Johns Hopkins Medicine researchers are attending the annual Conference on Retroviruses and Opportunistic Infections (CROI), where they are sharing their latest findings in the ongoing battle against HIV/AIDS and related infectious diseases with other top basic, translational and clinical researchers from around the world. This year’s conference is being held March 4 to 7 at the Washington State Convention Center in Seattle.

The following four oral abstracts will be presented during the session Oral Abstract O-07 TB: From Contact to Cure and Beyond in room 6AB. Separate embargo-lift times are noted for each presentation.

TB PREVENTION FOR PREGNANT WOMEN WITH HIV
 

IPT and Pregancy Outcomes in HIV-Positive Women, the Tshepiso Cohor

Both pregnancy and HIV increase the risk of tuberculosis, which can lead to poor birth outcomes. A previous study showed that isoniazid preventive therapy given during pregnancy led to higher risk of bad outcomes than administering isoniazid post-delivery. Nicole Salazar-Austin, M.D., assistant professor of pediatrics and infectious disease at the Johns Hopkins University School of Medicine, will present results from the Tshepiso cohort, a prospective observational study of 152 mother-infant pairs from 2011 to 2014 in Soweto, South Africa. The research team found that isoniazid preventive therapy given during pregnancy was not associated with a higher rate of poor maternal or infant outcomes.

OK TO COMBINE TB PREVENTIVE REGIMEN WITH ANTIRETROVIRALS
 

Safety of Weekly Rifapentine/Isoniazid (3hp) for Adults With HIV on Dolutegravir

So-called short course preventive therapy for latent tuberculosis infection is preferred because of convenience and higher likelihood that patients will complete treatment. However, a previous, small trial testing in healthy adults the safety of short course therapy in combination with the antiretroviral dolutegravir resulted in fever, hypertension and other problems. Kelly Dooley, M.D., Ph.D., M.P.H., associate professor of medicine and clinical pharmacology at the Johns Hopkins University School of Medicine, will present the results of a 60-participant trial during which adults infected with HIV who were on dolutegravir were given 12 once-weekly rifapentine/isoniazid doses, also known as 3HP. The study team finds that the coadministration of dolutegravir and 3HP was well tolerated and thus could transform TB control in the long term.

OPTIMAL DOSE ESTABLISHED FOR HIGH DOSE ISONIAZID IN TREATING MDR-TB

Early Bactericidal Activity of High-Dose Isoniazid Against Multidrug-Resistant TB

While the World Health Organization (WHO) recommends high dose isoniazid in treating multidrug-resistant tuberculosis, the optimal dose and how well it works has not until now been established. The AIDS Clinical Trials Group A5312 enrolled 59 participants to receive randomized doses of the drug for seven days. The 43 trial participants with isoniazid resistant TB conferred by a genetic mutation in the inhibin subunit alpha (INHA) gene received 5, 10 or 15 milligram per kilogram of the drug, and the 16 drug responsive patients received the standard 5 milligram per kilogram dose. Sputum cultures were collected daily and analyzed for bacterial activity. Kelly Dooley, M.D., Ph.D., M.P.H., associate professor of medicine and clinical pharmacology at the Johns Hopkins University School of Medicine, will present data showing that 10–15 milligram per kilogram doses had substantial impact on Mycobacterium tuberculosis with INHA mutations, similar to lower doses on strains without INHA mutations. These results support WHO recommendations for treating patients with INHA strains.
 

NEW-GENERATION TB DRUGS ARE SAFE FOR THE HEART

QT Effects of Bedaquiline, Delamanid or Both in MDR-TB Patients: The Deliberate Trial

Two of the first new drugs to be approved in 40 years for treating tuberculosis are well tolerated, but the body processes them very slowly, and they affect the length of the heartbeat in ways that could potentially cause fast and chaotic heartbeats, seizures or fainting, or could cause the heart to stop. Kelly Dooley, M.D., Ph.D., M.P.H., associate professor of medicine and clinical pharmacology at the Johns Hopkins University School of Medicine, will present results of the AIDS Clinical Trials Group A5343, which treated 84 adults with multidrug-resistant TB who were receiving multidrug background treatment of bedaquiline, delamanid or both drugs for 24 weeks. Each participant’s heart performance was measured with electrocardiograms at the beginning, every two weeks for 24 weeks and at week 28. The team found that the combined effect of bedaquiline and delamanid is clinically modest, and they are safe to use for MDR-TB patients with normal heartbeats.

On the Web:

• Child with Drug-Resistant TB Successfully Treated at Johns Hopkins Children’s Center