Time to ART Initiation among Patients Treated for Rifampicin-Resistant Tuberculosis in Khayelitsha, South Africa: Impact on Mortality and Treatment Success.

Johnny Flippie Daniels,Erika Mohr,Jennifer Hughes,Mary Edginton,Helen Suzanne Cox,Gilles Van Cutsem,Sizulu Moyo,Sven Gudmund Hinderaker,Graeme Meintjes,Mohammed Khogali,Vivian Cox,Virginia De Azevedo,Pierre Roques

doi:10.1371/journal.pone.0142873

Abstract

SettingKhayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection.ObjectiveTo describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes.DesignA retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation.ResultsOf the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm3. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2–8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2–8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1–18.1), CD4 count ≤100 (aHR 2.1, CI 1.0–4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1–5.4).ConclusionsDespite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.

Highlights

The emergence of rifampicin-resistant tuberculosis (RR-TB) challenges the success of national TB control programs and the survival of patients with the disease [1]
Of the 696 RR-TB and human immunodeficiency virus (HIV)-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on antiretroviral therapy (ART) when RR-TB treatment was initiated
Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2–8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57)

Summary

Results

Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2–8 weeks and 72 (24%) after 8 weeks. Time to ART after RR-TB Treatment Initiation within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2–8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1–18.1), CD4 count 100 (aHR 2.1, CI 1.0–4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1–5.4)

Conclusions

Background

Ethical approval

Discussion