title: Efficacy of preexposure prophylaxis for HIV-1 prevention among high-risk heterosexuals: subgroup analyses from a randomized trial.
abstract: BACKGROUND
  Daily oral antiretroviral preexposure prophylaxis (PrEP) is a promising strategy for prevention of HIV-1 acquisition. Three clinical trials demonstrated PrEP efficacy; however, two PrEP trials among women did not find protection against HIV-1. One hypothesis proposed for these divergent results is that PrEP efficacy may be reduced in populations with higher HIV-1 incidence.
  
  
  METHODS
  Using data from the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral tenofovir (TDF) and emtricitabine/tenofovir (FTC/TDF) PrEP among heterosexual HIV-1 serodiscordant couples from Kenya and Uganda, we assessed PrEP efficacy among subgroups at higher risk for HIV-1 acquisition, including subgroups of women with high HIV-1 incidence.
  
  
  RESULTS
  The overall placebo arm HIV-1 incidence was 2.0 per 100 person-years. Among higher risk subgroups, placebo arm HIV-1 incidence ranged from 3.9 to 6.6 per 100 person-years. In all subgroups, PrEP was protective against HIV-1 acquisition, with efficacy point estimates ranging from 64 to 84%. Among subgroups of women with placebo-arm HIV-1 incidence more than 5.0, efficacy estimates ranged from 64 to 84%. Monthly visit attendance for PrEP refills and tenofovir detection in plasma were high.
  
  
  CONCLUSIONS
  Among higher-risk subgroups in the Partners PrEP Study, including groups solely of higher-risk women, both TDF alone and combined FTC/TDF PrEP had consistently high efficacy for HIV-1 protection. PrEP, when used with high adherence, is a highly effective prevention strategy for higher risk heterosexuals. Prioritizing PrEP for persons at high risk of HIV-1 will maximize its prevention impact.
authors.affiliation: aDepartment of Epidemiology bDepartment of Global Health cDepartment of Medicine, University of Washington, Seattle, Washington, USA dDepartment of Obstetrics and Gynaecology, University of Nairobi eDepartment of Obstetrics & Gynaecology, Kenyatta National Hospital, Nairobi, Kenya fDivision of HIV/AIDS Prevention, National Center for HIV, Viral Hepatitis, STD and TB Prevention, CDC-Uganda, Entebbe, Uganda gDivision of Infectious Diseases and Tropical Pediatrics, Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland hStatistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA iCenters for Disease Control and Prevention, Atlanta, Georgia, USA. *Members of the Partners PrEP Study Team listed at end of paper.
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Murnane
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.forename: Nelly
authors.initials: N
authors.lastname: Mugo
authors.forename: James D
authors.initials: JD
authors.lastname: Campbell
authors.forename: Deborah
authors.initials: D
authors.lastname: Donnell
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bukusi
authors.forename: Andrew
authors.initials: A
authors.lastname: Mujugira
authors.forename: Jordan
authors.initials: J
authors.lastname: Tappero
authors.forename: Erin M
authors.initials: EM
authors.lastname: Kahle
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Thomas
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D018890:Chemoprevention / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D020010:Heterosexuality; D006801:Humans; D015994:Incidence; D007630:Kenya; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage; D010919:Placebos / Q000008:administration & dosage; D000068698:Tenofovir; D016896:Treatment Outcome; D014454:Uganda
chemical_list: D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D010919:Placebos; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine