Single round of 3HP safe, effective for PLWH on ART
A weekly tuberculosis prevention regimen of isoniazid 900 mg and rifapentine 900 mg for 12 weeks resulted in higher treatment completion rates among patients with HIV in South Africa, Ethiopia and Mozambique compared with daily isoniazid for 6 months, according to findings from CROI.
However, annual treatment with this regimen — called 3HP — in settings with high tuberculosis transmission did not result in a greater benefit for patients on ART, the study results demonstrate.
“Currently, tuberculosis (TB) rates are high in people living with HIV, including those on ART,” Gavin Churchyard, MBBCh, FCP (SA), MMed, PhD, group CEO of the Aurum Institute and lead investigator on the study, told Healio. “In fact, in 2018, 64% of notified TB patients had a documented HIV test result. A total of 477,461 TB cases among HIV-positive people were reported, of whom 86% were on antiretroviral therapy. 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.”
He added, “We know that TB preventive therapy reduces the risk of TB, but past studies have shown that its effect wanes rapidly in high TB transmission settings.”
Churchyard and colleagues enrolled people living with HIV (PLWH) in South Africa, Ethiopia and Mozambique aged 2 years and older in the study. Patients did not have active TB and were on ART for more than 3 months. The researchers randomly assigned them 9:9:2 to periodic, or annual, treatment with weekly isoniazid 900 mg and rifapentine 900 mg for 12 weeks [periodic 3HP (p3HP)], 3HP or 6 months of daily isoniazid (6H) to determine if a short course of TB preventive therapy annually provided more durable protection than providing the treatment only once, Churchyard told Healio.
According to the study, participants in the 3HP/p3HP and 6H arms were followed for 24 and 12 months, respectively. All participants were screened for TB with symptoms, chest X-ray and sputum culture after 12 and 24 months and treatment completion was tracked using pill counts for the combined 3HP/p3HP arms vs. the 6H arm. Researchers then tracked and compared TB incidence and all-cause mortality over 12 months in the 3HP and 6H arms, as well as TB incidence, all-cause mortality and permanent discontinuation of 3HP for adverse events over 24 months in the p3HP and 3HP arms.
From November 2016 to November 2017, 4,593 participants were screened for TB; 4,027 were enrolled and 4,014 were analyzed. The median age of patients was 41 years and 70% were women. Most participants (63%) were from South Africa; 22% were from Ethiopia and 15% were from Mozambique. All were on ART.
According to the study, treatment completion in the combined 3HP (n = 3,610) and 6H (n = 404) arms was 90.4% compared with 50.5% (RR, 1.79; 95% CI, 1.62-1.79). TB incidence and mortality from month 0 to month 12 was similar in the 3HP and 6H arms. TB incidence over 24 months and from month 12 to month 24 was similar in the p3HP (n = 1,808) and 3HP (n = 1,802) arms.
“The study had three key findings,” Churchyard said. “First, we know that 3HP in people living with HIV infection who are receiving ART is safe. Second, we found that a single round of 3HP is as effective as taking it annually. Finally, we found that 3HP has far higher treatment completion rates than the longer standard course of isoniazid alone, taken daily for 6 months.”
Over 24 months, TB prevalence among QuantiFERON-TB GOLD Plus positive participants, rate of rifampicin-resistant TB and mortality were similar in the p3HP and 3HP arms. Treatment discontinuation in the p3HP and 3HP arms was 1.2% vs. 0.6% (OR, 2.11; 95% CI, .095-5.02).
“Based on this and other study results, we are now catalyzing the scale-up of 3HP globally through the IMPAACT4TB project to contribute to ending the TB epidemic,” Churchyard told Healio. “We are also doing further research to determine the best dose of 3HP in children and evaluating novel models of delivery to support scale-up.” – by Caitlyn Stulpin
Churchyard G, et al. Abstract 143LB. Presented at: Conference on Retroviruses and Opportunistic Infections; March 8-11, 2020; Boston.
Disclosure: Churchyard reports receiving a provision of equipment from Sanofi.