The Central Drugs Standard Control Organization (CDSCO) has permitted the registration of the child-friendly formulation of the HIV drug lopinavir and ritonavir. The decision was taken on May 25 by an expert committee. The formulation of the HIV drug is considered child friendly, heat stable and is in the form of a pellet.
The decision comes as a relief to HIV infected children and their families, who were struggling to keep their children on antiretroviral therapy. Due to the shortage of child-friendly drugs, patients had to break adult tablets or consume the only other child-friendly alternative – a harsh tasting syrup formulation with 40% alcohol. In March, 637 children wrote to Prime Minister Narendra Modi, asking him to ensure that the lifesaving drug was made available. “We humbly request you to look into the matter of HIV drug stock out, in general, and in particular paediatric HIV medicines to ensure that they are not merely exported but also actually available to the children in this country,” they wrote. The Indian generic drug manufacturer Cipla, had recently ceased supply of the HIV drugs it supplied to National Aids Control Organization (NACO), due to large amounts of uncleared dues. Months of tussle had left patients suffering.
The Indian government’s decisions were taken in the thirty third meeting of the expert committee on antimicrobial and antiviral issues. In their recommendations, the committee noted that it had been extremely difficult to find patients and suitable institutions to conduct the feasibility studies for this formulation, from among India’s HIV positive paediatric population, prior to the approval of the product. The committee recommended the approval but has asked NACO to conduct a post-marketing surveillance with the first 100 patients and submit the data. Cipla has been asked to develop the questionnaire and protocol for this and submit it to CDSCO.
In 2013, the World Health Organization (WHO) recommended that lopinavir and ritonavir be administered to infants and children under three years. This is because the adult version has to be swallowed whole. The only other formulation accessible to children is a foul tasting syrup with 40% alcohol. Children are unwilling to take the drug in this form. These breaks in therapy develops their resistance to it, impeding their treatment.
“The lack of child-friendly HIV formulations is one of the major reasons why there is such a large treatment gap between adults and children, and is also why we consider paediatric HIV to be a ‘neglected disease,’” says Dr Suman Rijal, director of Drugs for Neglected Diseases Initiative (DNDI) in India.
“HIV infection progresses more quickly in children than adults. The younger the children are, the higher is the risk of dying of HIV. Globally, one in every ten HIV related deaths is of a child which can be easily prevented if the children are treated early. India is taking a step in the right direction by approving the use of lopinavir and ritonavir pellets for young children with HIV/AIDS,” says Dr Isaac Chikwanha, HIV medical advisor for MSF’s Access Campaign.
It is in response to this issue that the Indian generic drug manufacturer, Cipla, developed oral capsules for children, which can be sprinkled over food or dissolved in breast milk. Cipla’s drugs had been given a tentative approval by the US Food and Drug Administration in 2015, for introduction to some African countries. The pellet is produced in India and exported but has not been registered in India so far. Until May, it was also not available for procurement by Indian children. This, coupled with the non payment of dues to Cipla, had resulted in a country wide stock-out of the lifesaving drugs.
Paediatric HIV/AIDS is considered neglected as very few global manufacturers produce child-friendly dosages of the HIV medicines. DNDI and Cipla have been working on a ‘four-in-one’ fixed dose combination drug and are expected to put it up for development and registration to CDSCO soon. It could simplify treatment for infants and children, as it would be a fixed dose with lopinavir, ritonavir and other antiretrovirals like zidovudine, lamivudine and abacavir, lamivudine, which are recommended by the World Health Organization (WHO). “We now appeal to the CDSCO to prioritize registration of new child friendly fixed dose combinations of HIV medicines so that the national programme can reduce sickness and death among infants and young children with HIV/AIDS. With more children actually swallowing the medicines, there will be more survivors,” says Paul Lhungdim of the Delhi Network of Positive People.