CD4 Deficit and Tuberculosis Risk Persist With Delayed Antiretroviral Therapy: 5-Year Data From CIPRA HT-001
International Journal of Tuberculosis and Lung Disease
SETTING: Port-au-Prince, Haiti. OBJECTIVE: To determine long-term effects of early vs. delayed initiation of antiretroviral therapy (ART) on immune recovery and tuberculosis (TB) risk in human immunodeficiency virus (HIV) infected individuals. DESIGN: Open-label randomized controlled trial of immediate ART in HIV-infected adults with CD4 counts between 200 and 350 cells/mm(3) vs. deferring ART until the CD4 count was <200 cells/mm(3). The primary comparisons were CD4 counts over time and risk for incident TB, with 5 years of follow-up. RESULTS: A total of 816 participants were enrolled, with 408 in each treatment arm. The early treatment group started ART within 2 weeks, while the deferred treatment group started ART a median of 1.3 years after enrollment. After 5 years, the mean CD4 count in the early treatment group was significantly higher than in the deferred treatment group (496 cells/mm(3), 95% confidence interval [CI] 477-515 vs. 373 cells/mm(3), 95%CI 357-389; P < 0.0001). TB risk was higher in the deferred treatment group (unadjusted HR 2.41, 95%CI 1.56-3.74; P < 0.0001) and strongly correlated with lower CD4 counts in time-dependent multivariate analysis. CONCLUSION: Delays in ART initiation for HIV-infected adults with CD4 counts of 200-350 cells/mm(3) can result in long-term immune dysfunction and persistent increased risk for TB. TRIAL REGISTRATION: ClinicalTrials.gov NCT00120510.
Collins, S. E.; Juste, M.A. Jean; Koenig, S. P.; Secours, R.; Ocheretina, O.; Bernard, D.; Riviere, C.; Calnan, M.; Dunning, A.; Hurtado Rua, Sandra M.; Johnson, W. D. Jr.; Pape, J. W.; Fitzgerald, D. W.; and Severe, P., "CD4 Deficit and Tuberculosis Risk Persist With Delayed Antiretroviral Therapy: 5-Year Data From CIPRA HT-001" (2015). Mathematics Faculty Publications. 169.
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This work was supported by grants from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (grant numbers AI098627, AI58257) and from the Fogarty International Center at the National Institutes of Health, Bethesda, MD, USA (grant numbers TW00018, TW009337).