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• Aim of Study

• Method
– Type of study design
– Number of sample
– intervention
• Baseline characteristic
– Table hasil utama sesuai aim of study
• Short discussion
• conclusion
Daily vs Intermittent Antituberculosis
Therapy for Pulmonary Tuberculosis in
Patients with HIV
A Randomized Control Trial

Jama Internal Medicine


• WHO (2009) recommend
– Daily, or
– Part-daily (daily in intensive phase alone)
antituberculosis therapy (ATT)
• Revised national TB Control Program in India
– Thrice-weekly regimen until 2016
– Cure rates
• 83% and 90% among HIV-positive parients with TB, before
and afer the era of ARV,
• compared with 96% among HIV-negative patients with TB
Question
• Is daily antituberculosis therapy superior to
thrice-weekly dosing in reducing failures and
acquired rifampicin resistance among HIV-
positive patients with culture-confirmed
pulmonary tuberculosis in the era of
antiretroviral therapy?
Methods
Study design and time
– RCT
– Conducted in National Institute for Research in
Tuberculosis, Chennai, Vellore, and Madurai, South
India
– Between September 14, 2009, and, January 18,2016
• Randomization
– Patients fullfilling the clinical and laboratory criteria
were randomly allocated 1:1:1 to the 3 ATT regimens
– Stratification was based on
• Baseline CD4 lymphocyte <150 cells/mcL vs ≥150 cells/mcL
• Sputum smear grading of 0 and 1+ vs 2+ and 3+
Inclusion and exclusion Criteria

• Participants • Excluded Criteria


– Adult aged 18 years or older – Patients taking protease
– HIV positive inhibitor-based ART
– Newly diagnosed with – Hypersensitivity or resistance
pulmonary TB by either to rifampicin
smear test or Xpert MTB/RIF – Pregnant or lactating women
test – Having major psychiatric
illness
– Had significant liver or renal
function abnormalities
• Intervention
– 3 ATT regimens were
• Daily (in both intensive and continuation phase)-
2RHZE7/4RH7
• Part-Daily ( daily in intensive phase and intermittent
continuation phase)-2RHZE7/4RH3
• Intermittent (thrice weekly throughout)-2RHZE3/4RH3
• Outcome Measures
– Favorable responses
• Treatment completion
• Negative sputum cultures collected during the last 2 months
of treatment
– Unfavorable responses
• Bacteriological failures (with or without emergence of ARR)
• Clinical failures (mandating change or restart of regimen)
• Deaths (all-cause of mortality), escept unnatural death
• Toxic effects necessitating permanent substitution of
allocated regimen
• Patients who dropped out (irretrievable >6 weeks)
Statistical Analysis
• To adjust for multiple comparisons, the
Bonferroni correction was applied, taking a
two-sided P value of .025 as the significance
level.
Results
• Of 331 patients
– 251 (76%) male
– Mean age 39 years
– Mean HIV viral load 4.9 log10 copies/mL
– Median CD4 lymphocyte count 138 cells/mcL
• Favorable responses
– 91% (89 of 98) in daily regimens
– 80% (77 of 96) in part-daily regimens
– 77% (75 of 98) in intermittent regimens
• Total 18 patients died
• Total 18 patients dropped out during treatment
• Six, 4, and 6 patients had TB recurrence in daily, part-daily, and
intermittent regimens respectively
Results
• Hepatotoxic effects
– 9% in daily regimen
– 2% in intermittent regimen
• Acquired rifampicin resistance emerged only
in group receiving intermittent
antituberculosis despite ARV
Conslusions
• Daily anti-TB regimen proved superior to a thrice-weekly regimen in
terms of efficacy and emergence of rifampicin resistance.
• The part-daily regimen did not confer any advantage over an
intermittent regimen with regard to efficacy or tolerability but
preventedARR.
• AhigherCD4lymphocytecount (≥150 cells/μL ) at the end of the
intensive phase, rather than at baseline, was associated with a
successful outcome.
• Daily administration of antituberculosis therapy resulted in higher
cure rates and prevented acquired rifampicin resistance compared
with a thrice-weekly regimen, but with slightly higher
hepatotoxicity, which was manageable under trial conditions.