Leading the way to an HIV cure
- Deryn Graham
The battle to save millions of HIV-positive lives bears fruit in unexpected ways.
When the business, commerce, and manufacturing sectors in South Africa were all forced to ‘pivot’ during the Covid-19 pandemic and find new ways to ensure their business sustainability, so too were our health scientists, who took time off of their decades-long intensive research into HIV, immunology and virology, to tackle the latest health threat.
But while their focus shifted from what was once South Africa’s leading causes of death, it was just these expertise, from some of the world’s leading specialists in the field, that helped the country become one of the leaders in the fight against the Covid-19 pandemic.
“The labs, expertise and knowledge that we have developed in South Africa in our work on HIV was invaluable in our preparedness for the pandemic,” says Glenda Gray, Research Professor in the School of Clinical Medicine at Wits.
“Without the clinical infrastructure and the work on neutralisation that our researchers have been doing around HIV, South Africa would not have been able to run the vaccine trials and respond in the way that we did.”
Now, however, the HIV focus is back on track, and the work that the country’s specialists are doing is paying off directly in fighting the human immunodeficiency virus at which it is directed. The tide in the thirty-year battle against HIV has finally turned in South Africa.
From a country that was once simply “the one with the largest population of HIV infected people in the world”, through the denialism years in 1999 to 2008, to rolling out the most extensive treatment programme globally, we have finally taken matters into our own hands.
“South Africa is taking the lead in HIV vaccine trials, implementation science, and different ways to deliver antiretroviral drugs,” says Professor Lynn Morris, Deputy Vice-Chancellor: Research and Innovation at Wits, whose work Gray cites as part of the Covid-19 pivot.
Treatment vs cure
Local money is being put into the search for a ‘cure’ for HIV and into finding a vaccine for a virus that Gray describes as one of the most difficult to crack. A functional cure has in fact been demonstrated in a number of patients worldwide, with Wits scientists being deeply involved in the study group of international researchers who were responsible for the third patient that was cured of HIV.
The so-called ‘Düsseldorf patient’ followed successes in Berlin and London. What the patients had in common apart from being HIV positive, was that all three had leukaemia [blood cancer]. They each underwent a stem cell transplant from a donor known to have a genome mutation in the HIV-1 co-receptor, CCR5 that makes cells resistant to HIV.
After receiving the transplant, patients remained for a time on antiretrovirals (ARVs) but after a period that differed in each case, were finally taken off this medication and the HIV remained supressed and undetectable. The goal of a functional cure is to render HIV unable to replicate so that the carrier no longer transmits the virus to others, and this is what was achieved in each of these cases.
At the International Aids Society Conference on HIV Science held in July 2023 in Brisbane, a new patient, the so-called ‘Geneva patient’ was revealed to have been ‘cured’ in the same way, but this time by a donor who did not have the CCR5 mutation.
“While these results are exciting, they do not represent a scalable cure for people with HIV,” says Dr Annemarie Wensing of Ezintsha, a division of the Wits Health Consortium, who, along with her colleague Dr Monique Nijhuis from the HIV Pathogenesis Research Unit at Wits was part of the Düsseldorf study. “Stem cell transplants leave patients extremely vulnerable with no immunity whatsoever for a period of time, making the procedure very dangerous,” says Wensing.
But in terms of HIV treatment, much the same as with cancer, putting patients into remission is almost as good as a cure. For now, the ARV drugs on the market are also able to achieve this.
Finding a vaccine
“Staying ahead of a virus that mutates at an incredible rate like HIV is a major challenge,” says Morris. “It means vaccines needs to keep changing too.”
Another major obstacle is that HIV integrates itself into the DNA of our T-cells, so vaccines need to block every single virus particle from infecting a cell by making sure that they stimulate the right kinds of immune responses.
“Traditional vaccines that produce antibodies to fight off a disease have proven ineffectual against HIV. So far, all the efficacy trials of HIV vaccines have been disappointing,” she says. “One of the biggest challenges of our times is how to make a vaccine that produces neutralising antibodies against the HIV envelope protein, but there are some encouraging new approaches including mRNA [messenger RNA] that proved so successful with Covid-19.”
Prevention better than cure
The adage ‘prevention is better than cure’ has never been truer than with HIV. Behaviour amongst young, sexually active females continues to pose a risk of exposure to HIV, but if government is able to ramp up its 95/95/95 by 2025 programme, which lost some ground during the Covid-19 pandemic, we may be able to slow the rate of new infections down.
The 95/95/95 programme targets seek to ensure that 95% of people living with HIV know their status and that, of these, 95% receive ARVs. Of those on treatment, the aim is to achieve a level of 95% with an undetectable viral load, reducing the risk of transmission to zero. Currently we are sitting on 94/77/92.
Morris believes that what ARVs have already achieved in South Africa is remarkable. “The fact is there is an entire cohort of people living with HIV and who are on ARVs. They are living long and healthy lives. Indeed, they are living longer and healthier than many other people, as they have learned to take better care of themselves,” she says.
New drug regimens have been shown to prevent HIV infection, including daily pills for pre-exposure prophylaxis (PrEP), the use of neutralising antibodies as passive immunity, and a bi-monthly injection of a long-acting ARV, CAB-LA, have all been trialled in South Africa.
There are local investors and financial and medical resources at our disposal in South Africa, but in terms of commercial viability, Morris believes that we need more incentives for pharmaceutical companies specifically. In business, these are known as ‘off-take agreements’ – pre-orders or commitments to purchase – but it appears that government has neither the budget nor political will in this case.
The country’s inadequate public health system remains a barrier to achieving better results in dealing with HIV. Both Gray and Morris are excited for the future of HIV research and the eventual eradication of the virus through vaccination, immunotherapy treatment or a possible cure, but they are cautious about the South African health system’s capacity to implement potential new protocols.
“Our health system is fragile, and we saw a number of slippages as a result of Covid-19,” says Gray.
However, there is certainly a great deal to be hopeful about in the search for a solution to HIV. Gray says, “South Africa has some of the world’s leading medical researchers in HIV. The country – and Wits – are open for business when it comes to investment in new technologies, new medicines, and new treatments for the virus.”
Any work done on HIV can also benefit research on other viruses, which may or may not already exist as was shown with Covid-19. Gray underlines the importance of the work that Wits is doing on HIV for other medical fields, including cancer research.
Every victory against HIV, every step forward in the search for more effective treatments and preventative medicines, takes us closer to discoveries in other fields.
“Any investment in HIV and immunology research is an investment into the future health of the country,” says Gray.
- Deryn Graham is a freelance writer.
- This article first appeared in Curiosity, a research magazine produced by Wits Communications and the Research Office.
- Read more in the 16th issue, themed: #Drugs, where we highlight the diversity, scope, and multi-dimensional nature of drug-related research at Wits University.