title: Time to initiate antiretroviral therapy between 4 weeks and 12 weeks of tuberculosis treatment in HIV-infected patients: results from the TIME study.
abstract: 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.
authors.affiliation: Department of Medicine, Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand. drweerawat@hotmail.com
authors.forename: Weerawat
authors.initials: W
authors.lastname: Manosuthi
authors.forename: Wiroj
authors.initials: W
authors.lastname: Mankatitham
authors.forename: Aroon
authors.initials: A
authors.lastname: Lueangniyomkul
authors.forename: Supeda
authors.initials: S
authors.lastname: Thongyen
authors.forename: Sirirat
authors.initials: S
authors.lastname: Likanonsakul
authors.forename: Pawita
authors.initials: P
authors.lastname: Suwanvattana
authors.forename: Unchana
authors.initials: U
authors.lastname: Thawornwan
authors.forename: Busakorn
authors.initials: B
authors.lastname: Suntisuklappon
authors.forename: Samruay
authors.initials: S
authors.lastname: Nilkamhang
authors.forename: Somnuek
authors.initials: S
authors.lastname: Sungkanuparph
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000995:Antitubercular Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D060085:Coinfection / Q000188:drug therapy / Q000401:mortality; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy* / Q000401:mortality; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents