Timing of antiretroviral therapy for HIV-1 infection and tuberculosis.

TitleTiming of antiretroviral therapy for HIV-1 infection and tuberculosis.
Publication TypeJournal Article
Year of Publication2011
AuthorsHavlir DV, Kendall MA, Ive P, Kumwenda J, Swindells S, Qasba SS, Luetkemeyer AF, Hogg E, Rooney JF, Wu X, Hosseinipour MC, Lalloo U, Veloso VG, Some FF, Kumarasamy N, Padayatchi N, Santos BR, Reid S, Hakim J, Mohapi L, Mugyenyi P, Sanchez J, Lama JR, Pape JW, Sanchez A, Asmelash A, Moko E, Sawe F, Andersen J, Sanne I
Corporate AuthorsAIDS Clinical Trials Group Study A5221
JournalN Engl J Med
Volume365
Issue16
Pagination1482-91
Date Published2011 Oct 20
ISSN1533-4406
KeywordsAdult, AIDS-Related Opportunistic Infections, Anti-Retroviral Agents, Antitubercular Agents, CD4 Lymphocyte Count, Drug Administration Schedule, Female, HIV Infections, HIV-1, Humans, Kaplan-Meier Estimate, Male, Tuberculosis
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.).

DOI10.1056/NEJMoa1013607
Alternate JournalN. Engl. J. Med.
PubMed ID22010914
PubMed Central IDPMC3327101
Grant List1U01A1069518-01 / / PHS HHS / United States
3U01 A1069401 / / PHS HHS / United States
5 U01 A1069399-0 / / PHS HHS / United States
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P30 AI027763 / AI / NIAID NIH HHS / United States
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U01 A169414-03 / / PHS HHS / United States
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U01 AI068636-01 / AI / NIAID NIH HHS / United States
U01-A1069501 / / PHS HHS / United States
U011069476-04 / / PHS HHS / United States
U01A1068636 / / PHS HHS / United States
U01A1069432 / / PHS HHS / United States
U01A1069518 / / PHS HHS / United States