title: Uptake of antiretroviral therapy and male circumcision after community-based HIV testing and strategies for linkage to care versus standard clinic referral: a multisite, open-label, randomised controlled trial in South Africa and Uganda.
abstract: Male circumcision decreases HIV acquisition by 60%, and antiretroviral therapy (ART) almost eliminates HIV transmission from HIV-positive people who are virally suppressed; however, coverage of these interventions has lagged behind targets. We aimed to assess whether community-based HIV testing with counsellor support and point-of-care CD4 cell count testing would increase uptake of ART and male circumcision.
  
  
  
  We did this multisite, open-label, randomised controlled trial in six research-naive communities in rural South Africa and Uganda. Eligible HIV-positive participants (aged ≥16 years) were randomly assigned (1:1:1) in a factorial design to receive lay counsellor clinic linkage facilitation, lay counsellor follow-up home visits, or standard-of-care clinic referral, and then (1:1) either point-of-care CD4 cell count testing or referral for CD4 testing. HIV-negative uncircumcised men (aged 16-49 years) who could receive secure mobile phone text messages were randomly assigned (1:1:1) to receive text message reminders, lay counsellor visits, or standard clinic referral. The study biostatistician generated the randomisation schedule via a computer-generated random number program with varying block sizes (multiples of six or three) stratified by country. Primary outcomes for HIV-positive people were obtaining a CD4 cell count, linkage to an HIV clinic, ART initiation, and viral suppression at 9 months, and for HIV-negative uncircumcised men were visiting a circumcision facility and uptake of male circumcision at 3 months. We assessed social harms as a safety outcome throughout the study. We did the primary analyses by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02038582.
  
  
  
  Between June 6, 2013, and March 11, 2015, 15 332 participants were tested. 2339 (15%) participants tested HIV positive, of whom 1325 (57%) were randomly assigned to receive lay counsellor clinic linkage facilitation (n=437), lay counsellor follow-up home visits (n=449), or standard clinic referral (n=439), and then point-of-care CD4 cell testing (n=206, n=220, and n=213, respectively) or referral for CD4 testing (n=231, n=229, and n=226, respectively). 12 993 (85%) participants tested HIV negative, of whom 750 (6%) uncircumcised men were randomly assigned to receive clinic referral (n=230), text message reminders (n=288), or lay counsellor follow-up visits (n=232). 1218 (93%) of 1303 HIV-positive participants were linked to care, but only 488 (37%) participants initiated ART. Overall, 635 (50%) of 1272 HIV-positive individuals achieved viral suppression at 9 months: 219 (52%) of 419 participants in the clinic facilitation group, 202 (47%) of 431 participants in the lay counsellor follow-up group, and 214 (51%) of 422 participants in the clinic referral group, with no significant differences between groups (p=0·668 for clinic facilitation and p=0·273 for lay counsellor follow-up vs clinic referral). 523 (72%) of 734 HIV-negative men visited a circumcision facility, with no difference between groups. 62 (28%) of 224 men were circumcised in the male circumcision clinic referral group compared with 137 (48%) of 284 men in the text message reminder group (relative risk 1·72, 95% CI 1·36-2·17; p<0·0001) and 106 (47%) of 226 men in the lay counsellor follow-up group (1·67, 1·29-2·14; p=0·0001). No cases of study-related social harm were reported, including probing about partnership separation, unintended disclosure, gender-based violence, and stigma.
  
  
  
  All the community-based strategies achieved high rates of linkage of HIV-positive people to HIV clinics, roughly a third of whom initiated ART, and of those more than 80% were virally suppressed at 9 months. Uptake of male circumcision was almost two-times higher in men who received text message reminders or lay counsellor visits than in those who received standard-of-care clinic referral. Clinic barriers to ART initiation should be addressed in future strategies to increase the proportion of HIV-positive people accessing treatment and achieving viral suppression.
  
  
  
  National Institute of Allergy and Infectious Diseases, National Institutes of Health.
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA; School of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Electronic address: rbarnaba@uw.edu.
authors.forename: Ruanne V
authors.initials: RV
authors.lastname: Barnabas
authors.affiliation: Human Sciences Research Council, Sweetwaters, KwaZulu-Natal, South Africa.
authors.forename: Heidi
authors.initials: H
authors.lastname: van Rooyen
authors.affiliation: Integrated Community-Based Initiatives, Kabwohe, Uganda.
authors.forename: Elioda
authors.initials: E
authors.lastname: Tumwesigye
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Brantley
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA; School of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.affiliation: Human Sciences Research Council, Sweetwaters, KwaZulu-Natal, South Africa; Developmental Pathways for Health Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Alastair
authors.initials: A
authors.lastname: van Heerden
authors.affiliation: Integrated Community-Based Initiatives, Kabwohe, Uganda.
authors.forename: Bosco
authors.initials: B
authors.lastname: Turyamureeba
authors.affiliation: Human Sciences Research Council, Sweetwaters, KwaZulu-Natal, South Africa.
authors.forename: Philip
authors.initials: P
authors.lastname: Joseph
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA.
authors.forename: Meighan
authors.initials: M
authors.lastname: Krows
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA.
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Thomas
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA.
authors.forename: Torin T
authors.initials: TT
authors.lastname: Schaafsma
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA; Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Hughes
authors.affiliation: Department of Global Health, University of Washington, Seattle, WA, USA; School of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002944:Circumcision, Male; D003153:Community Health Services; D003376:Counseling; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008403:Mass Screening; D019095:Point-of-Care Systems; D012017:Referral and Consultation; D013019:South Africa / Q000453:epidemiology; D014454:Uganda / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents