Abstract
BackgroundLow haemoglobin concentrations may be predictive of incident tuberculosis (TB) and death in HIV-infected patients receiving antiretroviral therapy (ART), but data are limited and inconsistent. We examined these relationships retrospectively in a long-term South African ART cohort with multiple time-updated haemoglobin measurements.MethodsProspectively collected clinical data on patients receiving ART for up to 8 years in a community-based cohort were analysed. Time-updated haemoglobin concentrations, CD4 counts and HIV viral loads were recorded, and TB diagnoses and deaths from all causes were ascertained. Anaemia severity was classified using World Health Organization criteria. TB incidence and mortality rates were calculated and Poisson regression models were used to identify independent predictors of incident TB and mortality, respectively.ResultsDuring a median follow-up of 5.0 years (IQR, 2.5-5.8) of 1,521 patients, 476 cases of incident TB and 192 deaths occurred during 6,459 person-years (PYs) of follow-up. TB incidence rates were strongly associated with time-updated anaemia severity; those without anaemia had a rate of 4.4 (95%CI, 3.8-5.1) cases/100 PYs compared to 10.0 (95%CI, 8.3-12.1), 26.6 (95%CI, 22.5-31.7) and 87.8 (95%CI, 57.0-138.2) cases/100 PYs in those with mild, moderate and severe anaemia, respectively. Similarly, mortality rates in those with no anaemia or mild, moderate and severe time-updated anaemia were 1.1 (95%CI, 0.8-1.5), 3.5 (95%CI, 2.7-4.8), 11.8 (95%CI, 9.5-14.8) and 28.2 (95%CI, 16.5-51.5) cases/100 PYs, respectively. Moderate and severe anaemia (time-updated) during ART were the strongest independent predictors for incident TB (adjusted IRR = 3.8 [95%CI, 3.0-4.8] and 8.2 [95%CI, 5.3-12.7], respectively) and for mortality (adjusted IRR = 6.0 [95%CI, 3.9-9.2] and adjusted IRR = 8.0 [95%CI, 3.9-16.4], respectively).ConclusionsIncreasing severity of anaemia was associated with exceptionally high rates of both incident TB and mortality during long-term ART. Patients receiving ART who have moderate or severe anaemia should be prioritized for TB screening using microbiological assays and may require adjunctive clinical interventions.
Highlights
Low haemoglobin concentrations may be predictive of incident tuberculosis (TB) and death in HIV-infected patients receiving antiretroviral therapy (ART), but data are limited and inconsistent
Background antiretroviral therapy (ART) reduces tuberculosis (TB) incidence rates by approximately 70% in people living with HIV [1], high TB incidence rates continue to be observed among patients receiving ART in subSaharan Africa, especially during the initial months of treatment [2,3,4,5,6,7,8,9]
To improve clinical outcomes in ART programmes in sub-Saharan Africa, it is important to identify risk factors and/or predictive markers associated with incident TB and mortality so that effective interventions may be designed and implemented
Summary
Low haemoglobin concentrations may be predictive of incident tuberculosis (TB) and death in HIV-infected patients receiving antiretroviral therapy (ART), but data are limited and inconsistent We examined these relationships retrospectively in a long-term South African ART cohort with multiple time-updated haemoglobin measurements. We have previously demonstrated that greater degrees of anaemia severity at ART initiation are associated with a high prevalence of undiagnosed TB, as well as death during the initial months of ART [11] While it remains poorly defined, we hypothesized that time-updated haemoglobin concentrations may be associated with incident TB and/or death during long-term ART. We undertook this retrospective cohort analysis among South African patients receiving ART for up to 8 years to determine TB incidence and mortality rates stratified by time-updated anaemia severity. We sought to determine whether timeupdated anaemia severity was an independent predictor for incident TB and/or mortality even after adjustment for time-updated CD4 counts
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