Kelly E. Dooley
SEATTLE — A short-course drug regimen to prevent tuberculosis was found to be safe in patients with HIV on dolutegravir therapy, while not reducing the HIV drug’s effectiveness, according to study results presented at CROI.
Researchers said the once-weekly combination of rifapentine and isoniazid (3HP) has the potential to “transform TB control,” but noted that a previous study exploring its use with dolutegravir (DTG) was halted after two of the four healthy participants experienced serious adverse events.
“Dolutegravir has recently been recommended by WHO as first-line therapy for treatment-naive patients with HIV infection, and similarly, WHO recently recommended ... use of 3HP — [a] once weekly dosing of rifapentine and isoniazid for 12 total doses — for treatment of latent tuberculosis in patients with high incidence of tuberculosis,” Kelly E. Dooley, MD, PhD, MPH, associate professor of medicine at Johns Hopkins University School of Medicine, said at a news conference.
In the study presented at CROI, the researchers recruited 60 HIV-infected adults in South Africa (70% female; median age, 40 yeas) with undetectable viral load on efavirenz (EFV)-based regimens. All participants were black Africans.
The participants received 50 g DTG once a day in place of EFV for 8 weeks, then began 3HP. After completion of 3HP, the researchers followed the participants for 4 more weeks. They measured viral loads at baseline and at weeks 11 and 24.
Dooley said they measured pharmacokinetic and safety data of the first 12 participants in the study to determine the dose for the subsequent groups of patients.
The participants’ median CD4 was 683 cells/mm3 and the median BMI was 28.9 kg/m2. At the time of the report, all patients had received at least six 3HP doses.
The researchers reported three grade 3 adverse events, including two elevated creatinine and one hypertension event. There were no hypersensitivity-type reactions with grade 3 or higher, Dooley said.
According to Dooley and colleagues, HIV viral loads at baseline, day 58 (pre-3HP), days 72 (third 3HP dose) and day 168 (post-HP) were less than 40 copies/mL Administration of 3HP decreased DTG bioavailability by 29%, the researchers wrote.
“We were quite reassured and happy to see that drug concentrations seemed to be at effective concentrations without having to double the dose, that safety was quite nice, albeit for only 60 people, and biologic suppression was maintained by all patients on our study,” Dooley said.
Study researcher Gavin Churchyard, MBBCh, PhD, MMed, group CEO of the Aurum Institute, called preventive therapy for TB “a critical component of any effort to control the TB epidemic,” but noted that current treatment options are too long and potentially toxic.
“These findings will allow us to move forward with coadministration of 3HP and DTG, offering the best treatment options to those who need it the most.” – by Bruce Thiel
Dooley KE, et al. Abstract 80LB. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2019; Seattle.
Disclosures: Churchyard is an employee of the Aurum Institute. Dooley reports no relevant financial disclosures.