New Delhi: Last March, India’s AIDS control programme ran out of a key drug for children living with HIV. The stock-out of Lopinavir and Ritonavir syrup meant that caregivers were physically breaking tablets meant for adults into fragments for children. This, of course, runs the risk of either over-dosing or under-dosing.
As reports about the stock-out began to trickle in, the parliament session was still ongoing. For a change, parliamentarians actually took up the issue and submitted formal questions to the Union health ministry.
The HIV community was in distress – 637 children signed a letter to the prime minister. “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 stock out was due to bureaucratic failings – India had reportedly not paid upwards of Rs 6 crore in dues to Cipla, who was the sole manufacturer of this syrup. Cipla finally stopped supply.
The months of confusion affected around 651 children who could have been in need of the drug (the pellets are meant for children between three months to three years. Other factors such as weight are also considered to determine eligibility).
Now more than a year later, India’s AIDS control programme is still figuring out how best to serve children living with HIV with this drug.
‘Neglected disease’
Some organisations call paediatric HIV a ‘neglected disease’ due to how little attention it receives from pharmaceutical companies and in public policy (children account for about 5% of those on anti-retroviral therapy).
The anti-retroviral regimen for people with HIV is complex, decided on a number of factors such as their CD4 count, age and weight. This will determine the dosage, frequency and type of formulation they have to take.
For children with HIV, one of the drugs administered to them in India has been a syrup formulation of Lopinavir and Ritonavir (LPV/r), which Cipla used to make. India’s AIDS control programme has been and is still giving this syrup to children, now sourced from a lesser known Indian company (McNeil & Argus Pharmaceuticals). The pellets are intended as a first-line treatment for HIV and is given along with other drugs.
But this oral syrup has its downsides – it is not heat stable, which makes its cold-transport and storage difficult (it needs to be kept between 2 and 8 degrees Celsius), it requires to be kept cool at home too which is not easy in Indian homes (in Kenya for example, some caregivers reportedly would store the bottles in wet mud to keep it cool), the syrup is bitter tasting for children and it has over 40% alcohol content.
The second option of breaking adult tablets into smaller is inconvenient and also imprecise (during the stock-out, NACO had issued a notice to anti-retroviral centres, telling them to explain to parents how to break tablets).
There is a third option – the same combination also comes in the form of pellets. These pellets can be twisted open and sprinkled over food or dissolved in breast milk. These pellets do not need refrigeration, don’t contain alcohol and have masked the potent taste of the syrup considerably. While more expensive than the syrup, pellets save money on storage, shipment and wastage.
Last May, after three months of the crisis over the LPV/r syrup, the Indian drug controller’s subject expert committee gave the green light for this pellet formulation. The condition for this was that the National AIDS Control Organization (NACO) would conduct a post-marketing surveillance in the first 100 patients and submit this data. Cipla was itself told to develop the questionnaire and protocol for the surveillance. Prior to this approval, both the drug controller general of India and the NACO had expressed interest in the pellet formulation.
More than a year later, the Indian government continues to dispense the syrup formulation and has not scaled up the distribution of pellets. Details about the post-marketing surveillance are also not publicly made available by the government.
Pellets only in a pilot-programme
“India’s AIDS programme is not giving fridges to mothers. But they’re giving mothers this syrup for their children, which needs to be kept in the fridge,” says Leena Menghaney at Medecins Sans Frontieres.
India has decided to take a slow approach on the roll-out of the pellets. The drug is only being given in a limited manner, in about ten government run ‘centres of excellence’ around the country. Anyone who wants the pellet, will have to collect it only from these centres, if there is one in their state.
This slowness is not coming from a concern about the safety of the LPV/r pellets: “Same thing is being given in the syrup and tablet already, so we are not doubtful of the safety in the pellet. But we want to see other factors,” says R.S. Gupta, the deputy director general at NACO.
The pilot programme is thus examining factors such as “feasibility, drug compliance, consumer convenience, adherence and mother’s satisfaction.”
There are about 400 children around India who are currently receiving pellets in this programme, he says. All three formulations are currently on the WHO’s list of essential medicines.
One paediatrician running the pilot at one of the ten centres of excellence, was not moved by the crisis of stock outs, the confusion over formulation and the bureaucratic lapses that trigger this: “People shouldn’t whine. They are getting all these drugs for free. India is a large country. People should be more grateful.” On the issue of caregivers breaking up tablets during stock outs the doctor said, “There is no problem here.”
But the doctor said all of this while also saying that the government had “no safety concern with the pellets. This is a known and approved drug used in many countries,” that “there is a definite advantage of pellets over syrups in terms of heat stability. Wrong temperature during transportation is a big risk,” and that as doctors they were “not comfortable that this syrup was coming from a local company. It is not as well known as Cipla.”
This kind of attitude from the government worries long time HIV-AIDS activists. “No one can break these tablets precisely at home. ART centres are supposed to give people the best medicines. How can they themselves be suggesting that people take wrong dosages? Busy working mothers from poor sections of society will not find it easy to do all this,” says Paul Lhungdim at the Delhi Network of Positive People (DNP+).
“We know this syrup is coming from Haryana and we are not confident of its quality,” says Lhungdim. “NACO should quickly finish this study and start making these pellets available across India.”
“India should consider using the pellets more widely. It is the same drug, it is just in a different form. Previously when the syrup was being used, there were no other options. Abbott had control over this market as no one was keen to invest in further research and neither was Abbott. Now that this pellet is available, it should be scaled up,” says Menghaney.
Despite being nearly a year and a half since the confusion over the various formulations and the exposing of the government’s negligence in paying Cipla, India is still sorting out how it handles its paediatric HIV patients. “NACO’s pilot programme is still working on this… It may finish in another few months,” says Gupta.