Disseminated HIV-associated tuberculosis is deadly: Can treatment for this condition be improved?

Many patients hospitalised with HIV infection and tuberculosis (TB) die despite receiving standard TB treatment; most have TB that has spread from their lungs to their blood and other organs (“disseminated TB”).

Current TB treatments were originally developed for use in HIV-negative people with TB lung disease. But disseminated HIV-associated TB is a distinct, severe condition which shares many features in common with sepsis resulting from blood stream infections due to bacterial infections. Yet no treatment regimens have been specifically evaluated in this key patient population.

Is the standard treatment used in pulmonary TB adequate for treating disseminated HIV-associated TB? To answer this question, CIDRI-Africa Principal Investigator Prof. Graeme Meintjes and his team will evaluate several possible treatments.

Prof. Meintjes and his team will address the need for targeted treatment in a two-stage research programme. They will invite HIV-infected in-patients with newly diagnosed TB, who will receive standard treatment, to participate in the studies. In Stage 1 the team will evaluate 8 potential blood and urine biomarkers of M. tuberculosis load in order to develop methods for measuring the efficacy of different treatment strategies in the next stage.

In Stage 2, the best performing biomarkers will be used to assess the effects of enhanced antibiotic therapy in patients with disseminated HIV-associated TB. The team will compare three therapeutic regimens: rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) plus additional rifampicin for 28 days; or RHZE plus additional rifampicin for 28 days plus levofloxacin for the following 14 days; or RHZE alone (standard treatment).

Rifampicin is a key antibacterial drug used in standard TB treatment and the team want to examine the effect of increased doses in treatment of disseminated TB. Levofloxacin is rapidly bactericidal in TB and has excellent activity against other common bacterial pathogens to which HIV-positive people may be vulnerable.

This research programme is supported by the Wellcome Trust, under Prof. Meintjes’ newly awarded Wellcome Senior Research Fellowship. The fellowship has been awarded for five years. Graeme’s long-term aim is to test promising treatment strategies in large clinical trials, with the goal of reducing deaths in patients with HIV and disseminated TB.