The Variant Hunters: Inside South Africa’s Effort to Stanch Dangerous Mutations

NTUZUMA, South Africa — A few months ago, Sizakele Mathe, a community health worker in this sprawling hillside township on the edge of the city of Durban, was notified by a clinic that a neighbor had stopped picking up her medication. It was a warning sign that she had likely stopped taking the antiretroviral tablet that suppresses her H.I.V. infection.

That was a threat to her own health — and, in the era of Covid-19, it might have posed a risk to everyone else’s. The clinic dispatched Ms. Mathe to climb a hill, wend her way down a narrow path and try to get the woman back on the pills.

Ms. Mathe, as cheerful as she is relentless, is part of a national door-to-door nagging campaign. It’s half of a sophisticated South African effort to stanch the emergence of new variants of the coronavirus, like Omicron, which was identified here and shook the world this past week.

The other half takes place at a state-of-the-art laboratory 25 miles down the road. At the KwaZulu-Natal Research Innovation and Sequencing Platform in Durban, scientists sequence the genomes of thousands of coronavirus samples each week. The KRISP lab, as it is known, is part of a national network of virus researchers that identified both the Beta and Omicron variants, drawing on expertise developed here during the region’s decades-long fight with H.I.V.

This combination of high tech and grassroots represents one of the front lines in the world’s battle against the evolving coronavirus. On Friday, the research network in South Africa reported to a world waiting anxiously for new information that the new variant appeared to spread twice as quickly as Delta, which had been considered the most contagious version of the virus.

The researchers at KRISP are global leaders in viral phylogenetics, the study of the evolutionary relationship between viruses. They track mutations in the coronavirus, identify hot spots of transmission and provide crucial data on who is infecting whom — which they deduce by tracking mutations in the virus across samples — to help tamp down the spread.

Since the start of the pandemic, they have been closely scrutinizing how the virus changes in South Africa because they are worried about one thing in particular: the eight million people in the country (13 percent of the population) who live with H.I.V.

When people with H.I.V. are prescribed an effective antiretroviral and take it consistently, their bodies almost completely suppress the virus. But if people with H.I.V. aren’t diagnosed, haven’t been prescribed treatment, or don’t, or can’t, take their medicines consistently each day, H.I.V. weakens their immune systems. And then, if they catch the coronavirus, it can take weeks or months before the new virus is cleared from their bodies.

When the coronavirus lives that long in their systems, it has the chance to mutate and mutate and mutate again. And, if they pass the mutated virus on, a new variant is in circulation.

“We have reasons to believe that some of the variants that are emerging in South Africa could potentially be associated directly with H.I.V.,” said Tulio de Oliveira, the principal investigator of the national genetic monitoring network.

In the first days of the pandemic, South Africa’s health authorities were braced for soaring death rates of people with H.I.V. “We were basically creating horror scenarios that Africa was going to be decimated,” said Salim Abdool Karim, an epidemiologist who heads the AIDS institute where KRISP is housed. “But none of that played out.” The main reason is that H.I.V. is most common among young people, while the coronavirus has hit older people hardest.

An H.I.V. infection makes a person about 1.7 times as likely to die of Covid — an elevated risk, but one that pales in comparison with the risk for people with diabetes, who are 30 times more likely to die. “Once we realized that this was the situation, we then began to understand that our real problems with H.I.V. in the midst of Covid was the prospect that severely immunocompromised people would lead to new variants,” Dr. Abdool Karim said.

Researchers at KRISP have shown that this has happened at least twice. Last year, they traced a virus sample to a 36-year-old woman with H.I.V. who was on an ineffective treatment regimen and who was not being helped to find drugs that she could tolerate. She took 216 days to clear the coronavirus from her system; in that time inside her body, the viruses acquired 32 different mutations.

In November, Dr. de Oliveira and his team traced a coronavirus sample with dozens of mutations to a different part of the country, the Western Cape, where another patient was also poorly adhering to the H.I.V. drug regimen. The coronavirus lingered in her body for months and produced dozens of mutations. When these women were prescribed effective drugs and counseled on how to take them properly, they cleared the virus quickly.

“We don’t have a lot of people like her,” Dr. Abdool Karim said of the woman who took 216 days to clear the coronavirus from her system. “But it doesn’t take a lot of people, it just takes one or two.” And a single variant can rattle the world, as Omicron has.

The origin of this variant is still unknown. People with H.I.V. are not the only ones whose systems can inadvertently give the coronavirus the chance to mutate: It can happen in anyone who is immunosuppressed, such as transplant patients and those undergoing cancer treatments.

By the time the KRISP team identified the second case of a person with H.I.V. producing coronavirus variants, there were more than a dozen reports of the same phenomenon in medical literature from other parts of the world.

Viruses mutate in people with healthy immune systems, too. The difference for people with H.I.V., or another immunosuppressing condition, is that because the virus stays in their systems so much longer, the natural selection process has more time to favor mutations that evade immunity. The typical replication period in a healthy person would be just a couple of weeks, instead of many months; fewer replications mean less opportunities for new mutations.

And because South Africa has so many people with H.I.V., and because this new pandemic has struck hard here, disrupting life in many ways, there is a particular urgency to the work of trying to block the variants.

That is where the efforts of community health workers such as Ms. Mathe come in. On a typical workday, she walks dirt paths past leaking standpipes and front-step hair salons, armed with an ancient cellphone and a mental roster of who has turned up at the clinic lately, who is looking unwell and who needs a visit. Ms. Mathe, who herself has been on H.I.V. treatment for 13 years, is paid $150 a month.

Silendile Mdunge, a thin 36-year-old mother of three, stopped taking her antiretrovirals during the brutal third wave of Covid that hit South Africa between May and July. Her drugs were no longer being delivered to a nearby community pickup point because many health care workers were redeployed. Instead she was supposed to collect the pills at a central clinic about nine miles away. But she feared contracting this new virus in a shared taxi or standing in the huge clinic lines that she heard about.

She was off the medication for four months before Ms. Mathe turned up at the small home built of scrap wood that Ms. Mdunge shares with seven family members.

“She told me that people who defaulted on their treatment are no longer living, she told me I must think of my children, she said I could die,” said Ms. Mdunge, leaning on the rough door frame in a warm, light rain. Those were things she already knew, in the abstract.

But the persistent presence of Ms. Mathe made the warnings difficult to ignore. With a shrug and an eye roll, Ms. Mdunge suggested that she restarted treatment to end the pestering as much as anything else.

Ms. Mathe listened to this recounting of her methods with a grin. “If you didn’t have love for people, you wouldn’t do this job,” she said

Of the eight million South Africans with H.I.V., 5.2 million are on treatment — but just two-thirds of that group are successfully suppressing the virus with medication. The problem extends beyond South Africa’s borders: 25 million people live with the virus across sub-Saharan Africa, of whom 17 million are virally suppressed with treatment.

The KRISP lab is sequencing coronavirus samples from across Africa, to fill some of the gaps for countries that do not have their own capacity to do so. South Africa’s surveillance network and genomic sequencing are comprehensive enough that its researchers may be first to detect even cases that do not originate in the country.

The great fear is a variant with “immune escape”: the ability to elude Covid vaccines or the immune response elicited by previous infection. As more and more people in South Africa get vaccinated against Covid, there is the potential for a variant to be brewing in the body of a vaccinated person.

“You have a situation where you’ve got the potential to create really nasty variants,” said Dr. Abdool Karim, who has helped lead South Africa’s Covid response. Previous variants emerged when few people had access to vaccination, but now South Africa has delivered the shot to more than a third of its citizens. If vaccinated people with H.I.V. don’t have or don’t take their antiretrovirals, there could be an opportunity for the virus to mutate to evade the vaccine.

“Now, many of these H.I.V. patients have been vaccinated so they have their immune responses. So, if they were to generate a new variant, that variant is going to have to escape those immune responses,” Dr. Abdool Karim said.

Dr. de Oliveira said he was worried less about a vaccine-resistant variant emerging in South Africa than, for example, a pocket of the United States with untreated H.I.V., low vaccination coverage and a weaker surveillance network than South Africa has.

“The chances are we’d find it first,” he said with a grim laugh.

The difference with the risk from mutating virus in people with uncontrolled H.I.V., he pointed out, is that it is a problem with a ready solution — getting everyone with the H.I.V. on treatment — whereas a transplant or cancer patient has no options.

Above all, the answer to ending the variant threat is to stifle coronavirus transmission. “Vaccinate, vaccinate, vaccinate the population of Africa,” he said. “My worry is the vaccine nationalism or the hoarding of the vaccine.” People with H.I.V. should be prioritized for vaccine boosters, to maximize the effectiveness of their immune responses, he added.

So far, South Africa’s efforts to tackle the variant issue, and be transparent about it, have come at a steep price, in the form of flight bans and global isolation.

“As scientists, especially in the kind of forefront, we debate playing down the H.I.V. problem,” Dr. de Oliveira mused in his lab last week. “If we are very vocal, we also risk, again, big discrimination and closing borders and economic measures. But, if you are not very vocal, we have unnecessary deaths.”

Carl Zimmer contributed reporting.

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