Early Mortality among Patients with HIV-associated TB in Africa: Implications for the Time to Initiate ART
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 optimal time to initiate ART in HIV-infected
patients with tuberculosis (TB) is unknown. Although early treatment may
complicate clinical management, delayed initiation may increase mortality risk.
We determined mortality rates among patients with TB in an ART program and
examined the relationship between the time to initiation of ART and outcome.
Methods: Mortality occurring both before initiation of
ART and during the first 16 weeks of ART was prospectively studied among
patients with (n = 213) and without (n = 675) TB accessing an ART program in South Africa.
Results: The mortality rate among those with TB was
1.82-fold (95%CI 1.62 to 2.80) greater than that of patients who remained
TB-free (39.7 vs 21.7 deaths/100 person-years; p = 0.003). However, multivariate
analysis revealed that mortality in the overall cohort was not independently
associated with TB but was only associated with CD4 count <100 cells/μL (AHR = 2.85, 95%CI 1.52 to 5.34) and baseline WHO
stage 4 disease (AIDS) (AHR = 2.94, 95%CI 1.80 to 4.82). Of patients with TB
diagnosed within the program but before ART initiation (n = 73), 48 had received ART by data censorship after a median of
42 days (IQR 28 to 67) from TB diagnosis. A total of 14 deaths occurred of
which 10 (71%) were among patients waiting to commence ART and most (n = 7) were within the first 4 weeks of
anti-TB treatment. Just 4 deaths occurred after initiation of ART of which 2
were due to immune reconstitution disease. Risk of death was not associated
with baseline patient or disease characteristics but only ART status.
Conclusions: Advanced immunodeficiency accounts for the
extremely high early mortality risk among patients with TB accessing ART in
this setting. Pending the results of randomised controlled trials, these data
strongly support a policy of initiation of ART within the first month from TB
diagnosis among patients with CD4 cell counts <100 cells/μL