BACKGROUND: South Africa has a large burden of extensively drug-resistant tuberculosis (XDR-TB); only 15% of XDR-TB patients have successful outcomes. OBJECTIVE: To describe the safety and effectiveness of bedaquiline (BDQ) in the South African BDQ Clinical Access Programme. DESIGN: An interim cohort analysis. RESULTS: Of the first 91 patients enrolled between March 2013 and July 2014 (with follow-up until August 2014), 54 (59%) were human immunodeficiency virus (HIV) infected. The median CD4 count was 239 cells/μl, and all patients were on antiretroviral therapy (ART) at initiation of BDQ; 33 had XDR-TB, 41 were pre-XDR-TB with fluoroquinolone resistance and 17 were pre-XDR-TB with resistance to an injectable. Of the 91 patients, 58 (64%) had completed 24 weeks of BDQ, 28 were still on BDQ, 3 were lost to follow-up, 1 had died and 1 had BDQ withdrawn following atrial fibrillation. Of the 63 patients with 6 months follow-up, 48 (76%) had either culture-converted or remained culture-negative after initiation of BDQ. QTcF was monitored monthly and exceeded 500 ms in three participants; this resolved in all three. CONCLUSION: Interim safety and culture conversion outcomes for patients accessing BDQ in South Africa, including HIV-infected patients on ART and patients with pre-XDR- and XDR-TB, suggest that BDQ may be both efficacious and safe.

South African patients with rifampicin-resistant tuberculosis (TB) and resistance to fluoroquinolones and/or injectable drugs (extensively drug-resistant (XDR) and preXDR-TB) were granted access to bedaquiline through a clinical access programme with strict inclusion and exclusion criteria.PreXDR-TB and XDR-TB patients were treated with 24 weeks of bedaquiline within an optimised, individualised background regimen that could include levofloxacin, linezolid and clofazimine as needed. 200 patients were enrolled: 87 (43.9%) had XDR-TB, 99 (49.3%) were female and the median age was 34 years (interquartile range (IQR) 27–42). 134 (67.0%) were living with HIV; the median CD4⁺count was 281 cells·μL⁻¹(IQR 130–467) and all were on antiretroviral therapy.16 out of 200 patients (8.0%) did not complete 6 months of bedaquiline: eight were lost to follow-up, six died, one stopped owing to side effects and one was diagnosed with drug-sensitive TB. 146 out of 200 patients (73.0%) had favourable outcomes: 139 (69.5%) were cured and seven (3.5%) completed treatment. 25 patients (12.5%) died, 20 (10.0%) were lost from treatment and nine (4.5%) had treatment failure. 22 adverse events were attributed to bedaquiline, including a QT interval corrected using the Fridericia formula (QTcF) >500 ms (n=5), QTcF increase >50 ms from baseline (n=11) and paroxysmal atrial flutter (n=1).Bedaquiline added to an optimised background regimen was associated with a high rate of successful treatment outcomes for this preXDR-TB and XDR-TB cohort.

SETTING: Khayelitsha, South Africa, a peri-urban township with high burdens of tuberculosis (TB), drug-resistant tuberculosis (DR-TB), and human immunodeficiency virus (HIV) infection. OBJECTIVE: To describe case detection and patient outcomes in a community-based DR-TB programme. DESIGN: DR-TB management was integrated into primary health care in Khayelitsha from 2007 onwards. Implementation was incremental, and included training and clinician support, counselling and home visits, tuberculous infection control, a local in-patient service, and routine monitoring. Patients received treatment rapidly through their local clinic, and were only hospitalised if clinically unwell. RESULTS: DR-TB case notification (any rifampicin resistance) increased from 28 per 100 000 population per year (2005–2007) to 55/100 000/year in 2009–2011 (72% HIV-infected). From 2008 to 2011, 754 patients received treatment (86% of those diagnosed). The median time between diagnostic sputum and treatment decreased over the years of implementation to 27 days in 2011 (P < 0.001). Treatment success was 52% in 2010, with 31% default, 13% death and 4% treatment failure. Two-year survival was 65%, with poorer survival in those with HIV (HR 2.0, 95%CI 1.4–2.8), second-line drug resistance (HR 3.3, 95%CI 2.2–4.8), and diagnosis in earlier programme years (HR 1.4, 95%CI 1.1–2.0). CONCLUSION: Community-based DR-TB management is feasible, and contributes to improved case detection, reduced treatment delay and improved survival. Treatment outcomes remain poor, highlighting the poor efficacy, tolerability and lengthy duration of current treatment.