New results from a large international study using a simplified approach to prevent TB have the potential to dramatically improve outcomes for HIV positive people, cutting prophylaxis from nine months to one.
The BRIEF-TB study randomised 3000 adults with either latent TB or at high risk of TB infection to either one month of daily isoniazid (H) 300 mg plus rifapentine (P) 450-600 mg or to the standard of care nine-month regimen with daily isoniazid 300 mg.
The study included three years follow-up with primary endpoints of incidence rates (IR) of active TB, TB death or death by unknown cause, and stratified participants by ART use.
This was a non-inferiority study with lower margin of 1.25/100 patient years, based on an assumed IR of 2.0/100 PY in the nine-month arm. Results were presented by Richard Chaisson from Johns Hopkins University.
The study recruited participants from May 2012 to November 2011 in 45 sites in 10 countries.
Baseline demographics included 54% women (n=1614), median age 35 years (IQR 28-43), with 66% black and 24% Hispanic. Median CD4 count was 470 cells/mm3 (IQR 346 to 635) and 50% were on ART at entry. Median BMI was 23.5 (IQR 20.9 to 27.1). Approximately 20% (n=634) had latent TB defined by positive TST or IGRA.
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After three years of follow-up, there were no significant difference in the rate of primary events: in 34 vs 35 participants in the one vs nine month arms respectively. TB incidence rates were 0.69 vs 0.72/100 person years respectively (difference -0.025, upper 95% CI: 0.31).
Rates were higher for participants not on ART at entry and those with a positive TST/IGRA, but with no difference between treatment arms. Higher incidence in the one-month arm with baseline CD4 count <250 cells/mm3 was not statistically significant (p=0.12). See Table 1.
Although higher serious adverse events in the nine-month arm (7.1% vs 5.6%) were not statistically significant (p=0.1), targeted safety events was significantly lower with one month treatment (3.3 vs 5.1/100 person years , p=0.03). Importantly the one-month course was more likely to be completed (97% vs. 90%, p<0.01).
There was one case of rifampin-resistant TB in each arm and one case of izoniazid-resistant TB in the nine-month arm.
The researchers concluded that once daily izoniazid plus rifampentine was non-inferior to nine-months izoniazid, with fewer side events, and higher completion rates.
|Table 1: Incidence of Primary Events by Baseline Characteristics|
Event / PY
Event / PY
|IR difference: 1-9 month|
All p=NS between groups
(-0.30 to +0.35)
0.005 (-0.43 to +0.44)
-0.059 (-0.55 to +0.44)
-0.066 (-0.90 to +0.77)
-0.01 (-0.36 to +0.34)
|Baseline CD4 (copies/mm3)|
1.15 (-0.30 to +2.59)
-0.19 (-0.51 to +0.12)
-0.22 (-0.68 to +0.24
0.15 (-0.33 to +0.62)
The effectiveness of current TB prophylaxis for people with HIV is limited by the difficulties of taking nine months of isoniazid -- despite their dramatically higher need for this protection.
These results are likely to change management of HIV in people with latent TB or in high TB incidence settings.
Swindells S et al. One month of rifapentine/isoniazid to prevent TB in people with HIV: BRIEF-TB/A5279. CROI, 4-7 March 2018. Late breaker oral abstract 37LB.
[Note from TheBodyPRO: This article was originally published by HIV i-Base on March 5, 2018. We have cross-posted it with their permission.]