A shorter regimen for preventing tuberculosis has been found safe when co-administered with a new first-line HIV drug.
Weekly administration of rifapentine and isoniazid (3HP) for three months in adults with HIV taking dolutegravir (DTG) was well-tolerated, with no need for dose adjustment.
DTG is a first-line drug used for HIV treatment in many countries with a high burden of tuberculosis.
The results presented at the Conference on Retroviruses and Opportunistic Infections, put to rest fears of potential drug interactions with DTG and pave way for scale-up of the 3HP regimen in high-burden TB countries.
“We’ve known for some time that preventive therapy for TB is a critical component of any effort to control the epidemic,” said Prof Gavin Churchyard, co-principal investigator on the study. “But current treatment options are too long and potentially more toxic.
“These findings will allow us move forward with co-administration of 3HP and DTG, offering the best treatment options to those who need it most.”
“We’re now preparing to start 400,000 to 600,000 people across 12 countries on 3HP to catalyse an increase in supply, demand for and uptake of 3HP,” added Prof Churchyard. “The next few years will focus on reducing the price of 3HP and addressing barriers to supply at the global level.”
The 12 high-burden countries, which represent 50 per cent of the global burden are Brazil, Ghana, Ethiopia, Kenya, Tanzania, Malawi, Zimbabwe, Mozambique, South Africa, India, Cambodia and Indonesia. “The project will prioritize 3HP for people living with HIV and children under five, and subsequently all those in close contact with TB patients,” Prof Churchyard said.
“In high-TB burden countries where rifapentine is not yet registered, an importation waiver to use rifapentine will be obtained through the Stop TB Partnership’s Global Drug Facility,” he added.
In Kenya, adolescents and adult men are on the first-line ARV drug DTG, but pregnant women are not put on it, due to concerns about birth defects.
The study, funded by Unitaid 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 of administering 3HP with DTG.
60 ADULTS ENROLLED
Researchers enrolled 60 adults with HIV, who received DTG for eight weeks, then began 3HP. After completion of the 3HP regimen, all participants were followed for four more weeks. Overall, co-administration of DTG and 3HP was well-tolerated. “We now know that it’s safe to take these two game-changing regimens together, and it also appears that doses of dolutegravir do not need to be adjusted,” said Dr Kelly Dooley, associate professor of medicine at the Johns Hopkins University School of Medicine and co-principal investigator on the study.
“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,” he said.
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. Preventive therapy, including 3HP, is one of the best ways to keep individuals and families safe from TB, which in turn helps communities become and remain TB-free. Large, multi-country clinical trials have established the efficacy of 3HP in preventing TB. In February 2018, the World Health Organisation released consolidated guidelines for the treatment of latent TB infection that recommend the use of 3HP for people living with HIV and contacts of tuberculosis cases of any age.
“The 3HP regimen gives us hope that by using a find, treat and prevent TB strategy, we will finally end the TB epidemic.”
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.
“People being successfully treated for HIV are now dying from TB in high numbers, and that’s unacceptable,” said Dr Yogan Pillay, deputy director general of health at the South African National Department of Health. “These new findings will prevent many of these deaths.”
3HP is already approved for the treatment of TB infection by the US Food and Drug Administration and is recommended by the US Centers for Disease Control and Prevention. The results of this study will be shared with the WHO and project countries and the Aurum Institute will work closely with them so that the findings can be included in treatment guidelines.