South Africa is home to 7.8 million people living with HIV, with young women aged between 15 and 24 bearing the brunt of new infections.
Twenty-three years ago, 11-year-old Nkosi Johnson stepped onto the stage at the International Aids Conference in Durban, addressing an audience of 60 million. His words exposed the pain and stigma of the pandemic while showing extraordinary courage and belief in a better future.
Today, five baby boys from KwaZulu-Natal have continued Nkosi’s message of hope for an end to HIV. Their participation in a groundbreaking study, published in Nature Medicine in June, have given researchers a glimpse of what an HIV cure could look like during infancy.
After going without antiretroviral treatment for three to 10 months the babies, who were all born with HIV, were not ill nor did they have detectable levels of the virus in their blood.
Usually, when people (especially babies) stop taking their antiretrovirals (ARVs), they become seriously sick because the virus has free rein to weaken their immune systems.
The disease and treatment free state the babies achieved is also called “remission”. It means the virus is no longer causing problems in your body, but not necessarily that it has disappeared. Scientists can only determine that the virus is not lurking somewhere by testing people’s tissues after they’ve died, said the study’s lead author, Philip Goulder.
The five babies all had one thing in common: they were all boys, they were all infected with HIV in the womb, and they’d all been given antiretroviral treatment minutes after their first breath. Most infants start treatment in the first two days of life.
Scientists have long suspected the early HIV treatment for infants could lead to remission but the new study also reveals clues about why and how this happens. A crucial finding of the new research is that curing HIV in infants will probably look different for baby girls and boys and that getting ARV treatment immediately could be a part of it.
Here’s everything you need to know about the study and what it reveals about the virus that has evaded researchers for decades and still infects 150 000 people in South Africa every year.
How did researchers find the five boys?
From 2015 to 2023, the researchers enrolled 284 children who were infected with HIV in the womb in a study. The cohort was dubbed Ucwaningo Lwabantwana (which means “learning from children” in isiZulu).
It was observational research, which means that there was no intervention; researchers were simply watching what happens under usual circumstances. In other words, all the children in the study were subject to the same treatment protocols and got the same medicines as would any other child in the care of South Africa’s public sector.
Of the 284 children the researchers monitored, 25 were taking ARVs well enough for the virus to be undetectable in their blood by the time they reached their second birthday. It’s also called “viral suppression” and it means the person can no longer infect others.
There’s nothing unusual about this group. They were taking their medicine 90% of the time, so researchers weren’t surprised that they were virally suppressed. About 94% of people who take HIV treatment in South Africa are virally suppressed, shows household data presented at the International Aids Society conference in Germany in July.
Beyond the 25 typical virally suppressed babies, the five baby boys stood out because they were virally suppressed but they weren’t taking ARVs, and they hadn’t been for months.
Four of the five boys had gone without treatment for periods of three to 10 months. These mothers explained that for various social reasons, they weren’t able to keep collecting HIV medicine to give to their children, Goulder says.
The fifth baby hadn’t stopped getting medicine completely; instead he was given ARVs on and off for just under a year and a half.
The researchers are relatively sure that the children likely achieved viral suppression without treatment, because blood tests showed low or no sign of ARVs. Clinic records confirmed that their caregivers hadn’t been given HIV medicine in those months either.
Why were only boys cured?
There were more baby girls enrolled in the study than boys (60% were girls), yet only baby boys were cured. The reason for this has to do with the difference between the male and female immune systems, and how they interact with the mother’s immune system during pregnancy, Goulder explains.
Female foetuses have more of the immune fighter cells called “interferons” than males do right from conception. Interferons help to fight diseases by stopping a virus from replicating.
One would imagine that a strong immune system would be a good thing. But when it comes to HIV, female foetuses are instead at a disadvantage.
The reason is that the specific kind of interferons that are present in abundance can also make it easier for HIV to infect cells. These interferons can come with an increase in one of the proteins that HIV uses to enter cells.
Goulder and his colleagues ran immune system tests on mothers and their babies to understand what was happening.
What did the immune system test results show?
Consider a woman who is pregnant with twins, a boy and a girl (there were such instances in the Ucwaningo Lwabantwana cohort).
If the mother becomes infected with HIV and she doesn’t get treatment, the virus will be free to infect both babies.
Since the two foetuses have slightly different immune systems, the virus will have to launch subtly differing attacks to get around their defences.
In the case of the female foetus, the virus is met with a far fiercer offensive particularly from interferons. This pressure forces the virus to evolve into a version of itself that can survive the attack.
As a result, it’s a much meaner, tougher and, most importantly, interferon-resistant virus that infects the female foetus.
When the virus reaches the male foetus, his immune system isn’t yet able to use interferons to put up a fight, so the virus can infiltrate his cells easily without any interferon-specific defences.
But it’s not that the baby boy has no immune system at all, so even without the threat of interferons, the virus will still need to be able to replicate quickly enough to make sure it survives long enough to maintain an infection.
In most cases, baby boys will get infected by an HIV that is bad at blocking interferons, and good at making copies of itself.
In Goulder’s study, though, the baby boys who beat the virus had been infected with a strain of HIV that is bad at blocking interferons and bad at making copies of itself
Once the baby boy is born, his body begins to make interferons, which the virus can’t handle, and it’s also not able to replicate enough to maintain an infection. That means the virus circulating in the baby boy is toast.
The baby girl’s strain of HIV, on the other hand, will be specifically evolved to sidestep interferons, so her body will battle to clear the infection.
Why would such a weak virus survive to infect a male fetus?
The virus is always looking for the easiest way to survive the body’s defences. It does so by outsmarting the immune system, but the mutations can lead to trade-offs.
When the pregnant mother is infected, researchers think that the severe defence her body puts up forces the virus to change in a way that gets it into the body by any means, even if it means it’s no longer as good at making copies of itself.
“Ideally, the virus would like to be as fit as possible, but if it’s going to be transmitted it just has to take the hit and become a feeble virus.”
Once the virus is past the mother’s system, it will have to mutate again to infect the baby girl but will sail past the male twin’s defences largely unchanged.
The result is a form of the virus that the baby boys’ immune system can clear easily after he’s born.
Does this mean baby girls can’t be cured?
No. Infant boys up to the age of two seem to have a better chance at beating HIV into remission than girls of the same age, Goulder explains. But that benefit fades for boys by their second birthday.
Goulder’s previous research has shown that after the age of two, baby girls have a better shot at remission.
It’s not because of a change in the way their immune system works. Rather, it’s that the virus changes in a way that makes the female immune system’s strategy more effective, Goulder says.
Does this mean an HIV cure is around the corner?
No. This study is small and much more research will have to be done, Goulder says.
Scientists are looking into a range of cure options. Some of them try to attack the virus and others try to coax the body’s immune system to attack the virus and keep it out of someone’s system for good. HIV experts told Spotlight that a combination of approaches will likely be necessary to eliminate the virus completely.
What Goulder’s study does show, though, is that starting HIV treatment early (right after birth) in combination with other immune system therapies will likely be part of achieving remission in infants, and that infant cure will be different for males and females.
There’s a small group, such as these five babies, who may be able to beat HIV with regular ARVs under very specific circumstances.
What will happen next?
Goulder and his colleagues have already started work to set up a study to find more cases like the KwaZulu-Natal five. Some of the boys from the Ucwaningo Lwabantwana will be included, but one of the mother-baby pairs has already been lost-to-follow up.
Such research will include a step called “analytical treatment interruption” or ATI. This is a feature of HIV cure research in which scientists stop giving people antiretrovirals to see if the virus bounces back.
Researchers involved in ATI studies have a responsibility to make sure participants know about the risks that come along with stopping treatment. They’ll be more likely to infect others and more likely to develop both the mild and serious signs of untreated HIV. They might also become resistant to the HIV treatment they were using before ATI.
Community advocates have pushed for careful monitoring and support during this part of the study.
A study co-designed with community members found that people who agree to participate in ATI studies worry about their HIV medicine becoming ineffective, but their sense of contributing to a greater good fuelled their continued excitement and participation.
As for the KwaZulu-Natal babies, if they remain HIV and treatment-free until adolescence, it’s likely that researchers will study their immune systems once more to find out if the virus may still be hiding somewhere in their tissues.
This research is an important step toward the future Nkosi dreamed of, in which children no longer have to fight HIV and can get back to the playground. — Additional reporting by Joan van Dyk.
Tian Johnson is the founder and strategist of the pan-African health advocacy nonprofit, African Alliance.