a trial on a potential TB vaccine, M72 TB, building on the work of two earlier trials on the same vaccine.

Known as a phase two trial, MESA-TB focused on a larger population than the earlier phase one trials and showed the vaccine to be effective and safe. The main strength of this phase two trial was the inclusion only of people living with HIV in South Africa, a TB-endemic country. The data from the phase two trial contributed to the decision to include people with HIV in an ongoing phase three trial (Communi-TB), which, if successful, would form basis to submit for regulatory approval by drug regulatory authorities like the South African Health Products Regulatory Agency (SAHPRA).

If successful this vaccine could be introduced to complement the only other licensed TB vaccine, the Bacille Calmette-Guérin (BCG), which is given to infants in most parts of the world but offers minimal or no protection against pulmonary TB in adults or adolescents.

Dr Justin Shenje of the SA Tuberculosis Vaccine Initiative (SATVI) is working to ensure that people living with HIV can benefit from the latest breakthrough in TB treatment without a detrimental impact on their HIV anti-retroviral treatment (ART). A new four-month drug regimen for TB has been able to effectively reduce the duration of TB treatment by about 35%. However, this breakthrough regimen has been shown to reduce concentration of the highly effective anti-retroviral drug, dolutegravir, in the blood stream of people living with HIV. This raises concerns of a detrimental effect on long-term viral suppression of people with the TB-HIV co-morbidity.

To further investigate this, Dr Shenje and colleagues are working on a study in which they test giving the anti-retroviral dolutegravir twice a day, along with the new TB treatment regimen. The aim is to see if this combination will allow people with HIV to benefit from the new treatment without any risk and contribute to a reduction in mortality of people living with this co-morbidity.

TB and diabetes

People with diabetes have a threefold increased chance of developing TB and dying from it, compared to people without. In South Africa, TB and diabetes comorbidity is already a severe burden. Diabetes primarily affects older adults, and a 2022 study showed that in South Africans over 50 years, the rate of diabetes is around 40%. While TB prevention treatments do exist, there is currently not enough evidence that the benefits outweigh the risks when it comes to TB prevention for people with diabetes.

Professor Molebogeng Rangaka, an Honorary Professor in the School of Public Health is leading a trial testing whether a short-duration TB preventive treatment is safe and effective for people with diabetes, with a favourable benefit-risk balance.

The trial, Benefit-risk of TB prevention for people with diabetes (BALANCE), will be testing a one-month TB preventive treatment known as 1HP which has been shown to prevent TB disease in people living with HIV and has fewer side effects than the longer TB preventive treatment.

This one-month treatment could potentially be used in place of the current six-to-nine-month TB preventive treatment which is not recommended for people with diabetes as it is unclear if the risks outweigh the benefits.

BALANCE, which will be based in South Africa and the Philippines, will run for five years and recruit 3 100 people with diabetes older than 15 years.

Read part I in our World TB Day article series:  Tackling the challenges of TB in South Africa.