NEW DELHI :
A shorter treatment for tuberculosis (TB) can be safely co-administered with dolutegravir (DTG), the first-line drug to treat HIV in many high-burden TB countries, a new study has found.
The regimen will soon be introduced in 12 high TB burden countries, including India.
Weekly administration of rifapentine and isoniazid (3HP) for three months in adults with HIV taking DTG was well-tolerated, with no need for dose-adjustment, scientists found. The findings put to rest fears of potential drug interactions with DTG and pave the way for scaling up the 3HP regimen in high-burden TB countries.
The study, funded by Unitaid, a global health initiative working on TB and HIV, and carried out in South Africa by the Aurum Institute and the Johns Hopkins University Center for TB Research, looked at the safety and pharmacokinetics (the movement of drugs within the body) of giving 3HP with DTG. Aurum, through the Unitaid-funded IMPAACT4TB project, is moving ahead with the introduction of 3HP in 12 high-burden countries. These countries—Brazil, Ghana, Ethiopia, Kenya, Tanzania, Malawi, Zimbabwe, Mozambique, South Africa, India, Cambodia, and Indonesia—represent 50% of the global TB burden. The project will prioritize 3HP for people living with HIV and children under five, and subsequently all those in close contact with TB patients.
The 3HP regimen is already approved for the treatment of TB infection by the US Food and Drug Administration (FDA) and is recommended by the US Centers for Disease Control and Prevention. The Aurum Institute and its partners will also be pursuing regulatory approval of 3HP products in project countries. In high-TB burden countries where rifapentine is not yet registered, importation waiver to use rifapentine will be obtained through the Stop TB Partnership’s Global Drug Facility.
“We’ve known for some time that preventive therapy for TB is a critical component of any effort to control the TB epidemic. However, current treatment options are too long and potentially more toxic. These findings will allow us to move forward with co-administration of 3HP and DTG, offering the best treatment options to those who need it the most," said Gavin Churchyard, group chief executive officer of the Aurum Institute and co-principal investigator on the study.
Researchers enrolled 60 adults with HIV, who received DTG for eight weeks, then began 3HP. After completion of 3HP, they were followed for four more weeks. Overall, co-administration of DTG and 3HP was well-tolerated.
“These are the results we have all been waiting for. The evidence that 3HP is safe to use with dolutegravir, today’s most advanced HIV treatment, allows us to scale up short-course preventive therapy for TB, which is the leading cause of death in people living with HIV," said Unitaid executive director Lelio Marmora.
People living with HIV are at high risk of developing TB and are 20 to 37 times more likely to move from latent infection to active TB. The 3HP regimen offers a shorter, safer alternative to the older standard of care—isoniazid preventive therapy (IPT)—in which people take isoniazid every day for between six and 36 months. Large, multi-country clinical trials have established the efficacy of 3HP in preventing TB.
The estimated cases of TB in India was approximately 2.8 million, comprising about a quarter of the world’s TB cases, according to the Global TB Report 2017.