HomeThe 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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