Severe adverse events during second-line TB treatment in the context of high HIV co-infection in South Africa: a retrospective cohort study
Abstract
Background
According to the World
Health Organization, South Africa ranks as one of the highest
burden of TB, TB/HIV co-infection, and drug-resistant TB (DR-TB)
countries. DR-TB treatment is complicated to administer and
relies on the use of multiple toxic drugs, with potential for
severe adverse drug reactions. We report the occurrence of
adverse events (AEs) during a standardised DR-TB treatment
regimen at two outpatient, decentralized, public-sector sites in
Johannesburg, South Africa.
Methods
We reviewed medical records
of the six-month intensive treatment phase for
rifampicin-resistant (RR) TB patients registered May 2012 -
December 2014. Patients contributed follow-up time until death,
loss from treatment, censoring (6 months) or data extraction. A
standardized regimen of kanamycin, moxifloxacin, ethionamide,
terizidone, and pyrazinamide was used according to national
guidelines. AEs were graded using the AIDS Clinical Trial Group
scale. We present subhazard ratios from competing risk analysis
for time to severe AE, accounting for mortality and loss from
treatment.
Results
Across the two sites, 578
eligible patient files were reviewed. 36.7 % were categorized as
low weight (≤50 kg) at DR-TB initiation. 76.0 % had no
history of TB treatment prior to the current episode of RR TB.
26.8 % were diagnosed with RR TB while hospitalized, indicating
poor clinical condition. 82.5 % of patients were also HIV
positive, of whom 43.8 % were on ART prior to RR TB treatment
and 32.1 % initiated ART with or after RR TB treatment. Median
CD4 count was 114.5 (IQR: 45-246.5). Overall, 578 reports of AEs
were captured for 204 patients (35.3 %) and 110 patients (19.0
%) had at least one severe AE reported. Patients with at least
one AE experienced a median of 3 (IQR: 2-4) AEs per patient.
HIV-positive patients with CD4 counts ≤100 cells/mm3 and
those newly initiating ART were more likely to experience a
severe AE (sHR: 2.76, 95 % CI: 1.30–5.84 and sHR: 3.07, 95
% CI: 1.46–6.46, respectively).
Conclusion
Severe AE are common
during the first 6 months of RR TB treatment and HIV-positive
patients newly initiating ART have the highest subdistribution
hazard ratio for severe AE, accounting for the competing risks
of death and loss from treatment.
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Source:
BMC Infectious Diseases
