Ending Tuberculosis with Preventive Therapy

Highlights:

  • One month course
    of rifapentine plus isoniazid was comparable to single agent isoniazid
    treatment for nine months to prevent tuberculosis infection in HIV
    patients as per a recent randomized trial
  • Preventive
    therapy, especially in high-risk groups such as HIV infected patients is one of the key
    strategies to eradicate tuberculosis, but current preventive regimens last
    for several months and patient compliance is poor
  • Tuberculosis
    remains the leading killer among infections. Despite TB programs achieving
    reduced death rates and being cost-effective, there has been no noticeable impact on the global
    incidence of TB

Short one-month regimen of rifapentine plus
isoniazid is equally effective in preventing TB infection in HIV infected
patients as the current standard regimen of isoniazid alone for 6-9 months
according to a recent randomized trial published in the New England Journal of Medicine.

Testing
Efficacy of Shorter Regimens

Since the standard preventive TB regimen last 6-9 months and
associated with poor treatment completion rates, the search has been on for
shorter courses without compromising on efficacy. This prompted the current
randomized trial testing the efficacy of a one month course of rifapentine plus
isoniazid versus the standard isoniazid for up to nine months.

  • The randomized
    trial dubbed Brief
    Rifapentine-Isoniazid Efficacy for TB [Tuberculosis] Prevention/A5279
    trial
    was conducted in 10 countries in across Africa, Asia, Caribbean,
    South America, and North America from May 2012 to November 2014. All
    patients were followed up until November 2017, which was about three years
    after the last patient had been enlisted
  • All participants had confirmed HIV
    infection
    , older than 13 years, and either lived in an area with
    a TB prevalence of at least 60 cases per 100,000 population or tested
    positive for latent tuberculosis
  • Average age of
    participants was 35 years and 54 percent were females
  • About half of the
    patients were receiving antiretroviral
    therapy
    (ART) at onset of the study, and 75 percent of these patients had no detectable viral load.
  • Overall, 1,488
    participants were randomly assigned to receive a 1-month course of
    rifapentine plus isoniazid, while 1,498 patients were randomly assigned to
    receive 9 months therapy of isoniazid alone
  • Participants were
    followed up every 4 weeks for 36 weeks followed by once every 12 weeks
    thereafter for an average of about 3 years
  • Patients were
    given antiretroviral therapy (ART) with efavirenz or nevirapine for the
    first month, following which the use of other ART was allowed

Key Findings
of Study

  • The primary
    endpoint namely first detection of tuberculosis infection or death due to
    tuberculosis — was reported in two percent of patients in the one-month group and two percent of patients in the 9-month control group
  • Patients assigned
    to the 1-month combination treatment reported fewer adverse events, and
    were more likely to finish the full treatment than the control group

The
findings of the study indicate that one month rifapentine-isoniazid combo is
equally effective in preventing TB in high
-risk patients and treatment completion rates are high.

‘Tuberculosis preventive therapy (treating asymptomatic latent tuberculosis infection) is highly effective, especially in patients with HIV infection, and significantly reduces death rates. One-month combination treatment of isoniazid plus rifapentine had fewer side effects and patients were more likely to complete treatment and this regimen may be useful in ending the tuberculosis scourge.’
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Possible
Limitations of Study & Future Plans

  • The study enrolled only adults who were not pregnant or breastfeeding and
    adolescents (≥13 years of age) with HIV infection. Hence, the efficacy of the
    1-month regimen in
    younger children, pregnant women and HIV uninfected persons who are at
    increased risk needs to be investigated
  • The study did not
    include data from more recent studies that showed an independent benefit
    of antiretroviral therapy in the prevention of TB. Approximately 50
    percent of patients in the current study were on ART at
    onset of the trial, and more
    than 90 percent were
    receiving ART by trial completion
  • Although rifapentine-containing regimens are effective in TB, the cost
    of rifapentine may be an important hurdle to implementation
    of this
    regimen in low-income settings
    where TB is common. Measures must
    be taken to bring down the cost of the drug
  • Prior studies
    have shown that co-administration of isoniazid and rifapentine with
    efavirenz did not significantly impact efavirenz concentrations, but
    further studies are needed to find out about interactions of TB treatment
    with more contemporary antiretroviral agents, such as integrase strand
    transfer inhibitors, for example, dolutegravir

Summary

In conclusion, the findings of the study confirmed that one
month of daily rifapentine plus isoniazid was comparable in efficacy to nine
months of isoniazid in TB prevention in high-risk patients such as those with
HIV infection, which has been predicted in prior mouse model studies

Matthew J. Saunders, MRCP, of University College London in
England, and Carlton A. Evans, PhD, of Universidad Peruana Cayetano Heredia in
Peru, and an accompanying editorial  said: “Improving the brevity, acceptability,
and safety of preventive therapy is important and will potentially have a major
effect
. However, such therapy has to
be considered in the context that several billion people
… are believed
to have asymptomatic latent tuberculosis infection.”

References :

  1. Ending Tuberculosis through Prevention – (https://www.nejm.org/doi/full/10.1056/NEJMe1901656?query=featured_home)

Source: Medindia