At the turn of the century, HIV was so rampant in Botswana that politicians and doctors viewed it as an existential threat. One in eight infants were reported to be infected at birth, while rates of mother to child transmission either through pregnancy, childbirth or breastfeeding ranged from between 20 and 40%, according to UNAIDS. Between 1990 and 2000, mortality among children under five almost doubled due to HIV.
With a population of just 1.7 million people, no cure available and the second-highest HIV prevalence in the world, the country’s then-president, Festus Mogae, declared in 2001: “We are threatened with extinction.”
“The situation was dire,” says Dr Loeto Mazhani, a now-retired paediatrician, public health official and academic at the University of Botswana.
“If your whole population was infected in utero, at birth or during early infancy, and the majority of them [were] either dying or living with significant disability, you could see there was no future.”
But out of this crisis would emerge one of the world’s most successful HIV-elimination programmes. Spearheaded by Mazhani, with backing from Mogae, a series of pioneering interventions were introduced which, over the course of two decades, slashed rates of mother-to-child transmission to just below 1%.
Earlier this year, Botswana was recognised as the first country in the world with a high HIV-burden to achieve the World Health Organization’s Gold Tier status for eliminating mother-to-child – or “vertical” – HIV transmission as a public health threat.
Dr Ava Avalos, an HIV specialist and technical adviser to Botswana’s health ministry, says the transformation was so drastic that the WHO initially refused to believe the figures that were coming out of the country.
“We would report that our birth numbers [of HIV infections] were so low, and they’d say, ‘No, no, you have 10,000 children that are [HIV] positive,’” she says.
“And this went on for years until they had to accept the fact that Botswana’s programme was as strong as we were saying.”
Today, new paediatric infections are so rare – with fewer than 100 HIV-positive infants born annually – that each case is subject to a thorough audit to understand how it happened.
Reaching this point required both significant political will, investment in scientific infrastructure and a sustained public health education programme to bring the latest science-backed strategies to those most at risk.
Mazhani recalls how one of the biggest challenges was convincing HIV-positive mothers to use formula milk rather than breastfeeding, due to the risks of transmission – something that went against conventional wisdom for infant nutrition.
“It meant that if a woman started getting formula milk, everyone in the community would know that she has HIV,” he says. “Mothers felt ostracised. But over time, that stigma of formula feeding slowly reduced.”
Roger Shapiro, a professor of immunology and infectious diseases at the Harvard TH Chan School of Public Health, has run an HIV research programme in Botswana since the 1990s. He says a particular turning point was the decision in 2013 to implement the WHO’s Option B+ strategy – making antiretroviral therapy that combined three drugs freely available to all pregnant and breastfeeding women living with HIV.
At the time, Botswana was one of the first countries in the world to fund Option B+ on a national scale. “It became clear that three-drug therapy was by far the best way to both treat mothers for their health, and essentially turn off vertical transmission,” says Shapiro.
Research, however, still indicated that these steps alone were not sufficient to completely prevent paediatric infections. Studies showed that a significant number of mother-to-child transmissions occurred when mothers unknowingly contracted HIV during pregnancy, with the unborn child becoming infected in the third trimester.
To eliminate these cases, Botswana’s health ministry invested in two laboratories in the north and south of the country capable of analysing thousands of PCR tests and began offering repeat HIV testing to all pregnant women.
According to Joseph Makhema, an internal medicine specialist who heads the Botswana Harvard Health Partnership, this enabled women who tested positive to be swiftly placed on antiretrovirals and post-exposure prophylaxis drugs to limit the possibility of transmission to the baby.
While other sub-Saharan African countries, notably Malawi, Rwanda, Zambia and Zimbabwe, now also offer widespread HIV testing for pregnant women, Shapiro says that Botswana’s programme is particularly effective because of the near-universal antenatal coverage in the country, with the vast majority of women accessing services and giving birth in hospital rather than at home.
Max Kapanda, who heads Botswana’s antiretroviral treatment programme, says: “This also allows all babies born to HIV-positive women to be immediately tested, and if infected, started on treatment as early as possible.”
Such is the success of this testing regime that there is now a unique group of children and adolescents with HIV in Botswana who are thought to have suppressed the virus to nearly negligible levels, having been on antiretroviral medications since birth.
At the recent International Aids Society conference in Rwanda, researchers discussed how these children are ideal candidates for experimental trials that attempt to use emerging treatments to cure them completely of HIV.
Makhema says: “We think that if you treat children early, you’re catching them before the virus has seeded through different bodily tissues or infected a particular type of immune cell called memory cells, and become encoded in the gene pool. So, hypothetically at least, it should be easier to cure these children.”
This theory is now being tested in a landmark clinical trial in Botswana, which will see about 30 children receive regular infusions of broadly neutralising antibodies or bNAbs, a new class of HIV drugs capable of attacking different strains of HIV and stimulating the immune system to recognise them, over the course of 11 months.
It is hoped that after this time period, a certain number of children will be able to live long-term without requiring any drug treatment at all, in effect rendering them cured.
“We’re hoping there’s two ways they could be cured,” says Shapiro, who is leading the trial. “They could either be cured because there’s no more intact virus left or because their immune system is able to handle the small amount that remains.”
While a cure has long been HIV researchers’ ultimate goal, the importance of such trials has taken on an even greater weight both in Botswana and more widely across sub-Saharan Africa in recent months in the wake of foreign aid cuts and economic turmoil.
While Botswana’s HIV programme has been more resilient than most – both antiretroviral treatment and testing has long been funded by the government – the country is experiencing an economic downturn and was initially facing 37% tariffs imposed by the Trump administration before they were cut to 15% last month.
“Botswana’s economy is very diamond-based,” says Avalos. “But there’s a lot now about the diamond industry which is challenging, with the rise of synthetic diamonds and the current situation with tariffs.
“It means our HIV programme is much more precarious. Previously if we ever had [treatment or testing] shortages, foreign partners would be able to assist us, but now those systems are not there.”
According to Makhema, it is unlikely that Botswana will be able to maintain its investment in HIV prevention and treatment over the long-term, making it all the more urgent to identify a strategy for curing infected individuals.
But given the country’s success in virtually eliminating mother-child transmissions, the availability of infrastructure required to support clinical trials, and a suitable population of children who may have the best chance of being cured, there is optimism that if a cure breakthrough can be achieved anywhere, it is most likely to happen in Botswana.
“If we can’t manage it here, I don’t know where we could do it,” says Avalos.
