title: Symptoms, Side Effects and Adherence in the iPrEx Open-Label Extension.
abstract: BACKGROUND
  Blinded clinical trials have reported a modest and transient "start-up syndrome" with initiation of tenofovir-based pre-exposure prophylaxis (PrEP). We evaluate this phenomenon and its effect on adherence in an open-label PrEP study.
  
  
  METHODS
  In the iPrEx open-label extension (OLE) study, an 18-month open-label, multi-site PrEP cohort taking daily oral co-formulated tenofovir/emtricitabine, we examined the prevalence and duration of PrEP-associated symptoms and their effect on adherence, assessed by drug levels in dried blood spots tested monthly for the first 3 months.
  
  
  RESULTS
  Symptom reports peaked within the first month, with 39% reporting potentially PrEP-related symptoms compared to 22% at baseline. Symptoms largely resolved to pre-PrEP levels by 3 months.Symptoms varied substantially in frequency by study site (range in 1-month symptoms: 11% to 70%). Nongastrointestinal (GI) symptoms were not associated with adherence (odds ratio [OR] = 1.2, 95% confidence interval [CI], .4-3.7); however, GI-associated symptoms in the first 4 weeks were inversely associated with adherence at 4 weeks (OR = 0.47, 95% CI, .23-.96). Reports of GI symptoms were associated with 7% (95% CI, 4%-11%) of suboptimal adherence in this cohort.
  
  
  CONCLUSIONS
  PrEP-associated symptoms in the open-label setting occur in a minority of users and largely resolve within 3 months. GI symptoms are associated with a modest reduction in PrEP adherence, but good adherence is possible even in the presence of frequent symptom reports.
  
  
  BACKGROUND
  Clinicaltrials.govNCT00458393.
authors.affiliation: University of California, San Francisco.
authors.forename: David V
authors.initials: DV
authors.lastname: Glidden
authors.affiliation: University of Michigan, Ann Arbor.
authors.forename: K Rivet
authors.initials: KR
authors.lastname: Amico
authors.affiliation: Bridge HIV, San Francisco Department of Public Health, California.
authors.forename: Albert Y
authors.initials: AY
authors.lastname: Liu
authors.affiliation: John Stroger Hospital of Cook County, Chicago, Illinois.
authors.forename: Sybil G
authors.initials: SG
authors.lastname: Hosek
authors.affiliation: University of Colorado, Denver, Aurora.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Anderson
authors.affiliation: Bridge HIV, San Francisco Department of Public Health, California.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Buchbinder
authors.affiliation: University of Washington, Seattle.
authors.forename: Vanessa
authors.initials: V
authors.lastname: McMahan
authors.affiliation: Fenway Health and Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Mayer
authors.affiliation: National Institute of Allergy and Infectious Diseases, Rockville, Maryland.
authors.forename: Burns
authors.initials: B
authors.lastname: David
authors.affiliation: Projeto Praça Onze, Hospital Escola São Francisco de Assis and Universidade Federal do Rio de Janeiro, and.
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.affiliation: Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro, Brazil.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.affiliation: Investigaciones Médicas en Salud, Lima, Peru.
authors.forename: Juan
authors.initials: J
authors.lastname: Guanira
authors.affiliation: Gladstone Institute of Virology and San Francisco AIDS Foundation, California.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Grant
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D000068679:Emtricitabine / Q000009:adverse effects*; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D008297:Male; D055118:Medication Adherence; D065129:Pre-Exposure Prophylaxis; D000068698:Tenofovir / Q000009:adverse effects*
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir; D000068679:Emtricitabine
keywords: HIV prevention; PrEP; pre-exposure prophylaxis; tenofovir/emtricitabine