title: Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1-Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda.
abstract: Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.
  
  
  
  Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7-6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0-0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP.
  
  
  
  Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.
authors.affiliation: Department of Global Health, University of Washington, Seattle, Seattle, Washington, United States of America.|Department of Medicine, University of Washington, Seattle, Seattle, Washington, United States of America.|Department of Epidemiology, University of Washington, Seattle, Seattle, Washington, United States of America.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.affiliation: Department of Global Health, University of Washington, Seattle, Seattle, Washington, United States of America.|Department of Epidemiology, University of Washington, Seattle, Seattle, Washington, United States of America.
authors.forename: Renee
authors.initials: R
authors.lastname: Heffron
authors.affiliation: Department of Global Health, University of Washington, Seattle, Seattle, Washington, United States of America.
authors.forename: Lara
authors.initials: L
authors.lastname: Kidoguchi
authors.affiliation: Department of Global Health, University of Washington, Seattle, Seattle, Washington, United States of America.|Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Nelly R
authors.initials: NR
authors.lastname: Mugo
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala, Uganda.
authors.forename: Elly
authors.initials: E
authors.lastname: Katabira
authors.affiliation: Department of Global Health, University of Washington, Seattle, Seattle, Washington, United States of America.|Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bukusi
authors.affiliation: Kabwohe Clinical Research Center, Kabwohe, Uganda.
authors.forename: Stephen
authors.initials: S
authors.lastname: Asiimwe
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Haberer
authors.affiliation: Department of Global Health, University of Washington, Seattle, Seattle, Washington, United States of America.
authors.forename: Jennifer
authors.identifier: 0000-0002-3080-6254
authors.initials: J
authors.lastname: Morton
authors.affiliation: College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ngure
authors.affiliation: Infectious Disease Institute, Makerere University, Kampala, Uganda.
authors.forename: Nulu
authors.initials: N
authors.lastname: Bulya
authors.affiliation: Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya.
authors.forename: Josephine
authors.initials: J
authors.lastname: Odoyo
authors.affiliation: Kabwohe Clinical Research Center, Kabwohe, Uganda.
authors.forename: Edna
authors.identifier: 0000-0003-4255-2818
authors.initials: E
authors.lastname: Tindimwebwa
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Craig
authors.initials: C
authors.lastname: Hendrix
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Marzinke
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Norma C
authors.initials: NC
authors.lastname: Ware
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.|Harvard Global, Cambridge, Massachusetts, United States of America.
authors.forename: Monique A
authors.initials: MA
authors.lastname: Wyatt
authors.affiliation: Department of Global Health, University of Washington, Seattle, Seattle, Washington, United States of America.
authors.forename: Susan
authors.initials: S
authors.lastname: Morrison
authors.affiliation: Department of Global Health, University of Washington, Seattle, Seattle, Washington, United States of America.
authors.forename: Harald
authors.identifier: 0000-0002-2034-2150
authors.initials: H
authors.lastname: Haugen
authors.affiliation: Department of Global Health, University of Washington, Seattle, Seattle, Washington, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mujugira
authors.affiliation: Department of Global Health, University of Washington, Seattle, Seattle, Washington, United States of America.|Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Deborah
authors.initials: D
authors.lastname: Donnell
authors.affiliation: Department of Global Health, University of Washington, Seattle, Seattle, Washington, United States of America.|Department of Medicine, University of Washington, Seattle, Seattle, Washington, United States of America.|Department of Epidemiology, University of Washington, Seattle, Seattle, Washington, United States of America.
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D019033:Delivery of Health Care, Integrated / Q000379:methods / Q000458:organization & administration; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control*; D006679:HIV Seropositivity / Q000188:drug therapy / Q000453:epidemiology; D015497:HIV-1; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D008297:Male; D055118:Medication Adherence; D065129:Pre-Exposure Prophylaxis / Q000379:methods / Q000706:statistics & numerical data; D011446:Prospective Studies; D012747:Sexual Partners; D014454:Uganda / Q000453:epidemiology; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents