Essential research on tuberculosis and HIV cancelled. Clinical trial participants in limbo. Young researchers’ careers halted  – and billions of dollars invested and expertise developed over 30 years potentially down the drain.

These are some of the impacts on South Africa of the decision by the National Institutes of Health (NIH) barely a week ago to prohibit United States scientists from working with foreign researchers via “subawards”, leading to the immediate and mass cancellation of such grants with South African institutions.

At least 39 TB and HIV clinical research sites in South Africa are under threat due to NIH funding cuts, jeopardising at least 27 HIV trials and 20 TB trials, according to an analysis by the Treatment Action Group (TAG) and Médecins Sans Frontières (MSF) drawn mostly from the NIH’s Division of AIDS (DAIDS) presented at a media briefing on Thursday.

TB trials at risk include testing potential vaccines and new drugs; shorter, safer regimens, and the best treatment for TB meningitis. 

The HIV trials at risk include cure-related treatments involving broadly neutralising antibodies (bNAbs); vaccines designed to prime the body to make bNAbs; the impact of hormone treatment on women with HIV and treatment options for pre-exposure prophylaxis to prevent HIV.

Many of these trials are global, with South Africans making up 30-50% of global trial participants and 50-90% of trials on interventions for children and pregnant women, said Lindsay McKenna, TAG’s TB project co-director.

She estimates that the average investment in each trial participant is $12,000 – potentially all wasted if the trials are discontinued, and some have been going for several years already.

For some 30 years, South African clinical studies have provided global guidance on issues including prevention of mother-to-child HIV infection, when to start children on antiretroviral treatment, how to simultaneously treat TB and HIV, as well as the safety of HIV and TB treatments. Meanwhile, operational research, such task-shifting from HIV doctors to nurses, has led to more efficiency and cost-cutting.

“NIH funding is not aid. It’s competitive funding that researchers here competed for that went through stringent NIH processes and committees,” stresses Marcus Low, an epidemiologist and editor.

The NIH cuts come on top of the cancellation of grants from the US Agency for International Development (USAID) and US Centers for Disease Control (CDC) – primarily for HIV and TB programmes.

Impact on institutions

“South African academic and research institutes could lose about 30% of their annual income and may be forced to lay off hundreds of staff as a result of US funding cuts,” the analysis notes.

It warns of “the potential collapse of TB and HIV research and development capacity” in the country, with global impact in light of “ the substantial contributions of South African research centres to advancements in TB and HIV prevention, treatment, and care worldwide.”

Professor Ntobeko Ntusi, head of the South African Medical Research Council (SAMRC), told the media briefing that the country had been disproportionately affected both because of its high burden of HIV and TB and the excellence of its scientific community – making it a preferred site for research.

“Universities are now beginning retrenchments at scale,” said Ntusi, adding that affected scientists also provide postgraduate training.

“Hundreds of master’s, doctoral and post-doctoral fellows, whose stipends and research costs are dependent on these grants, find themselves in a position of inordinate precarity,” said Ntusi.

‘Ethical nightmare’

Prof Ian Sanne, co-principal investigator of the Wits HIV Research Group Clinical Trials Unit, describes navigating the US funding cuts as a “major regulatory and ethics nightmare”.

NIH investment in South African HIV and TB research “amounts to almost $2 billion over 20 years”, according to Sanne. His institution alone, Wits University in Johannesburg, stands to lose $150 million to $180 million in NIH funding.

As co-chair of Wits University’s ethics committee, Sanne has had to work with units on contingency plans for both staff and trial participants – despite US funds being terminated with immediate effect with nothing left over to wind down processes.

“In one of the studies in KwaZulu-Natal, the sponsor, USAID, stopped funding overnight and the microbicide rings that were under research with the participants were terminated without their knowledge,” said Sanne, leading to “a real ethical problem”.

Microbicide rings impregnated with ARVs are inserted vaginally to prevent HIV and studies often involve women at high risk of HIV infection.

Sanne’s unit lost US funding with immediate effect on 21 March – but it then had to embark on retrenchment procedures in terms of South African law, draining the reserves of the unit.

Expertise and infrastructure lost

Prof Linda-Gail Bekker, director of the Desmond Tutu HIV Centre at the University of Cape Town, says her centre will lose $6.9 million out of $10 million in NIH funds.

Earlier in the year, the centre lost a HIV vaccine grant worth $45 million over five years from USAID that would have seen five trials in eight southern African countries “contributing to the global quest to find an effective HIV vaccine”, she added.

The centre employs 400 people and will have to retrench “one-third to half our workforce”, said Bekker, whose groundbreaking research on a twice-yearly injection to prevent HIV infection earned her a standing ovation at the International AIDS Conference in Munch last year.

“We have an incredible critical mass of very experienced and very well-established research organisations in the country, and the infrastructure that has been built over the last 30 years has established an extraordinary clinical trial infrastructure,” said Bekker.

South Africa was able to use this expertise and infrastructure during the COVID-19 pandemic to “pivot to test at great speed, new COVID-related vaccines”.

“Throughout the years, we have contributed to creating new knowledge that is often [Investigational New Drug] related studies… that feeds into important guidance, such as the WHO guidance.”

Impact on other African countries

Dr Tom Ellman, director of MSF’s Southern Africa Medical Unit, said that MSF has applied the “pragmatic” HIV and TB research generated in South Africa in resource-poor settings throughout the continent.

Recently back from the Democratic Republic of Congo (DRC), Ellman said it was able to draw on the “self-managed, fixed-combination antiretroviral treatment regimen” developed in South Africa for people living with HIV in the conflict zone in South Kivu.

MSF’s large HIV programme in Kinshasa relies on dolutegravir – “a basic, simple, effective drug enabled by South African research”, said Ellman, who listed several other drugs that had been trialled in South Africa before hitting the global market.

“The best science leads to impact in the most difficult settings. There’s no question that South African science has transformed access to HIV, TB and other disease responses across Africa and across the world.”

Ellman said the funds cut is “particularly awful”  as “we are closer than ever to finding ways out of the HIV, TB and malaria pandemics”.

Appeal for support

TAG, MSF and the SAMRC have appealed for “alternative funds to sustain TB and HIV research in South Africa”.

Ntusi says numerous donors and governments have offered support and solidarity – but most wish to remain anonymous at present.

The researchers all agreed that the most urgent need is to provide immediate support to clinical research sites to ensure continuity of care and follow-up for study participants. 

“South African trial participants must be supported to complete treatments safely and, in cases of treatment failure, be offered appropriate alternatives, and research sites must be supported to complete data collection and analysis,” said TAG and MSF.

Image Credits: Paul Kamau/ DNDi, IAS.