WASHINGTON, DC — Last year, 330,000 infants were born infected with HIV, many of whom will succumb to the disease unless more baby-friendly formulations of antiretrovirals become available, AIDS advocates warned here yesterday at the International AIDS Society conference. “We know that existing treatments are very often difficult to administer,” Bernard Pécoul, executive director of the Drugs for Neglected Diseases initiative (DNDi), a Geneva-based non-profit that works to foster new treatments, told meeting attendees.
Newborns cannot swallow large pills, for example, and caregivers cannot crush tablets because this destroys their efficacy. Syrup-based formulations can be easier to administer, but bottles of these liquid drugs can be difficult to transport given their weight—a real issue in rural regions where this is done on foot—and families struggle with refrigerating and measuring the syrup, according to Adeodata Kekitiinwa-Rukyalekere, a pediatrician at Mulago National Hospital in Kampala, Uganda. What’s more, the suspension also contains alcohol, making the bitter taste of the medicine even more unpalatable than it already is.
In an effort to develop an effective and baby-proof option, last week DNDi announced a partnership with the Indian drug giant Cipla to develop the first four-in-one HIV drug combination in sprinkle form to address the unmet need of medicines for the very young. The sprinkles, which they aim to ultimately package in small, easy-to-transport packets, will contain the protease inhibitors lopinavir and ritonavir as well as the therapeutic agents abacavir and lamivudine.
In January, Gilead Sciences of Foster City, California, received approval from the US Food and Drug Administration for an oral powder version of the antiretroviral tenofivir (sold under the brand name Viread) for youngsters ages two to five. But “tenofivir is not indicated for very young children, and it’s just one drug” as opposed to a combination, says Jaideep Gogtay, head of the Medical Services division at Cipla, which is headquartered in Mumbai. Cipla already has a sprinkle version of lopinavir and ritonavir (which are sold together in high-income countries under the brand name Kaletra by Chicago’s Abbott Laboratories), and recent results from the CHAPAS-2 trial comparing these sprinkes against a syrup version revealed that 71% of families of children under the age of 1 in the trial chose to continue the sprinkles over the syrup after the study concluded.
The challenge now will be to create a granulized version that also contains abacavir and lamivudine (drugs currently marketed together by the UK’s GlaxoSmithKline as Epzicom or Kivexa) to enable the infants to receive all of the drugs in sprinkles, which could be given orally or mixed with food. Researchers in Cipla’s Mumbai labs will work to find a way to create granules that are coated to protect the drugs from the stomach’s acid environment, which can degrade the active ingredients.
If the creation of the four-in-one sprinkles goes according to plan, the partnership aims to begin clinical trials in 2015, according to Shing Chang, scientific advisor to DNDi.