Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2011 Oct 20;365(16):1482-91.
doi: 10.1056/NEJMoa1013607.

Timing of antiretroviral therapy for HIV-1 infection and tuberculosis

Diane V Havlir  1 , 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 Mohapi, Peter Mugyenyi, Jorge Sanchez, Javier R Lama, Jean W Pape, Alejandro Sanchez, Aida Asmelash, Evans Moko, Fred Sawe, Janet Andersen, Ian Sanne; AIDS Clinical Trials Group Study A5221
Collaborators, Affiliations
Randomized Controlled Trial

Timing of antiretroviral therapy for HIV-1 infection and tuberculosis

Diane V Havlir et al. N Engl J Med. .

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 log(10) 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.).

PubMed Disclaimer

Figures

Figure 1
Figure 1. Enrollment and Follow-up of Study Subjects
The disposition of the subjects from screening tuberculosis suspects to study completion is shown.
Figure 2
Figure 2. Time to New AIDS Defining Illness or Death
Shown are the times to the primary endpoint of AIDS defining illness or death for the entire study population (Panel A) and for the study population by CD4+ lymphocyte stratum (Panel B).
Figure 2
Figure 2. Time to New AIDS Defining Illness or Death
Shown are the times to the primary endpoint of AIDS defining illness or death for the entire study population (Panel A) and for the study population by CD4+ lymphocyte stratum (Panel B).
See this image and copyright information in PMC

Comment in

References

    1. Sterling TR, Pham PA, Chaisson RE. HIV infection-related tuberculosis: clinical manifestations and treatment. Clin Infect Dis. 2010;50 Suppl 3:S223–S230. - PubMed
    1. Abdool Karim SS, Naidoo K, Grobler A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010;362(8):697–706. - PMC - PubMed
    1. Breen RA, Smith CJ, Bettinson H, et al. Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection. Thorax. 2004;59(8):704–707. - PMC - PubMed
    1. Burman W, Weis S, Vernon A, et al. Frequency, severity and duration of immune reconstitution events in HIV-related tuberculosis. Int J Tuberc Lung Dis. 2007;11(12):1282–1289. - PubMed
    1. Global Tuberculosis Control: A short update to the 2009 report. 2009 (Accessed at http://whqlibdoc.who.int/publications/2009/9789241598866_eng.pdf)

Publication types

Substances

Associated data