We found that, at the manufacturer-recommended threshold for latent infection (≥0·35 IU/mL), the IFN-γ release assay was not able to differentiate between people living with HIV who had been exposed to M tuberculosis but were able to control infection, from those who will progress to disease over 15 months, which might result in either unnecessary treatment or missed opportunities to prevent progression to disease. This evidence concerns the gene IFNG and disease arising from reactivation of latent virus.