TB Manual

ART is strongly recommended for all people with HIV who also have TB.²³ The optimal timing of ART initiation in people receiving TB treatment, balancing the risk of progressive HIV and TB disease with the risk of immune reconstitution inflammatory syndrome (IRIS), has been evaluated in nine randomized-controlled trials.^36–38 Two systematic reviews of these trials concluded that early initiation of ART, within 2 weeks of TB therapy initiation, reduces overall mortality and the incidence of additional acquired immunodeficiency syndrome (AIDS)-defining illnesses. The benefit of early initiation of ART was most apparent in patients with CD4 counts of <50 × 10⁶/L.

As an important caveat, early initiation of ART in cases of central nervous system (CNS) TB may be hazardous, probably because of the unique risks of IRIS reactions in the closed space of the cranium. One randomized study of TB meningitis compared immediate ART with a 2-month delay in ART initiation and found higher rates of severe adverse effects in the immediate ART group. However, the mortality rate, which was more than 50%, did not differ between arms.³⁹ Thus, in those with CNS-TB, the optimal time to initiate ART is not well-established. Delaying therapy at least 2 weeks after initiation of TB treatment appears to provide the best balance between avoiding cerebral complications of IRIS and improved TB treatment outcomes (see Chapter 7: Extra-pulmonary Tuberculosis).

In patients already receiving effective combination ART at the time of the TB diagnosis, ART should be continued. However, a change in ART regimen may be required to accommodate potential drug interactions with rifamycins. Note that when an ART dose adjustment is made to address an interaction with a rifamycin, the increased dose should be maintained for 2 weeks after stopping the rifamycin to allow for the liver enzyme induction effect to wear off.

Recommendations

• We strongly recommend initiating antiretroviral therapy within 2 weeks of starting TB therapy, provided there is no documented central nervous system TB (good evidence).

• We conditionally recommend delaying antiretroviral therapy (ART) initiation for at least 2 weeks after initiation of anti-TB treatment for those with central nervous system TB, although here the optimal time to initiate ART is less well-established and expert consultation is advised (poor evidence).

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