title: Immunological failure of first-line and switch to second-line antiretroviral therapy among HIV-infected persons in Tanzania: analysis of routinely collected national data.
abstract: OBJECTIVE
  Rates of first-line treatment failure and switches to second-line therapy are key indicators for national HIV programmes. We assessed immunological treatment failure defined by WHO criteria in the Tanzanian national HIV programme.
  
  
  METHODS
  We included adults initiating first-line therapy in 2004-2011 with a pre-treatment CD4 count, and ≥6-months of follow-up. We assessed subhazard ratios (SHR) for immunological treatment failure, and subsequent switch to second-line therapy, using competing risks methods to account for deaths.
  
  
  RESULTS
  Of 121 308 adults, 7% experienced immunological treatment failure, and 2% died without observed immunological treatment failure, over a median 1.7 years. The 6-year cumulative probability of immunological treatment failure was 19.0% (95% CI 18.5, 19.7) and of death, 5.1% (4.8, 5.4). Immunological treatment failure predictors included earlier year of treatment initiation (P < 0.001), initiation in lower level facilities (SHR = 2.23 [2.03, 2.45] for dispensaries vs. hospitals), being male (1.27 [1.19, 1.33]) and initiation at low or high CD4 counts (for example, 1.78 [1.65, 1.92] and 5.33 [4.65, 6.10] for <50 and ≥500 vs. 200-349 cells/mm(3) , respectively). Of 7382 participants in the time-to-switch analysis, 6% switched and 5% died before switching. Four years after immunological treatment failure, the cumulative probability of switching was 7.3% (6.6, 8.0) and of death, 6.8% (6.0, 7.6). Those who immunologically failed in dispensaries, health centres and government facilities were least likely to switch.
  
  
  CONCLUSIONS
  Immunological treatment failure rates and unmet need for second-line therapy are high in Tanzania; virological monitoring, at least for persons with immunological treatment failure, is required to minimise unnecessary switches to second-line therapy. Lower level government health facilities need more support to reduce treatment failure rates and improve second-line therapy uptake to sustain the benefits of increased coverage.
authors.affiliation: London School of Hygiene & Tropical Medicine, London, UK.|Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Vanobberghen
authors.affiliation: National AIDS Control Program, Dar es Salaam, Tanzania.
authors.forename: Bonita
authors.initials: B
authors.lastname: Kilama
authors.affiliation: London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Wringe
authors.affiliation: National AIDS Control Program, Dar es Salaam, Tanzania.
authors.forename: Angela
authors.initials: A
authors.lastname: Ramadhani
authors.affiliation: London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Basia
authors.initials: B
authors.lastname: Zaba
authors.affiliation: Ministry of Health and Social Welfare, Dar es Salaam, Tanzania.
authors.forename: Donan
authors.initials: D
authors.lastname: Mmbando
authors.affiliation: London School of Hygiene & Tropical Medicine, London, UK.|Kilimanjaro Christian Medical University College, Moshi, Tanzania.
authors.forename: Jim
authors.initials: J
authors.lastname: Todd
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D013636:Tanzania / Q000453:epidemiology; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents
keywords: Adulto; CD4 lymphocyte count; Tanzania; Tanzanie; adult; adulte; antiretroviral therapy; facteurs de risque; factores de riesgo; fallo terapéutico; numération des lymphocytes CD4; risk factors; terapia antirretroviral, conteo de linfocitos CD4; thérapie antirétrovirale; treatment failure; échec du traitement