An easy-to-consume, heat-stable, fixed-dose combination of four antiretrovirals (ARVs) developed for HIV-infected infants and young children weighing 3 to 25 kg is currently under review by the US Food and Drug Administration (FDA).
If approved by the FDA, this all-in-one regimen, consisting of the four antiretroviral medicines lopinavir, ritonavir, abacavir and lamivudine, could prove to be a game-changer for millions of HIV-infected infants and children around the world, especially in low- and middle-income countries.
Not only is it a very child-friendly formulation (as opposed to the currently available regimens), this new fixed dose combination, called Quadrimune, comes at an affordable price. The Indian pharmaceutical company Cipla, which developed the drug in partnership with the Drugs for Neglected Diseases Initiative and Unitaid, has committed to price the product at less than one US$1 a day to make it affordable.
Of the estimated 1.7 million children under age 14 living with HIV globally, almost 90 percent live in Sub-Saharan Africa. Of these, 1.1 million are aged 0-9 years, 160,000 of them newly infected with HIV in 2018. Only an estimated 54 percent of children living with HIV have access to treatment. More than 300 children die from the disease every day. Inappropriate and suboptimal treatment options contribute to low treatment coverage.
Children born with HIV become infected through their HIV positive mothers and through no fault of their own. Children form a vulnerable group, yet they remain a neglected lot insofar as development of optimal child-friendly antiretroviral formulations for infants and children are concerned.
“While a lot of progress has been made to simplify treatment regimens for adults living with HIV, unfortunately no one has bothered about children, as they form a very small group of patients and so do not represent a lucrative market for the pharmaceutical industry”, said Dr. Francois Bompart, Director of Pediatric HIV and Hepatitis C virus, at the neglected diseases initiative, in an interview given to Citizen News[JB1] Service, official media partner of the 20th International Conference on AIDS and sexually transmitted infections in Africa (ICASA 2019), held in Kigali, Rwanda.
For children in many parts of Africa, the recommended treatment for years has consisted of a very unpalatable and long lasting bitter-tasting syrup, with 40 percent alcohol content, that uses two of the ARV drugs, which is administered along with two other drugs. The syrup has to be refrigerated and it is very bulky. Transporting a heavy load of the syrup bottles from far-off hospitals to their homes becomes a challenge for mothers of children with HIV. Moreover, in the absence of refrigerating facilities, often the mothers bury the bottles in sand to keep them cool.
Another challenge is that as the bottles are visible, disposal becomes a problem as the neighbors can see the bottles and come to know that there is a child with HIV in the family, which stigmatizes them as well. All these hurdles result in a strong chance that treatment will be disrupted and/or totally opted out of, Bompart added.
But now finally there is a treatment designed specifically for infants and young children, who are at a high risk of dying if they are not treated. The new formulation doesn’t require refrigeration and is easy to administer to infants and children of different weights and ages. It comes in the form of a very fine tasteless powder kept inside a tiny capsule which the mothers can open, then mix the powder with food or milk so that the baby does not even realize what he or she is eating.
While the price of the current regimen – the syrup plus the two standalone drugs – being given to children is US$20 per month, Cipla will provide Quadrimune for US$15 per packet of 120 capsules, or US$1 per day for children weighing 10 to 13.9 kg, and at 50 US cents per day for younger children and infants.
“It is also critically important to not just treat the babies, but to also ensure that HIV infected pregnant women are properly treated to prevent transmission of the virus from mother to child,” Bompart said. “While we have to work for less and less children to be infected with HIV, we also need to take better care of those already infected. If kids are not treated, half will die before the age of 2 years. But those who survive need to be protected from the damage the virus does to their body. And this is what this adapted formulation aims for.”
Meanwhile, DNDi has begun a study in Uganda to look at the efficacy, safety and acceptability of this formulation in HIV-infected children. The first round of results obtained in 16 children are extremely encouraging, both from the side of the pharmacokinetics of the drug as well as its acceptability by mothers and children. Two other studies are also underway to examine some additional benefits of the new medication. A study by South Africa's Stellenbosch University is trying to find out if this product can be used in neonates and if it can also stop the virus in its tracks to prevent infection in those kids who are exposed to the virus from their mothers but are not infected.
Yet another South African study will examine if any dose adjustment of the drug is needed for those children with HIV who are co-infected with TB.
Once approved by the FDA and validated by the WHO, this optimal child-adapted all-in-one ARV regimen holds the promise of being a game-changer in addressing the treatment needs of millions of infants and young children infected with HIV.
Shobha Shukla is the founder and Managing Editor and Executive Director of Citizen News Service. Follow her on Twitter @Shobha1Shukla, @CNS_health, or visit www.citizen-news.org