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Background: Approximately 30% of TB/HIV patients die within 12 months of starting TB treatment. Current treatment strategies to reduce TB/HIV mortality rely largely on the optimal management of HIV disease. But, as supported by autopsy studies, the problem might also be seen from the TB perspective: more intensive TB treatment might also reduce mortality.
Methods: We conducted an open label, 3 parallel arms, randomised controlled trial, among TB/HIV co-infected patients who were ARV-naive and with a CD4 cell-count ≥50 cells/mm3 at enrolment, in Benin, Guinea and Senegal. The trial arms were: Arm A - ARV initiation at 2 weeks combined with standard TB treatment; Arm B (control arm) - ARV initiation at 8 weeks combined with standard TB treatment; Arm C - ARV initiation at 8 weeks with high-dose rifampicin (15mg/kg) during the first 2 months of TB treatment. The primary outcome was 12-month mortality.
Results: In total, 778 TB/HIV patients were randomised (n=262, 258 and 258 for arms A, B and C respectively). All TB cases were bacteriologically confirmed. CD4 cell-counts ranged from 50-949 (median 183), balanced across arms. By January 2016, all patients completed 12 months of follow-up post-randomisation. The overall 12-month mortality rates were: 11.8, 15.5 and 10.9 per 100 person-years in arms A, B and C respectively. Using Cox regression, there was no evidence that overall mortality rates differed by treatment arm (p=0.40). Restricting the analysis to patients with a baseline CD4 cell-count < 100 cells/mm3, mortality was substantially reduced (p=0.006) in Arm C, with high-dose rifampicin, compared with Arm B, but not in Arm A (p=0.24) (Fig 1). There was no evidence of an increased risk of hepatotoxicity in Arm C.

Fig 1: Time to mortality, from randomisation date in patients with less 100 CD4 count and more than 100 CD4 count? Kaplan-Meier analyses
[Fig 1: Time to mortality, from randomisation date in patients with less 100 CD4 count and more than 100 CD4 count? Kaplan-Meier analyses]


Conclusions: More aggressive TB treatment using high dose of rifampicin, in addition to ARV treatment, could reduce TB/HIV mortality among severely immunosuppressed co-infected TB/HIV patients.