Temporal association between incident tuberculosis and poor virological outcomes in a South African antiretroviral treatment service

Abstract

Introduction: The temporal relationship between incident tuberculosis (TB) and virological outcomes during antiretroviral therapy (ART) is poorly defined. This was studied in a cohort in Cape Town, South Africa.

Methods: Data regarding TB diagnoses, ART regimens, and 4-monthly updated viral load (VL) and CD4 count measurements were extracted from a prospectively maintained database. Rates of virological breakthrough (VL > 1000 copies/mL) and failure (VL > 1000 copies/mL on serial measurements) following initial VL suppression were calculated. Poisson models were used to calculate incidence rate ratios (IRRs) and identify risk factors for these virological outcomes.

Results: Incident TB was diagnosed in 391 (28.5%) of 1370 patients during a median of 5.2 years follow-up. Five hundred seventy-eight episodes of virological breakthrough and 231 episodes of virological failure occurred, giving rates of 10.0 episodes per 100 person-years and 4.0 episodes per 100 person-years, respectively. In multivariate analyses adjusted for baseline and time-updated risk factors, TB was an independent risk factor for adverse virological outcomes. These associations were strongly time dependent; the 6-month period following diagnosis of incident TB was associated with a substantially increased risk of virological breakthrough (IRR: 2.3, 95% confidence interval: 1.7 to 3.2) and failure (IRR: 2.6, 95% confidence interval: 1.6 to 4.3) compared with time without a TB diagnosis. Person-time preceding TB diagnosis or more than 6 months after a TB diagnosis was not associated with poor virological outcomes.

Conclusions: Incident TB during ART was strongly associated with poor virological outcomes during the 6-month period following TB diagnosis. Although underlying mechanisms remain to be defined, patients with incident TB may benefit from virological monitoring and treatment adherence support.

FIGURE 1

Patient enrollment and outcomes during follow-up.

FIGURE 2

Unadjusted association between virological breakthrough rates (95% CI), virological failure rates (95% CI), and time-updated CD4 cell counts.

FIGURE 3

Virological breakthrough () and virological failure () IRR associated with person-time accrued following a diagnosis of incident TB, 6-month period before TB, 6-month period after TB diagnosis, and time > 6 months after TB diagnosis, compared with person-time with no incident TB diagnosis.