PK and Safety Studies

Dolutegravir-based regimens are now recommended by the World Health Organization as alternative first-line antiretroviral regimens (ARVs) for people living with HIV, and several countries with high HIV prevalence have adopted the new regimens.

Short Regimen for Preventing TB Found Safe When Co-administered with New First-line HIV Drug 

IMPAACT4TB’s new study paves the way for scale-up of TB prevention among people living with HIV, who are dying from TB in large numbers.

This is an important moment for tuberculosis (TB) control, a new study finds that a shorter regimen to prevent TB can be safely co-administered with dolutegravir (DTG)—the first-line drug to treat HIV in many high-burden TB countries. Presented in March at the Conference on Retroviruses and Opportunistic Infections (CROI), the study found that 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. The findings put to rest fears of potential drug interactions with DTG and pave the way for scale-up of the 3HP regimen in 12 high-burden TB countries across three continents.                                                                                               

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 giving 3HP with DTG. Researchers enrolled 60 adults with HIV, who received DTG for eight weeks, then began 3HP; after completion of 3HP for 12 weeks, all participants were followed for four more weeks. Overall, co-administration of DTG and 3HP was well-tolerated.

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. Meeting in New York in September 2018, heads of states committed to providing preventive treatment to at least 30 million people, including six million people living with HIV by 2022.

Presentation: SAFETY & PK OF WEEKLY RIFAPENTINE/ISONIAZID (3HP) IN ADULTS WITH HIV ON DOLUTEGRAVIR by Kelly E Dooley, Johns Hopkins University, Baltimore, MD, USA

Next Steps

Based on results,  the IMPAACT4TB project is moving ahead with the introduction of 3HP in 12 high-burden countries: Brazil, Ghana, Ethiopia, Kenya, Tanzania, Malawi, Zimbabwe, Mozambique, South Africa, India, Cambodia and Indonesia. Together, these countries represent 50 percent 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.

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 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, an importation waiver to use rifapentine will be obtained through the Stop TB Partnership’s Global Drug Facility.

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 relevant treatment guidelines.

“We’re now preparing to start 400,000-600,000 people on 3HP across 12 countries in order to catalyze 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.”