title: Partner-based adherence intervention for second-line antiretroviral therapy (ACTG A5234): a multinational randomised trial.
abstract: Adherence is key to the success of antiretroviral therapy. Enhanced partner support might benefit patients with previous treatment failure. We aimed to assess whether an enhanced partner-based support intervention with modified directly observed therapy would improve outcomes with second-line therapy in HIV-infected patients for whom first-line therapy had failed.
  
  
  
  We did a multicentre, international, randomised clinical trial at nine sites in Botswana, Brazil, Haiti, Peru, South Africa, Uganda, Zambia, and Zimbabwe. Participants aged 18 years or older for whom first-line therapy had failed, with HIV RNA concentrations greater than 1000 copies per mL and with a willing partner, were randomly assigned (1:1), via computer-generated randomisation, to receive partner-based modified directly observed therapy or standard of care. Randomisation was stratified by screening HIV RNA concentration (≤10 000 copies per mL vs >10 000 copies per mL). Participants and site investigators were not masked to group assignment. Primary outcome was confirmed virological failure (viral load >400 copies per mL) by week 48. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00608569.
  
  
  
  Between April 23, 2009, and Sept 29, 2011, we randomly assigned 259 participants to the modified directly observed therapy group (n=129) or the standard-of-care group (n=130). 34 (26%) participants in the modified directly observed therapy group achieved the primary endpoint of virological failure by week 48 compared with 23 (18%) participants in the standard-of-care group. The Kaplan-Meier estimated cumulative probability of virological failure by week 48 was 25·1% (95% CI 17·7-32·4) in the modified directly observed therapy group and 17·3% (10·8-23·7) in the standard-of-care group, for a weighted difference in standard of care versus modified directly observed therapy of -6·6% (95% CI -16·5% to 3·2%; p=0·19). 36 (14%) participants reported at least one grade 3 or higher adverse event or laboratory abnormality (n=21 in the modified directly observed therapy group and n=15 in the standard-of-care group).
  
  
  
  Partner-based training with modified directly observed therapy had no effect on virological suppression. The intervention does not therefore seem to be a promising strategy to increase adherence. Intensive follow-up with clinic staff might be a viable approach in this setting.
  
  
  
  AIDS Clinical Trials Group and the National Institute of Allergy and Infectious Diseases, US National Institutes of Health.
authors.affiliation: University of Pennsylvania Perelman School of Medicine, Medicine (Infectious Diseases) and Epidemiology, Philadelphia, PA, USA. Electronic address: grossr@mail.med.upenn.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Gross
authors.affiliation: Harvard School of Public Health, Biostatistics, Boston, MA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Asociacion Civil IMPACTA Salud y Educacion, Lima, Peru.
authors.forename: Alberto
authors.initials: A
authors.lastname: La Rosa
authors.affiliation: Harvard School of Public Health, Biostatistics, Boston, MA, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Harvard School of Public Health, Biostatistics, Boston, MA, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Rosenkranz
authors.affiliation: FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Sandra Wagner
authors.initials: SW
authors.lastname: Cardoso
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: Francis
authors.initials: F
authors.lastname: Ssali
authors.affiliation: EUPATI, Barcelona, Spain.
authors.forename: Rob
authors.initials: R
authors.lastname: Camp
authors.affiliation: National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Godfrey
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Cohn
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Robbins
authors.affiliation: University of Zimbabwe, Harare, Zimbabwe.
authors.forename: Anthony
authors.initials: A
authors.lastname: Chisada
authors.affiliation: Lancet Laboratories, Johannesburg, South Africa.
authors.forename: Carole L
authors.initials: CL
authors.lastname: Wallis
authors.affiliation: Yale University School of Nursing, New Haven, CT USA.
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Reynolds
authors.affiliation: Harvard School of Public Health, Biostatistics, Boston, MA, USA.
authors.forename: Darlene
authors.initials: D
authors.lastname: Lu
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Safren
authors.affiliation: Social and Scientific Systems, Silver Spring, MD, USA.
authors.forename: Lara
authors.initials: L
authors.lastname: Hosey
authors.affiliation: GHESKIO, Port au Prince, Haiti.
authors.forename: Patrice
authors.initials: P
authors.lastname: Severe
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001071:Appointments and Schedules; D001902:Botswana; D001938:Brazil; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006205:Haiti; D006801:Humans; D008297:Male; D055118:Medication Adherence / Q000523:psychology*; D008875:Middle Aged; D010568:Peru; D012108:Research Personnel; D013019:South Africa; D059039:Standard of Care; D017211:Treatment Failure; D014454:Uganda; D014481:United States; D019562:Viral Load / Q000187:drug effects; D015030:Zimbabwe
chemical_list: D019380:Anti-HIV Agents