For people starting HIV treatment, combining dolutegravir-containing antiretroviral therapy with 3HP TB preventive treatment is safe and works effectively in tandem.
DENVER (March 5, 2023) — New clinical trial results show that the best-in-class treatment for HIV works well with one of the best tuberculosis (TB) preventive treatments. The trial looked at people who had yet to start treatment for HIV, evaluating how dolutegravir (DTG)-based antiretroviral therapy (ART) works when taken together with 3HP, a short, three-month course of isoniazid and rifapentine. The results, showing the safety of starting DTG-based ART and 3HP TB preventive treatment at the same time, were presented today at the 2024 Conference on Retroviruses and Opportunistic Infections (CROI) in Denver, Colorado.
Each year, there are an estimated 670,000 new TB cases among people living with HIV and an estimated 167,000 deaths from TB-related HIV. The findings of the study, funded by Unitaid through the IMPAACT4TB project, show the promise of simultaneous initiation of DTG and 3HP to prevent a major health threat in sub-Saharan Africa and the world.
“An ounce of prevention is worth a pound of cure and, whenever possible, it is best to get that ounce in early,” said Ethel Weld, MD PhD, an assistant professor of medicine at the Johns Hopkins University School of Medicine and the principal investigator in the study. “This study looked at the safety, efficacy, and drug levels of DTG when given together with 3HP from the outset in new HIV patients. Though an expected interaction was seen, DTG still held down HIV viral loads, and the combination was safe and well-tolerated.”
The trial—called “DOLPHIN-TOO”—focused on DTG drug concentrations in blood among people living with HIV who had never previously been treated with ART and who are also taking 3HP or 6 months of isoniazid (6H). At the same time that the patients started DTG, they also started either 3HP or 6H. Studies have shown the 3HP regimen is preferred by patients, has less toxicity, and is more achievable for patients to complete than the longer courses of isoniazid (which can last up to a year in some places).
The trial focused on whether the levels of DTG in the blood were impacted by the 3HP regimen. The results showed that, while people in the 3HP group did have lower levels the DTG in their blood stream than people in the 6H group, they were nonetheless able to achieve viral suppression (an undetectable level of HIV virus in blood) by 8 weeks and maintain it for the length of the six-month study. Minimal side effects were seen, none were severe, and the majority were resolved with continuation of therapy. Previous research released at the Union World Conference on Lung Health in November of 2023, had provided information on the safety and efficacy of the use of 3HP and DTG together, without data on the drug levels in the blood.
This study points to the use of short course TB preventive treatment in people who are newly diagnosed with HIV and are at highest risk of active TB disease. The results will inform WHO and country level policy on the timing of TB preventive treatment in people who are newly initiating DTG based ART in high burden TB countries globally. This study complements previous studies conducted by the Unitaid-funded IMPAACT4TB consortium that determined the safety of use of 3HP in people living with HIV who are already established and virally suppressed on DTG-based ART. Those studies increased the demand for the product, which led to a reduction in the price of the product, fostering widescale access to short course TPT. This is expected to reduce TB mortality by 150,000 by 2035.
“For patients with HIV, the best time to start TB preventive treatment is when they are first starting ART,” said Professor Gavin Churchyard, the group CEO of the Aurum Institute. “This is when patients are most closely monitored and are in regular contact with clinics and healthcare providers, making it easier to monitor them for any potential side effects. Seeing how safe and effective simultaneous initiation of 3HP and DTG-based ART is, this approach needs to be adopted in every country where TB is prevalent. The only way we will end TB is if we systematically prevent new TB cases in people with HIV up front—and we now have the recipe to do so.”
“This research gives programs the green light to fully integrate 3HP into the care of people with HIV right from the very beginning of HIV treatment,” said Mike Frick, co-director of the TB program the Treatment Action Group, a community-based research and policy think tank. “We already knew that it was okay to use 3HP and dolutegravir together in people experienced with HIV treatment. Now we know the same is true for people who are just starting HIV treatment for the first time. National governments should feel confident using 3HP in HIV programs, and donors, including the President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund, should support countries in procuring 3HP as an essential part of the HIV clinical care package."
Note to editors:
About IMPAACT4TB
The Increasing Market and Public Health Outcomes Through Scaling Up Affordable Access Models of Short Course Preventive Therapy for TB (IMPAACT4TB) Consortium is led by the Aurum Institute and comprised of Unitaid, the Clinton Health Access Initiative (CHAI), Johns Hopkins University, KNCV the Dutch TB Foundation and the Treatment Action Group (TAG).
People living with HIV (PLHIV) and child contacts are at highest risk of contracting TB. The initial IMPAACT4TB grant looked at the safety of co-administering and dosing of 3HP and DTG and, once that was ascertained, the project moved on to introduce and roll out 3HP as an additional TPT option among PLHIV and household contacts of TB patients in 12 low-middle income countries, namely: Brazil, Ethiopia, Cambodia, Indonesia, South Africa, India, Zimbabwe, Kenya, Malawi, Mozambique, Ghana and Tanzania.
Although the project was focused in these 12 countries, efforts were also made to ensure wider access to 3HP. These efforts saw over 70 additional countries procuring 3HP for use among eligible populations. The grant also funded studies on the use of 3HP in ART-naive patients on DTG-based regimens (DOLPHIN TOO), dosing of 3HP in children from 0-2 years (TBTC Study 35) and improved TPT service delivery, as well as community advocacy for improved TPT policy and uptake within project countries. www.impaact4tb.org
About Unitaid
Unitaid saves lives by making new health products available and affordable for people in low- and middle-income countries. Unitaid works with partners to identify innovative treatments, tests and tools; helps tackle the market barriers that are holding them back; and gets them to the people who need them most—fast. Since it was created in 2006, Unitaid has unlocked access to more than 100 groundbreaking health products to help address the world’s greatest health challenges, including HIV, TB and malaria; women’s and children’s health; and pandemic prevention, preparedness and response. Every year, these products benefit more than 170 million people. Unitaid is a hosted partnership of the World Health Organization. https://unitaid.org/#en
About Aurum Institute
The Aurum Institute is a proudly African organisation working to advance health, science and innovation to create a healthier world for future generations. We partner with governments, the private sector and civil society to design and deliver high-quality care and treatment to people in developing communities. https://www.auruminstitute.org/
Source: IMPAACT4TB