1-month treatment as effective as 9-month treatment for preventing TB in HIV

by NIH media contact: Hillary Hoffman
March 05, 2018

Image with caption: Dr. Susan Swindells

Dr. Susan Swindells

A one-month antibiotic regimen to prevent active tuberculosis (TB) disease was at least as safe and effective as the standard nine-month therapy for people living with HIV, according to results of a large international clinical trial.

Adults and adolescents in the trial were more likely to complete the short-course regimen consisting of daily doses of the antibiotics rifapentine and isoniazid for four weeks than the standard nine-month regimen of daily isoniazid.

The Phase 3 clinical trial, called ACTG 5279, was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, and conducted by the NIAID-funded AIDS Clinical Trials Group (ACTG).

Susan Swindells, M.B.B.S., University of Nebraska Medical Center Department of Internal Medicine professor and medical director of the HIV Clinic, is lead author of the study.

"I have spent my whole career trying to help people, and it has been incredibly rewarding," Dr. Swindells said. "With this trial though, we may be able to help literally millions of people. Our results will change treatment guidelines on a global scale, and we hope it will make it much easier for many more people to get treatment for TB infection. Our findings will benefit people in Nebraska and around the world."

Richard E. Chaisson, M.D., professor of medicine, epidemiology and international health at Johns Hopkins University and co-chair of the trial, presented the findings March 5 at the 2018 Conference on Retroviruses and Opportunistic Infections in Boston. Dr. Swindells and UNMC colleagues Courtney Fletcher, Pharm.D., and Anthony Podany, Pharm.D., also will be at the conference.

"Globally, tuberculosis kills more people than any other infectious disease, and it is the leading cause of death for people living with HIV," said NIAID Director Anthony S. Fauci, M.D. "These results have the potential to dramatically change clinical practice by offering people living with HIV who are at risk of developing active tuberculosis an additional, shorter-duration prevention option that is safe, effective and more convenient. This study also will inform future research on prevention of tuberculosis disease among HIV-negative people at risk for developing active tuberculosis."

Worldwide, TB is the most common serious opportunistic infection in people living with HIV. In 2016, it accounted for 40 percent of deaths among people living with HIV, according to the World Health Organization (WHO). An estimated one-quarter of the world’s population has latent TB infection.

A person with latent TB is infected with tuberculosis-causing bacteria but does not have any symptoms of the disease. Among people with latent infection, the treatment recommendation is TB prophylaxis for adults and adolescents living with HIV who have either had a positive test for latent TB or have an unknown TB status and who do not have active TB.

HIV infection is the greatest risk factor for progression to active TB disease. Skin or blood tests can detect latent TB infection, but may not be readily available in resource-limited areas. WHO guidelines recommend TB prophylaxis for adults and adolescents living with HIV who have either had a positive test for latent TB or have an unknown TB status and who do not have active TB.

Prophylactic antibiotic therapy to stop active TB from developing is effective, but current preventive regimens are lengthy, can be difficult for people to complete, and carry the risk of side effects such as liver damage. A six-to nine-month course of daily isoniazid has been the standard in many TB-endemic countries, although WHO recommendations include different options ranging up to 36 months in length for people living with HIV. Prior preclinical studies had suggested that an ultra-short course of treatment may be as effective as a longer regimen. Researchers suspected that it also may increase treatment adherence.

Between 2012 and 2014, the ACTG 5279 study enrolled 3,000 people 13 years of age and older living with HIV in Botswana, Brazil, Haiti, Kenya, Malawi, Peru, South Africa, Thailand, the United States and Zimbabwe. Participants either lived in an area with a high TB burden or had had a skin or blood test indicating latent TB infection. When they entered the study, approximately half of participants were taking antiretroviral therapy to treat their HIV.

At the time of study enrollment, decisions on when to start antiretroviral therapy typically were based on a person’s CD4+ cell count — a measure of immune system health. Current WHO guidelines recommend that all people living with HIV begin antiretroviral treatment as soon as possible after diagnosis, regardless of CD4+ cell count.

Study participants were randomly assigned to a one-month course of rifapentine and isoniazid or a nine-month course of isoniazid. Investigators monitored the participants for an average of three years.

Overall, TB incidence was lower than expected and was similar in both treatment arms, with 32 participants assigned to the one-month regimen and 33 to the nine-month regimen developing active TB disease. Regardless of treatment type, TB rates were higher among participants who were not on antiretroviral therapy at the start of the study and among those who had had a positive TB skin or blood test.

For participants with low CD4+ cell counts — indicating an immune system weakened by HIV infection — at the start of the study, more cases of active TB occurred among those receiving the short-course treatment compared to the standard regimen. However, this difference was not statistically significant, meaning it might have been due to chance.

Treatment adherence was significantly better for the shorter regimen. Nearly all (97 percent) of those assigned to the short-course therapy completed the full antibiotic course, compared to 90 percent of participants in the nine-month arm.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

For more information about the study, visit ClinicalTrials.gov using identifier NCT01404312. For more information about ACTG, see ACTGNetwork.org.

Reference: S Swindells et. al. One month of rifapentine/isoniazid to prevent TB in people with HIV: Brief-TB/A5279. Oral presentation at the 2018 Conference on Retroviruses and Opportunistic Infections, Boston, Ma.

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Video & audio soundbites and B-roll

This dropbox provides folders for audio and video soundbites

https://www.dropbox.com/sh/tdernemaseapc8v/AAB0gBO9TGwicwtEkE8fNSi5a?dl=0

Susan Swindells, M.B.B.S., University of Nebraska Medical Center Department of Internal Medicine professor and medical director of the HIV Clinic, is lead author of the study.

Video soundbites

What is the benefit of the one-month versus nine-month therapy?

Location- :0-:22 seconds

Well we know that the people who are prescribed the nine-month therapy, very many of them don’t complete it because they basically feel well, they have this latent infection and so it’s hard to persuade the people to keep taking their medicine if they don’t feel bad so a lot of people just quit early and we’re hoping that one month that will be easier to take.

What is the next step?

Place mark- :24-:39 seconds

Well, it needs to get approved by regulatory affairs authorities like the FDA, WHO and so forth and peoples’ insurance can pay for it and we’re hoping the state TB [tuberculosis] program will adopt it and make it available to people.

What did the study find?

Place mark- :41-:55

We found that taking rifapentine with isoniazid for one month daily was both safe and effective in preventing progressions of TB [tuberculosis] disease in people who have latent infection.

What did you do in the study?

Place mark-:56-1:16

So we did the study, compared the one month regimen to the standard nine-month therapy which is isoniazid on its own and we found in both groups we had equal numbers of TB [tuberculosis]  cases. They were exactly the same so our regimen of one month over a short course was as effective as the longer one.

What is the impact of TB [tuberculosis]?

Place mark- 1:17-1:38

So if you have HIV you have 10 times more risk of getting disease than someone who doesn’t. And annually, ten million people get TB [tuberculosis] disease and one-and-a-half million people die every year which is more that one thousand people per day so globally this is a huge problem.

Why are people with HIV more susceptible to TB [tuberculosis]?

Place mark- 1:39-2:01

So HIV-infected patients are more susceptible because of the damage to their immune system from the HIV so TB [tuberculosis] is one of the things that takes advantage of that can make them very ill and a lot of people die from that so TB [tuberculosis] globally is the biggest killer of HIV. More people die of that than anything else.

What is the next step?

Place mark- 2:02-2:22

So the next steps is to study this in people who don’t have HIV and make sure it works just as well there and also our study didn’t include children under thirteen and so they’re another vulnerable population and we need to study it there and make sure that it works and that we have proper formulations that children can take.

Audio soundbites

What did you do in the study?

So we did the study, compared the one month regimen to the standard nine-month therapy which is isoniazid on its own and we found in both groups we had equal numbers of TB [tuberculosis]  cases. They were exactly the same so our regimen of one month over a short course was as effective as the longer one.

What is the benefit of the one-month versus nine-month therapy?

Well we know that the people who are prescribed the nine-month therapy, very many of them don’t complete it because they basically feel well, they have this latent infection and so it’s hard to persuade the people to keep taking their medicine if they don’t feel bad so a lot of people just quit early and we’re hoping that one month that will be easier to take.

What is the impact of TB [tuberculosis]?

So if you have HIV you have 10 times more risk of getting disease than someone who doesn’t. And annually, ten million people get TB [tuberculosis] disease and one-and-a-half million people die every year which is more that one thousand people per day so globally this is a huge problem.

What is the next step?

So the next steps is to study this in people who don’t have HIV and make sure it works just as well there and also our study didn’t include children under thirteen and so they’re another vulnerable population and we need to study it there and make sure that it works and that we have proper formulations that children can take.

B-roll (Dr. Susan Swindells in clinic with HIV patient, researchers working in HIV laboratory, lab equipment working

Bottle of Isoniazid medication and B-6 vitamin side-by-side (B-6 is taken with it)

Place mark- 2:27-2:42

 

Bottle of Isoniazid medication alone

Place mark- 2:43-3:01

 

Bottle of Isoniazid medication and B-6 vitamin (B-6 is taken with it)

Place mark- 3:01-3:15

 

Side of bottle of Isoniazid medication

Place mark- 3:16-3:41 then side of bottle and front of bottle

 

Bottle of Isoniazid medication in foreground and B-6 vitamin in background (B-6 is taken with it)

Place mark- 3:41-3:52

 

Bottle of B-6 vitamin (B-6 is taken with Isoniazid)

Place mark- 3:53-4:06

 

Dr. Susan Swindells at the University of Nebraska Medical Center with an HIV patient in clinic talking then check-up with patient.

Wide shot and close-ups

Place mark- 4:08-5:02

 

People working in Dr. Susan Swindells’ research laboratory and lab equipment operating, test tubes being used,

Wide shots then close-ups

Place mark-5:03-6:47