title: Temporal association between incident tuberculosis and poor virological outcomes in a South African antiretroviral treatment service.
abstract: BACKGROUND
  The temporal relationship between incident tuberculosis (TB) and virological outcomes during antiretroviral therapy (ART) is poorly defined. This was studied in a cohort in Cape Town, South Africa.
  
  
  METHODS
  Data regarding TB diagnoses, ART regimens, and 4-monthly updated viral load (VL) and CD4 count measurements were extracted from a prospectively maintained database. Rates of virological breakthrough (VL > 1000 copies/mL) and failure (VL > 1000 copies/mL on serial measurements) following initial VL suppression were calculated. Poisson models were used to calculate incidence rate ratios (IRRs) and identify risk factors for these virological outcomes.
  
  
  RESULTS
  Incident TB was diagnosed in 391 (28.5%) of 1370 patients during a median of 5.2 years follow-up. Five hundred seventy-eight episodes of virological breakthrough and 231 episodes of virological failure occurred, giving rates of 10.0 episodes per 100 person-years and 4.0 episodes per 100 person-years, respectively. In multivariate analyses adjusted for baseline and time-updated risk factors, TB was an independent risk factor for adverse virological outcomes. These associations were strongly time dependent; the 6-month period following diagnosis of incident TB was associated with a substantially increased risk of virological breakthrough (IRR: 2.3, 95% confidence interval: 1.7 to 3.2) and failure (IRR: 2.6, 95% confidence interval: 1.6 to 4.3) compared with time without a TB diagnosis. Person-time preceding TB diagnosis or more than 6 months after a TB diagnosis was not associated with poor virological outcomes.
  
  
  CONCLUSIONS
  Incident TB during ART was strongly associated with poor virological outcomes during the 6-month period following TB diagnosis. Although underlying mechanisms remain to be defined, patients with incident TB may benefit from virological monitoring and treatment adherence support.
authors.affiliation: *Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; and †The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Ankur
authors.initials: A
authors.lastname: Gupta-Wright
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lawn
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology* / Q000276:immunology; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D003521:Cyclopropanes; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D015994:Incidence; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D019829:Nevirapine / Q000627:therapeutic use; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D018119:Stavudine / Q000627:therapeutic use; D013997:Time Factors; D014376:Tuberculosis / Q000453:epidemiology* / Q000276:immunology; D019562:Viral Load; D016903:Drug Monitoring
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine; C098320:efavirenz