Continuous isoniazid for the treatment of latent tuberculosis infection in people living with HIV

Objective: This systematic review was carried out to determine the effectiveness of continuous isoniazid (given for at least 36 months) for the treatment of latent tuberculosis infection (LTBI) in people living with HIV (PLHIV). Methods: Six databases and HIV and tuberculosis (TB) conference abstract books were searched for randomized controlled trials that compared the effectiveness of continuous isoniazid with 6 months of isoniazid. Outcomes of interest were TB incidence, mortality, adverse events and risk of drug resistance. Data were pooled using fixed-effects meta-analysis. Results: Three studies were included, from Botswana, South Africa and India. The risk of active TB was 38% lower among patients receiving continuous isoniazid compared with isoniazid regimen for 6 months [relative risk (RR) 0.62, 95% confidence interval (CI): 0.42-0.89; I-2 = 0%], and 49% lower for those with a positive tuberculin skin test (TST) (RR 0.51, 95% CI: 0.30-0.86; I-2 = 7%). Similarly, individuals with positive TST had a 50% lower chance of death (RR 0.50, 95% CI: 0.27-0.91; I-2 = 3%). Two studies found no evidence of an increase in adverse events in the continuous isoniazid group, whereas a third study, that used a different definition for adverse events, found strong evidence of increase. There was no evidence of increased drug resistance when continuous isoniazid was given. Conclusion: For PLHIV in settings with high TB and HIV prevalence and transmission, continuous isoniazid for at least 36 months is beneficial and probably outweighs the risk of increased adverse events compared with an isoniazid regimen for 6 months.