Current treatment for XDR-TB requires the assembly of a
regimen of six drugs, including a six-month phase of treatment that includes
injectable drugs, and a further 12-18 months of treatment with five drugs. Some
of the drugs used in the treatment of MDR-TB and XDR-TB have serious side-effects, including hearing loss and kidney damage in the case of several
injectable drugs. Some drugs used in the regimen are costly and unavailable in
some countries, further complicating the assembly of an effective regimen.
Even if people gain access to XDR-TB treatment and are
able to tolerate the regimen, the cure rate is shockingly low. Follow-up of people treated for XDR-TB in South Africa between 2008 and 2012 shows
that just 11% had been cured five years after beginning treatment, whereas 73%
had died. Finding a shorter-duration regimen that is effective against XDR-TB,
with fewer serious side-effects, would greatly improve the chances of treating
the infection and stopping onward transmission.
The NIX-TB study is testing a three-drug regimen consisting
of bedaquiline (Sirturo) (the first new TB drug to be approved in 40 years),
linezolid (a cheap antibiotic), and pretomanid (PA-824), an experimental TB
drug being developed by the TB Alliance.
Francesca Conradie presented results on the first 72 people
to be treated in the study.
Participants were eligible to join the study if they had
documented XDR-TB, or were intolerant to an MDR-TB regimen and remained
culture-positive, or had failed to be cured by MDR-TB treatment and remained
culture-positive. The study excluded people with HIV who had a CD4 cell count
below 50 cells/mm3, and people with cardiac arrhythmia or severe
Of the 72 participants, 51% were HIV positive, 65% had XDR-TB, 24% had MDR-TB treatment failure and 11% were intolerant of MDR-TB
treatment. The participants were fairly evenly divided by sex (54% male) and
were predominantly black (78%).
Treatment is ongoing for some participants so participant
disposition is as follows:
- 72 people initiated treatment
- 4 people died during treatment (3 due to
disseminated TB and one due to gastrointestinal bleeding)
- 28 people are still undergoing treatment
- 40 people have completed a 6-month course of
- Of these, 31 people have completed treatment and
6 months of post-treatment follow-up.
Of the 31 who have completed post-treatment follow-up, 29 people cleared XDR-TB. One person
has been reinfected with drug-susceptible TB. Another person appears to have
suffered a relapse of XDR-TB but genome sequencing is needed to determine
whether this is a true case of relapse, or whether it is a reinfection.
Culture conversion was uniformly rapid for a population with
drug-resistant TB. All participants were culture negative within four months of
starting treatment, and 26 of the 40 people who have completed treatment were
culture negative by week 8 of treatment.
Adverse events during treatment were chiefly attributable to
linezolid, and 49 of the 60 people who have undergone treatment to date have
interrupted linezolid dosing at least once. In 14 cases the dose interruption
was due to myelosuppression, and in 28% the dose interruption was due to
Dr Conradie said that peripheral neuropathy could be managed
with gabapentine, but that it gradually diminishes after treatment is