Experts call for registration of new ARV formulation suitable for children

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Children living with HIV need to take several different antiretroviral (ARV) pills or syrups twice a day, while most adults in South Africa have been offered a pill once a day for about a decade.

At the recent South African HIV Clinicians Society (SAHCS) conference, various speakers argued that better treatment regimens for children are urgently needed.

According to Professor Moherndran Archary, who represents the interests of children and adolescents at SAHCS, there are several possibilities to improve access to simplified treatment for children.

One of those opportunities is simply to make available new child-friendly formulations of existing drugs. “The use of dispersible tablets in children will allow for simplified once-daily treatment regimens that can be dissolved in liquid and swallowed, chewed or swallowed whole – allowing flexibility of administration for caregivers,” he said. he told Spotlight.

He says that in the longer term, they are eagerly awaiting several studies that evaluate long-acting formulations in children, which will allow patients to receive an injection that would last two months or more. Such injections have already had impressive results in trials conducted in adults.

Need to register child-friendly dolutegravir

Archary says an urgent step towards simplified treatment options for children in the country is for the South African Health Products Regulatory Authority (Sahpra) to register a dispersible 10 mg tablet of dolutegravir.

In recent years, dolutegravir has become the backbone of HIV treatment in adults due to its high efficacy in suppressing HIV and its excellent side effect profile.

Besides the advantages of such a formulation being dispersible – current pills are pills you have to swallow – the 10 mg dosage will also allow for more accurate dosing in children.

Dr Leon Levin, chief pediatric technical specialist at Right to Care (an NGO) agrees that it is “absolutely essential” that the dispersible dolutegravir 10 mg tablet be registered by Sahpra as soon as possible.

He points out that several other African countries like Eswatini, Zimbabwe and Zambia already have access, while South Africa, which has the world’s largest ARV program, lags behind. “This formulation will literally revolutionize the treatment of these young children. Only Sahpra stands in the way, ”he said.

According to Department of Health spokesperson Foster Mohale, dolutegravir is currently only available in South Africa for children and adolescents as a single 50 mg tablet and a combined dose pill. fixed tenofovir, lamivudine and dolutegravir (containing 50 mg dolutegravir).

Research on the
SahpraThe website shows that the products dolutegravir 10 mg and dolutegravir 25 mg were registered in November 2020. But, according to Archary, these are not dispersible formulations and can only be used in children weighing more than 20 kg.

Sahpra spokesperson Yuven Gounden confirmed that the currently registered dolutegravir 10 mg product is a pill that must be swallowed with water. He said it is only indicated for children aged six and over.

Gounden said Sahpra has received applications to register dolutegravir 10 mg dispersible products and that these applications have been prioritized.

Mohale says the department plans to start using the dolutegravir 10 mg dispersible tablet once it is registered by Sahpra. “This formulation is dispersible, scored and strawberry flavored, allowing the youngest children living with HIV between 3 and 20 kg to be treated with the best drugs available,” he says.

New combinations

While the immediate call is for Sahpra to approve the dispersible 10 mg dolutegravir tablet, Archary says that in the future, a fixed-dose combination of abacavir, lamivudine and dolutegravir will further simplify treatment in children. For now, however, things are a little more complicated.

Mohale points out that South Africa recently introduced a fixed-dose combination of abacavir and lamivudine suitable for children and adolescents. For now, it is combined with lopinavir / ritonavir (LPV / r), but the hope is to combine it with dispersible dolutegravir once it becomes available.

LPV / r is mostly taken in pill or syrup form, but the government also buys it in granule form. “This formulation offers an alternative option for infants and children [older than] 6 months old who cannot tolerate LPV / r syrup (which may be unpleasant to the taste) and cannot swallow LPV / r tablets whole. With its better taste, it aims to improve palatability and adherence to treatment to improve viral suppression, ”says Mohale.

“To date, all provinces have purchased the product, and nurses and doctors can prescribe LPV / r oral granules,” he says.

While the LPV / r lozenges and fixed dose combination abacavir / lamivudine are an improvement over previous options, a superior formulation of these same drugs is underway.

In 2020, the pharmaceutical company Cipla, in partnership with the NGO Drugs for Neglected Diseases, announced that it had developed a fixed-dose combination of abacavir, lamivudine and LPV / r for infants and young children under three. years. The product consists of capsules containing strawberry flavored granules (the size of granulated sugar) which can be taken with food or milk.

The product was reportedly submitted to Sahpra for registration in 2020, but based on a search we performed on Sahpra’s website, it does not appear to have been registered yet.

“[For] the government, and the world, to come up with this innovative way of doing treatment for children living with HIV / AIDS, is because when children are zero to one year old, two years old, three years old, it doesn’t ‘there’s no way they can swallow a pill, and when you crush it it gets more bitter,’ says Portia Serote, a health activist from Daveyton in the East Rand.

“Second, it was a question of measure for those who took a syrup [and] sometimes parents are not very educated and informed, ”she says.

“Sometimes when they’re supposed to give like 0.5 mg of syrup you find that they give too much or not enough which was a problem because if you don’t give enough it might not work as in which it is supposed to work and if you give too much again it could be a problem as the side effects become more severe than expected.

Second line and drug resistance

According to Mohale, children who fail their first-line antiretroviral regimen may be placed on a second-line regimen, which is described in the South African HIV treatment guidelines, depending on their first regimen.

“In the event of second-line failure, or failure of a protease inhibitor (such as lopinavir / ritonavir), these cases can be referred to the third-line antiretroviral treatment committee for a treatment regimen recommendation on a case-by-case basis. case, ”he said. Explain.

Archary says it is important to ensure that we limit transmitted drug resistance and HIV transmission by keeping an adult HIV population suppressed.

“Drug resistance in children is a product of difficulties in administering unappetizing treatment regimens and drug interactions (especially with treatment for tuberculosis) – resulting in suboptimal drug levels in children”, he said.

* This article was produced by Projector

– public interest health journalism.


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