One third of the world’s population is estimated to be infected with
Mycobacterium tuberculosis
, representing a huge reservoir
of potential tuberculosis (TB) disease. Risk of progression to active TB is highest in those with HIV coinfection. However, the
nature of the host-pathogen relationship in those with “latent TB infection” and how this is a
ff
ected by HIV coinfection are poorly
understood. The traditional paradigm that distinguishes latent
infection from active TB as distinct compartmentalised states is
overly simplistic. Instead the host-pathogen relationship in “latent TB infection” is likely to represent a spectrum of immune
responses, mycobacterial metabolic activity, and bacillary nu
mbers. We propose that the impact of HIV infection might better
be conceptualised as a shift of the spectrum towards poor immune co
ntrol, higher mycobacterial metabolic activity, and greater
organism load, with subsequent increased risk of progression to active disease. Here we discuss the evidence for such a model and
the implications for interventions to control the HIV-associated TB epidemic.