N Engl J Med. 2011 Oct 20;365(16):1482-91. doi: 10.1056/NEJMoa1013607.

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

Source

University of California, San Francisco, 995 Potrero Ave., Bldg. 80, Ward 84, San Francisco, CA 94110-2897, USA. dhavlir@php.ucsf.edu

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.).

Comment in

Timing of antiretroviral therapy for HIV-1-associated tuberculosis. [N Engl J Med. 2012]
Timing of antiretroviral therapy for HIV-1-associated tuberculosis.Lawn SD, Wood R. N Engl J Med. 2012 Feb 2; 366(5):474; author reply 475-6.
When to start antiretroviral therapy in HIV-associated tuberculosis. [N Engl J Med. 2011]
When to start antiretroviral therapy in HIV-associated tuberculosis.Török ME, Farrar JJ. N Engl J Med. 2011 Oct 20; 365(16):1538-40.