South Africa may be the last country in Africa to gain access to pediatric formulations of the antiretroviral drug dolutegravir as regulatory delays continue.
In 2019, South Africa introduced guidelines recommending treatment with dolutegravir for adults and children around six years and older, based on weight.
Three years later, however, the country still has not provided widespread access to dispersible and child-friendly formulations. Instead, doctors had to request access on a case-by-case basis. The country’s regulatory body, the South African Health Products Regulatory Authority (SAHPRA), must approve all drugs for use before they can be used in the country.
Although the recent SAHPRA approvals pave the way for generic manufacturers to start supplying the drug, they are not yet allowed to do so. The South African Department of Health is currently updating its treatment guidelines to ensure that where generic versions are available, they can be used even in very young children.
Clinicians say the rollout of dispersible dolutegravir is key to making HIV treatment once a day for South African children and improving outcomes. The change comes as some doctors report an increase in sight loss and malnutrition in children living with HIV.
“As clinicians, we want to make sure we have access to these drugs as quickly as possible,” says Moherndran Archary, a professor at the University of KwaZulu-Natal who specializes in pediatric infectious diseases. “As it stands, South Africa will probably be the last country in Africa to have access, and we are the largest supplier of pediatric antiretroviral drugs.”
Dispersible medications can be mixed with liquids such as water or juice. These formulations are crucial for children who may be too old for infant antiretroviral syrups but too young to swallow adult-size tablets. Without many dispersible antiretrovirals, children like this depend on large volumes of syrup several times a day.
Today, the non-profit organization Drugs for Neglected Diseases Initiative (DNDi) announced that SAHPRA has granted accelerated approval to a dispersible four-in-one combination of antiretrovirals abacavir, lamivudine, lopinavir and ritonavir for young people children living with HIV. Produced by pharmaceutical company Cipla, this sweet-tasting combination treat can be mixed into milk or water or sprinkled on foods such as porridge.
South Africa should also see increased access to a dispersible two-in-one of abacavir and lamivudine, which – if it could be combined with similarly formulated dolutegravir – would mean many children would finally be on treatment. once a day.
Around 300,000 children under the age of 15 are living with HIV in South Africa, according to 2021 government data. Just under half of these HIV-positive children are on treatment, and a similar percentage are virally suppressed – figures well lower than those seen in adults.
Patients rely on clinical access programs despite regulatory delays
Other African countries have introduced child-friendly dolutegravir faster, Archary says, as many are accepting World Health Organization (WHO) approval, also known as pre-qualification.
But South Africa requires drugs to be registered by SAHPRA and as part of this it needs companies that invent drugs to register products before generic applications can be processed, says Andy Gray, senior lecturer in pharmacology at the University of KwaZulu-Natal.
Gray explains that regulators like SAHPRA often depend on innovator companies — in the case of pediatric dolutegravir, ViiV Healthcare — to provide baseline data on a drug’s safety and effectiveness, even if they don’t have the intention to market a medicine in the country. Then, generic manufacturers must show that they meet these same standards.
SAHPRA approved ViiV Healthcare’s application on April 29. The drug regulator said it was reviewing two generic applications for pediatric dolutegravir, but did not say which companies made the applications. Still, two generic makers Mylan Laboratories and Macleods Pharmaceuticals hold voluntary licenses to manufacture and sell the drug, ViiV Healthcare spokesman Thomas Jenkins said.
Since 2018, ViiV Healthcare has partnered with the international non-profit organization Clinton Health Access Initiative (CHAI) and drug funding mechanism Unitaid to provide technical support to Mylan and Macleods to produce dolutegravir for children .
“We believe that through these partnerships, we will be able to enable greater access to dispersible dolutegravir 5mg for those who need it most and therefore do not plan to market the product in South Africa at this time,” said Jenkins.
He adds that ViiV Healthcare is supplying certain pediatric medicines on a patient-by-patient basis in South Africa under clinical access programs until generics can be registered.
Several measures underway to improve access to pediatric HIV treatment
Archary and other infectious disease experts from the Southern African HIV Clinicians Society released new guidelines on antiretroviral therapy in May. The society includes many leading HIV experts and periodically reviews the latest scientific evidence to make treatment recommendations. Their guidelines have consistently been adopted as best practice in the private sector in the region and have been a precursor to policy changes in the public sector, particularly in South Africa.
If adopted in South Africa, the company’s advice would allow almost all children around six years of age or older to be switched to an abacavir/lamivudine/dolutegravir regimen based on their weight. For many, this means taking dolutegravir in place of efavirenz or lopinavir/ritonavir in their current regimens. The shift in focus is based in part on inferences drawn from adult data generated by the NADIA and ARTIST studies that showed that lamivudine could be repurposed between first- and second-line treatment regimens.
Archery adds that this change is also supported by data from the ODYSSEY trial in which dolutegravir regimens outperformed traditional efavirenz or lopinavir/ritonavir combinations in children as young as two years old.
The Southern African HIV Clinicians Society is expected to meet with the South African National Department of Health to discuss potential changes.
“I thought I saw the end of malnutrition and HIV ten years ago”
Meanwhile, the department says it is already preparing to offer dolutegravir to even younger children under the age of six who are not currently eligible for treatment.
Health department experts recently approved the addition of pediatric dolutegravir for use in young children to the country’s list of essential medicines, national health department spokesman Foster Mohale said. Medicines must be on this list before they can be procured in large quantities for the country’s public sector or included in treatment guidelines.
Mohale says the country is currently updating its HIV treatment guidelines to allow broader access to pediatric dolutegravir for very young children in anticipation of the upcoming availability of dispersible formulations.
Currently, the preferred regimen for children approximately under six years of age is abacavir/lamivudine and lopinavir/ritonavir. If South Africa decides to allow younger children to take dolutegravir, these children will be able to substitute dolutegravir for lopinavir/ritonavir.
A move towards more effective and simpler pediatric HIV treatment comes as Archary, who works at a major hospital in the port city of Durban, sees growing numbers of children lost to sight and struggling with hunger. South Africa has been hit hard by COVID-19, which is believed to have killed an estimated 300,000 people, but has also led to widespread job losses and increased hunger. Much of the country around Durban also witnessed deadly flooding in April.
“We are seeing system disruption both from a societal perspective, but also in terms of health care delivery systems,” he says. “There is a lot of movement between [health] centers because of financial difficulties…we find a lot of patients who are lost to the system. »
Archary concludes: “I thought I saw the end of malnutrition and HIV ten years ago. Now it’s something we see much more often.”