title: Antiretroviral Pre-Exposure Prophylaxis Does Not Enhance Immune Responses to HIV in Exposed but Uninfected Persons.
abstract: BACKGROUND
  Antiretroviral preexposure prophylaxis (PrEP), using daily oral combination tenofovir disoproxil fumarate plus emtricitabine, is an effective human immunodeficiency virus (HIV) prevention strategy for populations at high risk of HIV acquisition. Although the primary mode of action for the protective effect of PrEP is probably direct antiviral activity, nonhuman primate studies suggest that PrEP may also allow for development of HIV-specific immune responses, hypothesized to result from aborted HIV infections providing a source of immunologic priming. We sought to evaluate whether PrEP affects the development of HIV-specific immune response in humans.
  
  
  RESULTS
  Within a PrEP clinical trial among high-risk heterosexual African men and women, we detected HIV-specific CD4(+) and CD8(+) peripheral blood T-cell responses in 10%-20% of 247 subjects evaluated. The response rate and magnitude of T-cell responses did not vary significantly between those assigned PrEP versus placebo, and no significant difference between those assigned PrEP and placebo was observed in measures of innate immune function.
  
  
  CONCLUSIONS
  We found no evidence to support the hypothesis that PrEP alters either the frequency or magnitude of HIV-specific immune responses in HIV-1-exposed seronegative individuals. These results suggest that PrEP is unlikely to serve as an immunologic prime to aid protection by a putative HIV vaccine.
authors.affiliation: Vaccine and Infectious Disease Division.
authors.forename: Laura
authors.initials: L
authors.lastname: Pattacini
authors.affiliation: Department of Global Health Department of Epidemiology.
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Murnane
authors.affiliation: Department of Global Health Department of Epidemiology Department of Medicine.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.affiliation: Vaccine and Infectious Disease Division.
authors.forename: Tayler R
authors.initials: TR
authors.lastname: Fluharty
authors.affiliation: Department of Global Health.
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Thomas
authors.affiliation: Department of Global Health Department of Obstetrics and Gynecology Centre for Microbiology Research.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bukusi
authors.affiliation: Department of Medicine, Makerere University, Kampala, Uganda.
authors.forename: Elly
authors.initials: E
authors.lastname: Katabira
authors.affiliation: Department of Global Health Centre for Clinical Research, Kenya Medical Research Institute, Nairobi.
authors.forename: Nelly
authors.initials: N
authors.lastname: Mugo
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center Department of Global Health.
authors.forename: Deborah
authors.initials: D
authors.lastname: Donnell
authors.affiliation: Department of Global Health Department of Medicine Department of Pediatrics, University of Washington, Seattle.
authors.forename: Jairam R
authors.initials: JR
authors.lastname: Lingappa
authors.affiliation: Department of Global Health Department of Epidemiology Department of Medicine.
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Marzinke
authors.affiliation: Vaccine and Infectious Disease Division Department of Global Health Department of Medicine.
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.affiliation: Vaccine and Infectious Disease Division Department of Global Health.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Lund
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D000349:Africa; D000818:Animals; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018890:Chemoprevention / Q000379:methods*; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068679:Emtricitabine; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage; D010919:Placebos / Q000008:administration & dosage; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D000068698:Tenofovir; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D010919:Placebos; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine
keywords: HIV-1; T-lymphocyte; cellular immunity; prevention of sexual transmission