Timing of antiretroviral therapy for HIV-1 infection and tuberculosis.
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.).
University of California, San Francisco, 995 Potrero Ave., Bldg. 80, Ward 84, San Francisco, CA 94110-2897, USA. dhavlir@php.ucsf.edu
Diane V
DV
Havlir
Michelle A
MA
Kendall
Prudence
P
Ive
Johnstone
J
Kumwenda
Susan
S
Swindells
Sarojini S
SS
Qasba
Anne F
AF
Luetkemeyer
Evelyn
E
Hogg
James F
JF
Rooney
Xingye
X
Wu
Mina C
MC
Hosseinipour
Umesh
U
Lalloo
Valdilea G
VG
Veloso
Fatuma F
FF
Some
N
N
Kumarasamy
Nesri
N
Padayatchi
Breno R
BR
Santos
Stewart
S
Reid
James
J
Hakim
Lerato
L
Mohapi
Peter
P
Mugyenyi
Jorge
J
Sanchez
Javier R
JR
Lama
Jean W
JW
Pape
Alejandro
A
Sanchez
Aida
A
Asmelash
Evans
E
Moko
Fred
F
Sawe
Janet
J
Andersen
Ian
I
Sanne
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000995:Antitubercular Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015497:HIV-1; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*
D044966:Anti-Retroviral Agents; D000995:Antitubercular Agents