TB-associated Immune Reconstitution Disease: Incidence, Risk Factors, and Effect within an ART Program in Sub-Saharan Africa
Stephen Lawn*1,2, Stephen Lawn*1,2, L Myer3,4, L Myer3,4, L G Bekker1, and R Wood1
1Desmond Tutu HIV Ctr, Faculty of Hlth Sci, Univ of Cape Town, South Africa; 2London Sch of Hygiene and Tropical Med, UK; 3Sch of Publ Hlth and Family Med, Faculty of Hlth Sci, Univ of Cape Town, South Africa; and 4Columbia Univ Mailman Sch of Publ Hlth, New York, NY, US
Background: The prevalence of active tuberculosis (TB) is
high among patients accessing ART programs in Sub-Saharan Africa. Such patients
are at risk of developing TB-associated immune reconstitution disease (IRD)
after initiation of ART. However, the frequency, risk factors, and effect of
TB-associated IRD in such programs are not known.
Methods: A retrospective analysis of detailed data from a
study cohort enrolled over 3 years within a community-based ART service in South Africa.
Patients receiving treatment for TB at the time ART was initiated (n = 160) were studied. Cases of
TB-associated IRD during the first 4 months ART were ascertained.
Results: The median baseline CD4 cell count was 68 cells/μL (IQR 29 to 133).
ART was initiated after a median of 105 days (IQR 61 to 164) from TB diagnosis,
many patients having already completed part of their treatment course for TB
prior to entering the ART programme. Overall, IRD was diagnosed in 12% of
patients (n = 19). However, IRD
developed in 32% (n = 12) of those
who started ART with 2 months of TB diagnosis. Pulmonary involvement was
observed among 84% (n = 16) and
intra-abdominal manifestations were also common (37%). In multivariate
analysis, risk of IRD was strongly associated with early ART initiation and low
baseline CD4 cell count. Of patients with CD4 counts <50 cells/μL, the
proportions who developed IRD following initiation of ART within 0 to 30, 31 to
60, 61 to 90, 91 to 120, and >120 days of TB diagnosis were 100%, 33%, 14%,
7%, and 0%, respectively. Overall, 4% (n = 7) of the cohort required secondary level health-care for IRD
and 2 (1%) patients died.
The risk of TB-associated IRD in this
setting is very high for those with low baseline CD4 cell counts initiating ART
early in the course of antituberculosis treatment. However, most cases were
self-limiting; overall secondary health-care utilisation and mortality risk
from IRD were low.