TB preventive therapy supply constraints delay wider roll-out of shorter regimen

22 Mar 2023

South Africa’s recently published guidelines for the treatment of tuberculosis (TB) infection have been welcomed by several experts. The guidelines endorse the use of a three-month course of TB preventive therapy as opposed to the old six-month course. But, while the intention is to roll out the three-month course quite widely, supply constraints may delay things.

Though estimates vary substantially, it is thought that in the region of 300,000 people fall ill with tuberculosis (TB) in South Africa every year. Many more people, however, have TB bacteria in their lungs and do not fall ill — something referred to as latent TB infection. It is estimated that only about 5% to 15% of adults with latent TB infection go on to develop active TB disease — mostly within months of inhaling the TB bacteria, sometimes only years later.

While active TB disease is typically treated and cured with a combination of four different antibiotics, TB infection can be cured with only one or two. Such treatment of latent TB infection is called TB preventive therapy since it prevents the development of active TB disease.

TB preventive therapy is a critical component of the fight against TB, says Dr Louisa Dunn, provincial TB technical lead for Think TB (an NGO). “Not only does it protect individuals, but communities as well by limiting the transmission of TB,” she says.

Dr Liesbet Ohler, the medical referent for Médecins Sans Frontières (MSF) in Eshowe in KwaZulu-Natal, points out that South Africa’s most recent TB prevalence survey suggested that 390,000 people fell ill with TB in 2018.

“With the average household size being 3.3 people, this means that 897,000 people (and in all likelihood more, due to the impact of Covid-19 on TB services) were exposed to TB in the household and are in need of TB preventive therapy as an urgent intervention,” she says.

New guidelines

Spotlight has been hearing talk of new TB prevention guidelines for at least four years. Then, last month, South Africa’s new guidelines for the treatment of TB infection were finally published. The response from experts interviewed by Spotlight has almost universally been positive.

Commenting on the delays, Dunn says great care has been taken in the development of the new guidelines.

“Before the release of any new clinical guideline, it is essential to ensure that they are refined and perfected to suit the South African context and all infrastructure required to support them, such as stock availability and budgets are in place to ensure successful roll-out and scale-up,” she says.

She says the new guidelines will help reduce the TB burden in South Africa and identifies two reasons for this — greater access to TB preventive therapy in general and greater access to new shorter course preventive therapy regimens.

Shorter regimens

Though several short regimens are recommended in the guidelines, the most notable one is 3HP. This is a three-month regimen consisting of the drugs rifapentine and isoniazid taken weekly. By and large, 3HP is replacing the old regimen of isoniazid taken daily for six or more months.

The benefit of 3HP is it is a shorter course of treatment, Ohler says.

“Studies have shown it has higher completion rates, lower rates of toxicity, and is non-inferior compared to longer regimens of daily isoniazid. That means it is at least as effective. Currently, 3HP can be taken by adults and adolescents living with HIV, provided there are no contraindications such as pregnancy or an antiretroviral therapy regimen which is not suitable to be taken with it,” she says.

“In a nutshell,” says Dr Ntokozo Mzimela, a lecturer in integrated pathology at the Faculty of Health Sciences at Nelson Mandela University, “3HP is an effective, shorter, and less toxic regimen that leads to higher adherence than previous TB preventive therapy.”

But on the downside, says Ohler, there is no child-friendly 3HP formulation.

“There is another regimen, however, called 3HR, which is also given for three months but every day instead of once a week. 3HR comes in a child-friendly fixed-dose, dispersible tablet form, which means it can dissolve in water — it doesn’t have to be swallowed,” she says.

Supply constraints

3HP is not new in South Africa and Spotlight has previously reported on its use in some districts.

Dr Lindiwe Mvusi, Director of the TB Control and Management Cluster in the National Department of Health, says 3HP has been available since 2021 but availability has largely been limited to six Global Fund-supported districts due to supply constraints from the manufacturer. The districts are eThekwini, OR Tambo, Ehlanzeni, Ekurhuleni, Johannesburg, and Cape Town (with Cape Town only starting in 2023).

According to Mvusi, 43,557 people living with HIV have so far been provided with 3HP — 11,505 in Johannesburg, 12,922 in OR Tambo, 13,991 in eThekwini, 2,574 in Ehlanzeni, and 2,565 in Ekurhuleni.

Mvusi says the scale-up of 3HP to all provinces is planned for the 2023/24 financial year.

“The provinces are working on the roll-out plans, which will include capacity building for clinicians, strengthening adherence counselling, and demand creation through community and civil society engagements,” Mvusi says.

At this point, she says, they have not set targets due to uncertainty of supply.

“We have one global supplier currently which has limited production capacity,” she says. That single supplier is the pharmaceutical company Sanofi. Sanofi had not responded to questions from Spotlight by the time of publication.

The hope is that additional suppliers will be included in the next tender, which should increase supply and potentially lower prices due to competition.

“The request for bids was published last year and is closed now,” says Mvusi. She says the outcomes of the new tender are not yet out. Supply in terms of the new tender is anticipated to start in October this year.

South African Health Products Regulatory Authority (Sahpra) spokesperson Yuven Gounden confirmed to Spotlight that, in addition to the Sanofi product, rifapentine-containing products from generic manufacturer Macleods have also been registered by the regulator.

Asked what other rifapentine-containing products had been filed with Sahpra for registration, Gounden confirmed that there are additional products in the process, but did not provide details.

“Kindly note that we cannot disclose product-related information while the products are in the registration process,” he told Spotlight.

Spotlight could not establish whether Macleods or any companies other than Sanofi had submitted bids for the new tender. Macleods had not responded to questions from Spotlight by the time of publication.

Meanwhile, healthcare workers have been gaining experience in providing 3HP. Dunn says in KwaZulu-Natal, 3HP was first rolled out in eThekwini as a pilot district.

“This has led to the development of standardised registers and tools to support roll-out as well, and the experience has provided best practices that can be adopted in the rest of the province. Training of the remaining districts has been undertaken, stock is in place, and full roll-out across the province is imminent,” she says.

Wider eligibility

Apart from the changes in regimens, the new guidelines also make many more people eligible for TB preventive therapy.

Dunn explains that previous guidelines offered TB preventive therapy to only the most vulnerable groups — child contacts under five years of age and people living with HIV.

“The new guidelines have significantly widened access to include all individuals exposed to TB and all high-risk groups, for example, inmates in correctional facilities, healthcare workers, people on dialysis, people with silicosis, and people taking medications which can weaken the immune system and many more,” she says.

Mzimela is positive about the widening of access to TB preventive therapy.

“If more people are put on preventative treatment, it will reduce the number of new cases and our goal to meet the WHO End TB targets reducing morbidity and mortality in our communities related to TB infection can be met,” she says.

Another important change highlighted by Dunn is the introduction of a “test and treat” approach for TB.

“This means after identifying people who are exposed or at high risk for developing active TB disease, they should be tested for TB disease. Those with confirmed TB disease should be offered TB treatment, and those with TB disease ruled out should be offered treatment with TB preventive therapy,” she says. DM/MC

This article was published by Spotlight — health journalism in the public interest.

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South Africa

New guidelines

Shorter regimens

Supply constraints

Wider eligibility