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Time to Initiate Antiretroviral Therapy Between 4 Weeks and 12 Weeks of Tuberculosis Treatment in HIV-Infected Patients: Results From the TIME Study

Manosuthi, Weerawat MD; Mankatitham, Wiroj MD; Lueangniyomkul, Aroon MD; Thongyen, Supeda MPH; Likanonsakul, Sirirat MSc; Suwanvattana, Pawita MSc; Thawornwan, Unchana MSc; Suntisuklappon, Busakorn BSc; Nilkamhang, Samruay BC; Sungkanuparph, Somnuek MDfor the TIME Study Team

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 1st, 2012 - Volume 60 - Issue 4 - p 377–383
doi: 10.1097/QAI.0b013e31825b5e06
Clinical Science

Background: Optimal timing for initiation of antiretroviral therapy (ART) among HIV-infected patients with tuberculosis (TB) is not well established.

Methods: HIV/TB-coinfected patients were randomized to initiate tenofovir/lamivudine/efavirenz at 4 weeks (4-week group) or 12 weeks (12-week group) of TB treatment. The primary outcome was 1-year all-cause mortality.

Results: Of 156 patients, 79 were in 4-week group and 77 in 12-week group. Overall, median (interquartile range) CD4 was 43 (47–106) cells per cubic millimeter and median (interquartile range) HIV-1 RNA was 5.8 (5.4–6.3) log copies per milliliter. Eleven (7%) mortalities occurred in a total follow-up period of 137 patient-years. Seven percent (6/79, 8.76 per 100 patient-years) mortalities were in 4-week group, and 6% (5/77, 7.25 per 100 person-years) mortalities were in 12-week group [relative risk (RR) = 0.845, 95% confidence interval (CI) = 0.247 to 2.893]. Twenty-eight (35%) patients in 4-week group and 25 (32%) patients in 12-week group were hospitalized (RR = 1.142, 95% CI = 0.588 to 2.217). Grade 2–4 adverse events were 39% (31/79) in 4-week group and 34% (26/77) in 12-week group (RR = 1.267, 95% CI = 0.659 to 2.435). In multivariate analysis, “low albumin” (RR = 2.695, 95% CI = 1.353 to 5.475) and “low baseline CD4 count” (RR = 4.878, 95% CI = 1.019 to 23.256) were the independent predictors of mortality. Immune reconstitution inflammatory syndrome was more frequent in 4-week group with an incidence of 8.86 versus 5.02 per 100 person-months in 12-week group over the first 6 months of ART (P = 0.069).

Conclusions: In middle-income countries where ART is initiated at CD4 count of <350 cells per cubic millimeter, immediate initiation of ART in HIV-infected patients with active TB was not associated with survival advantage when compared to initiation of ART at 12 weeks.

*Department of Medicine, Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand

Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Correspondence to: Weerawat Manosuthi, MD, Department of Medicine, Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Tiwanon Road, Nonthaburi 11000, Thailand (e-mail:

Supported by a research grant from The Thailand Research Fund and the Department of Disease Control, Ministry of Public Health, Thailand.

The authors have no conflicts of interest to disclose.

Received January 20, 2012

Accepted April 19, 2012

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.