Child-Friendly Formulation of WHO-Recommended HIV Treatment Now Approved by the CDSCO

June 6, 2017 India

6 June 2017, New Delhi: On 25 May, an expert committee of the Central Drugs Standard Control Organization (CDSCO), the Indian drug regulatory authority, finally permitted the child-friendly and heat-stable pellet formulation of the HIV drug lopinavir/ritonavir (LPV/r) to be registered. This has opened up crucial supplies from Cipla to the Indian National AIDS Control Programme (NACO), which had up to now been struggling to source quality assured paediatric formulations of the drug.

Quote from Delhi Network of Positive People (DNP+):

New innovations like these make it easy for families to administer the lifesaving treatment, yet infants living with HIV in India are the last to receive access to the LPV/r pellet due to regulatory delays. We now appeal to the CDSCO to prioritise 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. These innovations represent very important progress in the fight to end AIDS in children.”

– Paul Lhungdim of the Delhi Network of Positive People (DNP+)

Quote from Doctors Without Borders/Médecins Sans Frontières (MSF):

“HIV infection progresses more quickly in children. The younger the children are, the higher is the risk of dying of HIV. Globally, one in every ten HIV-related death is of a child which can be easily prevented if the children are started early on treatment. India is taking a step in the right direction by approving the use of LPV/r pellets for young children with HIV/AIDS. We now hope that more new antiretroviral drug combinations for children will be registered in India in the future so they can have more options.”

– Dr Isaac Chikwanha, HIV medical advisor for MSF’s Access Campaign.

Quote from the Drugs for Neglected Diseases initiative (DNDi):

“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.’ The registration of the pellets is a positive sign as the needs of children are being addressed. Luckily, even better medicines will soon be available, including ‘4-in-1’ fixed-dose combinations that DNDi is developing with Cipla Ltd. We hope this key tool will also be considered for prioritisation for development and registration. Children are some of the most vulnerable HIV patients, and we cannot forget their special R&D needs.”

– Dr Suman Rijal, Head, DNDi India.

Background

Pediatric HIV/AIDS is a neglected disease and few manufacturers globally come forward to produce child doses of HIV medicines. However, Indian generic manufacturers have consistently invested in making better HIV medicines for children.

Since 2013, the WHO has recommended lopinavir/ritonavir (LPV/r), an HIV protease inhibitor, as an essential component in the first-line treatment for infants and children less than three years old. The drug’s adult version has to be swallowed whole and thus cannot be given to infants and young children. LPV/r’s sole paediatric formulation is a foul-tasting syrup that not only contains 40% alcohol but also requires cold-chain transport. Caregivers struggle to get infants and young children to take the syrup as it tastes bad, and they are likely to spit it out or refuse it altogether. When kids do not get the proper dosage of their ARVs, they can develop resistance to the drug, which has serious consequences for their health and future ARV treatment options.

In response to this problem, oral pellets of LPV/r have been developed by the Indian generic company Cipla. The pellets, which come in capsules and are dosed by weight, can be sprinkled (but not stirred or crushed) over a small amount of soft food. For infants—who must be able to swallow them—the pellets can be added to a spoonful of breast milk or put onto the infant’s tongue. However, infants and children still need two other HIV drugs for effective treatment.

In May 2015, the US Food and Drug Administration granted tentative approval to the pellets developed by Cipla and some countries in Africa introduced the new formulation so that young children with HIV could benefit immediately. Yet the pellet formulation – which is produced domestically and exported – had not been registered in India itself, and until last month was not available for procurement for Indian children that desperately needed a better formulation of LPV/r. Meanwhile, the older syrup formulation had already been phased out of production by Cipla in 2016. Last week’s approval of the pellet formulation by the CDSCO is also an important step to address the situation of imminent shortages of the paediatric drug in the country.

As part of its programme to develop improved HIV medicines for children, the Drugs for Neglected Diseases initiative (DNDi) is working with Cipla to ensure the new pellets are registered and available to HIV treatment programmes in developing countries. In September 2015, DNDi launched the LIVING study in Kenya to demonstrate the effectiveness and safety of LPV/r oral pellets to help enable early access to this new LPV/r formulation. The study is now being expanded to other countries in Africa.

DNDi and Indian generic companies are also collaborating in the R&D for an innovative 4-in-1 fixed dose combination of HIV medicines that will greatly simplify treatment for infants and children. The next step is to develop two “4-in-1” fixed-dose combinations of LPV/r with other key ARVs (zidovudine/lamivudine and abacavir/lamivudine) that are recommended by the World Health Organization (WHO). Taste-masked versions of these combinations will be even easier to take and will greatly simplify treatment for infants and children.