title: Cryptococcal meningitis screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: an open-label, randomised controlled trial.
abstract: BACKGROUND
  Mortality in people in Africa with HIV infection starting antiretroviral therapy (ART) is high, particularly in those with advanced disease. We assessed the effect of a short period of community support to supplement clinic-based services combined with serum cryptococcal antigen screening.
  
  
  METHODS
  We did an open-label, randomised controlled trial in six urban clinics in Dar es Salaam, Tanzania, and Lusaka, Zambia. From February, 2012, we enrolled eligible individuals with HIV infection (age ≥18 years, CD4 count of <200 cells per μL, ART naive) and randomly assigned them to either the standard clinic-based care supplemented with community support or standard clinic-based care alone, stratified by country and clinic, in permuted block sizes of ten. Clinic plus community support consisted of screening for serum cryptococcal antigen combined with antifungal therapy for patients testing antigen positive, weekly home visits for the first 4 weeks on ART by lay workers to provide support, and in Tanzania alone, re-screening for tuberculosis at 6-8 weeks after ART initiation. The primary endpoint was all-cause mortality at 12 months, analysed by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number registry, number ISCRTN 20410413.
  
  
  RESULTS
  Between Feb 9, 2012, and Sept 30, 2013, 1001 patients were randomly assigned to clinic plus community support and 998 to standard care. 89 (9%) of 1001 participants in the clinic plus community support group did not receive their assigned intervention, and 11 (1%) of 998 participants in the standard care group received a home visit or a cryptococcal antigen screen rather than only standard care. At 12 months, 25 (2%) of 1001 participants in the clinic plus community support group and 24 (2%) of 998 participants in the standard care group had been lost to follow-up, and were censored at their last visit for the primary analysis. At 12 months, 134 (13%) of 1001 participants in the clinic plus community support group had died compared with 180 (18%) of 998 in the standard care group. Mortality was 28% (95% CI 10-43) lower in the clinic plus community support group than in standard care group (p=0·004).
  
  
  CONCLUSIONS
  Screening and pre-emptive treatment for cryptococcal infection combined with a short initial period of adherence support after initiation of ART could substantially reduce mortality in HIV programmes in Africa.
  
  
  BACKGROUND
  European and Developing Countries Clinical Trials Partnership.
authors.affiliation: National Institute for Medical Research, Muhimbili Medical Research Centre, Dar es Salaam, Tanzania.
authors.forename: Sayoki
authors.initials: S
authors.lastname: Mfinanga
authors.affiliation: Institute for Medical Research and Training, University Teaching Hospital, Lusaka, Zambia.
authors.forename: Duncan
authors.initials: D
authors.lastname: Chanda
authors.affiliation: National Institute for Medical Research, Muhimbili Medical Research Centre, Dar es Salaam, Tanzania.
authors.forename: Sokoine L
authors.initials: SL
authors.lastname: Kivuyo
authors.affiliation: Faculty of Public Health Policy, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Lorna
authors.initials: L
authors.lastname: Guinness
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Bottomley
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Simms
authors.affiliation: Institute for Medical Research and Training, University Teaching Hospital, Lusaka, Zambia.
authors.forename: Carol
authors.initials: C
authors.lastname: Chijoka
authors.affiliation: National Institute for Medical Research, Muhimbili Medical Research Centre, Dar es Salaam, Tanzania.
authors.forename: Ayubu
authors.initials: A
authors.lastname: Masasi
authors.affiliation: National Institute for Medical Research, Muhimbili Medical Research Centre, Dar es Salaam, Tanzania.
authors.forename: Godfather
authors.initials: G
authors.lastname: Kimaro
authors.affiliation: National Institute for Medical Research, Muhimbili Medical Research Centre, Dar es Salaam, Tanzania.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ngowi
authors.affiliation: National Institute for Medical Research, Muhimbili Medical Research Centre, Dar es Salaam, Tanzania.
authors.forename: Amos
authors.initials: A
authors.lastname: Kahwa
authors.affiliation: Institute for Medical Research and Training, University Teaching Hospital, Lusaka, Zambia.
authors.forename: Peter
authors.initials: P
authors.lastname: Mwaba
authors.affiliation: Institute for Infection and Immunity, St Georges University of London, London, UK.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Harrison
authors.affiliation: National Tuberculosis and Leprosy Control Program, Ministry of Health and Socio-Welfare, Dar es Salaam, Tanzania.
authors.forename: Saidi
authors.initials: S
authors.lastname: Egwaga
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: shabbar.jaffar@lshtm.ac.uk.
authors.forename: Shabbar
authors.initials: S
authors.lastname: Jaffar
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use; D003153:Community Health Services / Q000379:methods*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D008297:Male; D016919:Meningitis, Cryptococcal / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality*; D008875:Middle Aged; D010349:Patient Compliance; D013636:Tanzania / Q000453:epidemiology; D016896:Treatment Outcome; D015024:Zambia / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents; D000935:Antifungal Agents