title: Evaluation of the impact of immediate versus WHO recommendations-guided antiretroviral therapy initiation on HIV incidence: the ANRS 12249 TasP (Treatment as Prevention) trial in Hlabisa sub-district, KwaZulu-Natal, South Africa: study protocol for a cluster randomised controlled trial.
abstract: BACKGROUND
  Antiretroviral therapy (ART) suppresses HIV viral load in all body compartments and so limits the risk of HIV transmission. It has been suggested that ART not only contributes to preventing transmission at individual but potentially also at population level. This trial aims to evaluate the effect of ART initiated immediately after identification/diagnosis of HIV-infected individuals, regardless of CD4 count, on HIV incidence in the surrounding population. The primary outcome of the overall trial will be HIV incidence over two years. Secondary outcomes will include i) socio-behavioural outcomes (acceptability of repeat HIV counselling and testing, treatment acceptance and linkage to care, sexual partnerships and quality of life); ii) clinical outcomes (mortality and morbidity, retention into care, adherence to ART, virologic failure and acquired HIV drug resistance), iii) cost-effectiveness of the intervention. The first phase will specifically focus on the trial's secondary outcomes.
  
  
  METHODS
  A cluster-randomised trial in 34 (2 × 17) clusters within a rural area of northern KwaZulu-Natal (South Africa), covering a total population of 34,000 inhabitants aged 16 years and above, of whom an estimated 27,200 would be HIV-uninfected at start of the trial. The first phase of the trial will include ten (2 × 5) clusters. Consecutive rounds of home-based HIV testing will be carried out. HIV-infected participants will be followed in dedicated trial clinics: in intervention clusters, they will be offered immediate ART initiation regardless of CD4 count and clinical stage; in control clusters they will be offered ART according to national treatment eligibility guidelines (CD4 <350 cells/μL, World Health Organisation stage 3 or 4 disease or multidrug-resistant/extensively drug-resistant tuberculosis). Following proof of acceptability and feasibility from the first phase, the trial will be rolled out to further clusters.
  
  
  CONCLUSIONS
  We aim to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level. Data collected from the participants at home and in the clinics will inform understanding of socio-behavioural, economic and clinical impacts of the intervention as well as feasibility and generalizability.
  
  
  BACKGROUND
  Clinicaltrials.gov: NCT01509508; South African Trial Register: DOH-27-0512-3974.
authors.affiliation: Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, KwaZulu-Natal, South Africa. ciwuji@africacentre.ac.za
authors.forename: Collins C
authors.initials: CC
authors.lastname: Iwuji
authors.forename: Joanna
authors.initials: J
authors.lastname: Orne-Gliemann
authors.forename: Frank
authors.initials: F
authors.lastname: Tanser
authors.forename: Sylvie
authors.initials: S
authors.lastname: Boyer
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lessells
authors.forename: France
authors.initials: F
authors.lastname: Lert
authors.forename: John
authors.initials: J
authors.lastname: Imrie
authors.forename: Till
authors.initials: T
authors.lastname: Bärnighausen
authors.forename: Claire
authors.initials: C
authors.lastname: Rekacewicz
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bazin
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Newell
authors.forename: François
authors.initials: F
authors.lastname: Dabis
mesh_terms: D000293:Adolescent; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D018791:CD4 Lymphocyte Count; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D004334:Drug Administration Schedule; D016527:Drug Costs; D024882:Drug Resistance, Viral; D005240:Feasibility Studies; D019983:Guideline Adherence; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000401:mortality / Q000635:transmission / Q000821:virology; D007722:Health Knowledge, Attitudes, Practice; D006801:Humans; D015994:Incidence; D055118:Medication Adherence; D017410:Practice Guidelines as Topic; D011237:Predictive Value of Tests; D011788:Quality of Life; D012107:Research Design; D019035:Rural Health Services; D012725:Sexual Behavior; D013019:South Africa / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D014944:World Health Organization; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents