Advanced medicines may remain elusive to India's HIV-infected children

Kids have been long neglected by pharma firms because their number is much less compared to adults suffering from HIV, and so there is little money to be made

Worried by the repeated shortage of medicines to control human immunodeficiency virus or HIV in infants, health activists and researchers are unclear about the availability of a 4-in-1 drug combination, which is an improvement over the existing HIV drugs for infants in India.
 
Even the National AIDS Control Organisation (NACO), a government body that manages India’s HIV and Acquired Immunodeficiency Syndrome or AIDS control programme, is concerned.
 
That is mainly because Cipla, a Mumbai-based multinational company, which makes HIV drugs for infants, has not been able to meet the drug demand of all infants in the past and it is not clear whether it can do so in the future.  

 

Infants find it hard to swallow the HIV tablets made for older children and adults, and require specific doses based on their age and weight.
 
But they have been long neglected by pharmaceutical companies because their number is much less compared to adults suffering from HIV, and so there is little money to be made.
 
In India, for example, just about 800 infants or children less than three years of age are registered to receive anti-HIV drugs. So, in 2013, Drugs for Neglected Diseases initiative — a Geneva-based non-profit organisation focused on drug development for neglected diseases (HIV in infants is considered as a neglected disease) — started working with Cipla to make the 4-in-1, which is a combination of four drugs — abacavir, lamivudine, lopinavir and ritonavir — that children need.

 
While the 4-in-1 drug was in the pipeline, Cipla introduced an interim two-drug (lopinavir and ritonavir) combination in the form of a syrup which works but has a bad taste. The 2-in-1 syrup has about 40 per cent alcohol, and requires refrigeration, which is a challenge in poor countries.
 
The other two drugs are administered separately. NACO started buying the syrup in 2012 to provide infants but next year it ran out of stock in some states. In 2015, Cipla stopped making the syrup, which led to more shortages in the following years. Some children reportedly died. Missing out doses also increases the chances of developing drug resistance. Cipla then told the media that the syrup was not a good product and NACO wasn’t paying it on time.

 
What it essentially wanted is for the government to switch to its 2-in-1 pellets — an improved version of the same syrup formulation — that has no taste, no alcohol, can be mixed in breast milk or food and doesn’t  require cold storage.
 
Activists say that Cipla discontinued the syrup without informing anyone. “This is how pharma companies, especially when they are the only suppliers, arm twist you into buying their products by creating a crisis,” says an official of NACO, who didn’t want to be quoted.
 
So, in 2017, NACO ordered some 2-in-1 pellet bottles to test whether it works for infants, and ordered lesser-known Haryana-based McNeil and Argus Pharmaceuticals to make the syrup.

 
Although NACO recently placed the orders to Cipla to supply 20,000 bottles of 2-in-1 pellets for the next two years, it remains unclear whether or not Cipla has the capacity to manufacture those many bottles that infants in India need.
 
Cipla refused to comment on this when Business Standard reached out. There have been stock outs of 2-in-1 pellets in African countries, including Kenya and Uganda, where Cipla was supplying the medicine. “The biggest concern is about such stock outs in India in future. We are trying to avoid them,” said a NACO official. Recently, Mylan, a Pennsylvania-based (US) pharma company also started making 2-in-1 and 4-in-1 pellets. But it, too, didn’t respond to queries from Business Standard about its registration and distribution plans.

 
Given this situation, the Drugs for Neglected Diseases initiative (DNDi), the NACO and humanitarian medical non-profit organisations such as Medicines Sans Frontiers are concerned about whether Cipla and Mylan will meet the demand for 4-in-1 pellets in the future.  “You can never be sure about that,” said Jessica Burry, HIV pharmacist with Medicines Sans Frontiers in Switzerland.
 
“Everyone is concerned,” added Jessica. 4-in-1 pellets have all the four drugs at one place. So, an infant won’t need to take many drugs and countries will need to order only one product instead of 2 or 3 for infants. 4-in-1 pellets are also said to be nine times smaller than 2-in-1 pellets, making them easier for infants to swallow.

 
“We want the pharma companies and the Indian government to make sure that 4-in-1 reaches all those who need it,” said Leena Menghaney, an HIV treatment activist in India. “We don’t want any more stock outs.”
Menghaney demands that Cipla should register the 4-in-1 in India and meet the demand of Indian infants first before supplying anywhere else. “DNDi is harnessing India's generic manufacturing capacity and so it should ensure that the drug is available here first,” she said.
 
Cipla refused to comment on its 4-in-1 manufacturing capacity, registration or distribution plan for India. But DNDi expects Cipla to register the combination with the US Food and Drug Administration (FDA) by this year-end. An official of DNDi said the organisation has been concerned about stock outs, and is internally discussing the need to work with more pharma companies to avoid stock outs in future. But nothing has been finalised as yet.

 
Pharmaceutical companies already make profits out of anti-HIV drugs for adults. So, they have the base materials required to make drugs for infants and can easily do so, says Burry.
 
“Besides, it is not just their money because DNDi and Unitaid (a global health initiative) have put considerable amounts of funds for working with pharma companies to develop drugs for children.
 
So, we have to hold these companies accountable,” Burry added.