Timing of antiretroviral therapy for HIV-1 infection and tuberculosis

Diane V. Havlir, Michelle A. Kendall, Prudence Ive, Johnstone Kumwenda, Susan Swindells, Sarojini S. Qasba, Anne F. Luetkemeyer, Evelyn Hogg, James F. Rooney, Xingye Wu, Mina C. Hosseinipour, Umesh Lalloo, Valdilea G. Veloso, Fatuma F. Some, N. Kumarasamy, Nesri Padayatchi, Breno R. Santos, Stewart Reid, James Hakim, Lerato MohapiPeter Mugyenyi, Jorge Sanchez, Javier R. Lama, Jean W. Pape, Alejandro Sanchez, Aida Asmelash, Evans Moko, Fred Sawe, Janet Andersen, Ian Sanne

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415 Scopus citations

Abstract

BACKGROUND: Antiretroviral therapy (ART) is indicated during tuberculosis treatment in patients infected with human immunodeficiency virus type 1 (HIV-1), but the timing for the initiation of ART when tuberculosis is diagnosed in patients with various levels of immune compromise is not known. METHODS: We conducted an open-label, randomized study comparing earlier ART (within 2 weeks after the initiation of treatment for tuberculosis) with later ART (between 8 and 12 weeks after the initiation of treatment for tuberculosis) in HIV-1 infected patients with CD4+ T-cell counts of less than 250 per cubic millimeter and suspected tuberculosis. The primary end point was the proportion of patients who survived and did not have a new (previously undiagnosed) acquired immunodeficiency syndrome (AIDS)-defining illness at 48 weeks. RESULTS: A total of 809 patients with a median baseline CD4+ T-cell count of 77 per cubic millimeter and an HIV-1 RNA level of 5.43 log10 copies per milliliter were enrolled. In the earlier-ART group, 12.9% of patients had a new AIDS-defining illness or died by 48 weeks, as compared with 16.1% in the later-ART group (95% confidence interval [CI], -1.8 to 8.1; P = 0.45). Among patients with screening CD4+ T-cell counts of less than 50 per cubic millimeter, 15.5% of patients in the earlier-ART group versus 26.6% in the later-ART group had a new AIDS-defining illness or died (95% CI, 1.5 to 20.5; P = 0.02). Tuberculosis-associated immune reconstitution inflammatory syndrome was more common with earlier ART than with later ART (11% vs. 5%, P = 0.002). The rate of viral suppression at 48 weeks was 74% and did not differ between the groups (P = 0.38). CONCLUSIONS: Overall, earlier ART did not reduce the rate of new AIDS-defining illness and death, as compared with later ART. In persons with CD4+ T-cell counts of less than 50 per cubic millimeter, earlier ART was associated with a lower rate of new AIDS-defining illnesses and death. (Funded by the National Institutes of Health and others; ACTG A5221 ClinicalTrials.gov number, NCT00108862.)

Original languageEnglish (US)
Pages (from-to)1482-1491
Number of pages10
JournalNew England Journal of Medicine
Volume365
Issue number16
DOIs
StatePublished - Oct 20 2011

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ASJC Scopus subject areas

  • Medicine(all)

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Havlir, D. V., Kendall, M. A., Ive, P., Kumwenda, J., Swindells, S., Qasba, S. S., Luetkemeyer, A. F., Hogg, E., Rooney, J. F., Wu, X., Hosseinipour, M. C., Lalloo, U., Veloso, V. G., Some, F. F., Kumarasamy, N., Padayatchi, N., Santos, B. R., Reid, S., Hakim, J., ... Sanne, I. (2011). Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. New England Journal of Medicine, 365(16), 1482-1491. https://doi.org/10.1056/NEJMoa1013607