The regimens described in the following sections are not recommended for general use in Canada but can be considered when other alternatives are not viable.
3.3.1. Twice-weekly isoniazid for nine months
Twice-weekly INH has been evaluated in 2 small trials, both in HIV-infected individuals and both using a 6-month regimen.40,41 Both studies demonstrated a significant reduction in active TB compared to placebo.40,41 In another trial among young children with HIV, up to 24 months of thrice-weekly INH showed similar efficacy compared to daily INH and improved efficacy compared to placebo.42 However, power was limited because the trial was stopped early as a result of a very high rate of active TB in the placebo arm.42 Recent observational studies in Iqaluit, Nunavut, have shown relatively high rates of completion among patients treated with 9 months of twice-weekly INH by DOT. Although this regimen showed a trend toward lower completion compared to 3HP, the difference was not statistically significant.43,44
Twice-weekly INH is not a preferred TPT regimen but can be considered when other regimens are not feasible. The CDC continues to support its use (see Table 1) as an alternate regimen.16
Good practice statement
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Given the uncertainty regarding treatment efficacy and the relatively increased importance of each dose compared to daily regimens, twice-weekly isoniazid regimens should be given via DOT over a 9-month duration.
3.3.2. Isoniazid and rifampin daily for three months (3HR)
Although small, trials comparing 3 or 4 months of INH and rifampin to 6 or 12 months of INH have found a similar incidence of active TB in both HIV-uninfected45–48 and HIV-infected populations38,49 and network meta-analyses support efficacy compared to placebo.9,10 Adverse events, including drug discontinuations and hepatotoxicity, have been similar with 6 or 12 months INH or 3-4HR in HIV-uninfected populations,45,48 whereas drug discontinuations have been higher in those taking 3-4HR in some studies in HIV-infected populations.38,49
Thus, the 3HR regimen does not confer any advantage in terms of efficacy, safety or treatment completion in comparison to the mono-INH regimens that are now recommended as second-line regimens. Furthermore, the 3HR regimen also carries the same risk of drug-drug interactions as 4 R and 3HP. Given this, we suggest that the role of this regimen for TPT in Canada is very limited.
Table 1. Summary of recommended treatment regimens for latent tuberculosis infection.
Regimen | Duration | Dose | Frequency | Common adverse effects |
---|---|---|---|---|
First-line regimens | ||||
Rifapentine and isoniazid (3HP) | 3 months (12 doses) | Isoniazid: 15 mg/kg Maximum: 900 mg Rifapentine: 10-14.0 kg: 300 mg 14.1-25.0 kg: 450 mg 25.1-32.0 kg: 600 mg 32.1-49.9 kg: 750 mg ≥50.0 kg: 900 mg Maximum: 900 mg |
Once weekly | Flu-like reactions, drug interactions |
Rifampin (4 R) | 4 months (120 doses) | 10mg/kg Maximum: 600 mg |
Daily | Rash, drug interactions |
Second-line regimen | ||||
Isoniazid (9H) | 9 months (270 doses) | 5mg/kg Maximum: 300 mg |
Daily | Hepatoxicity, peripheral neuropathy |
Alternative regimens | ||||
Isoniazid (6H) | 6 months (180 doses) | 5mg/kg Maximum: 300 mg |
Daily | Hepatoxicity, peripheral neuropathy |
Intermittent isoniazid for 9 months | 9 months (78 doses) | 15mg/kg Maximum: 900 mg |
Twice weekly | Hepatoxicity, peripheral neuropathy |
Isoniazid and rifampin (3HR) | 3 months (90 doses) | Isoniazid: 5mg/kg Maximum: 300 mg Rifampin: 10mg/kg Maximum: 600 mg |
Daily | Hepatoxicity, peripheral neuropathy, drug interactions |
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