title: Delayed maturation of antibody avidity but not seroconversion in rhesus macaques infected with simian HIV during oral pre-exposure prophylaxis.
abstract: BACKGROUND
  Pre-exposure prophylaxis (PrEP) is a novel intervention strategy for the prevention HIV transmission. Because several clinical trials are at various stages of completion, it is important to understand the impact of PrEP treatment on the development of the immune response to HIV, particularly in individuals who exhibit breakthrough infections despite PrEP.
  
  
  METHODS
  A model of HIV infection, using rhesus macaques and the simian/human immunodeficiency virus (SHIV), was used to evaluate the effects of PrEP on the evolution of the humoral immune response. Time to seroconversion, neutralizing and binding antibody levels, and antibody avidity were measured in 12 rhesus macaques infected during daily or intermittent PrEP with FTC (emtricitabine) or Truvada (FTC/tenofovir combination) and compared with 11 untreated, simian HIV-infected controls.
  
  
  RESULTS
  Macaques that became infected while receiving PrEP exhibited significantly lower peak virus loads during acute infection as compared with untreated animals. Although the timing of seroconversion and SHIV binding and neutralizing antibody levels were not impacted by treatment, lower maturation rates of antibody avidity for anti-p27, gp120, gp160, and gp41 were observed.
  
  
  CONCLUSIONS
  This study suggests that reduced virus loads associated with PrEP treatment have little impact on timing of seroconversion and neutralizing/binding antibody levels; however, maturation of antibody avidity was suppressed.
authors.affiliation: Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. czv2@cdc.gov
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Curtis
authors.forename: M Susan
authors.initials: MS
authors.lastname: Kennedy
authors.forename: Amara
authors.initials: A
authors.lastname: Luckay
authors.forename: Mian-Er
authors.initials: ME
authors.lastname: Cong
authors.forename: Ae S
authors.initials: AS
authors.lastname: Youngpairoj
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.forename: James
authors.initials: J
authors.lastname: Smith
authors.forename: Debra
authors.initials: D
authors.lastname: Hanson
authors.forename: Walid
authors.initials: W
authors.lastname: Heneine
authors.forename: S Michele
authors.initials: SM
authors.lastname: Owen
authors.forename: J Gerardo
authors.initials: JG
authors.lastname: García-Lerma
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood / Q000502:physiology*; D000915:Antibody Affinity; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D004338:Drug Combinations; D000068679:Emtricitabine; D006678:HIV; D015483:HIV Antibodies / Q000502:physiology; D054298:Human Immunodeficiency Virus Proteins / Q000276:immunology; D008253:Macaca mulatta; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology*; D000068698:Tenofovir; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D000914:Antibodies, Viral; D004338:Drug Combinations; D015483:HIV Antibodies; D054298:Human Immunodeficiency Virus Proteins; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine