title: Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa.
abstract: BACKGROUND
  This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing vaginal ring as an HIV prevention technology for women.
  
  
  OBJECTIVE
  The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered vaginal ring containing the antiretroviral microbicide, dapivirine, with a matching placebo ring among women from four countries in sub-Saharan Africa.
  
  
  METHODS
  280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine vaginal ring (25 mg) and 140 women to a matching placebo ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned rings from dapivirine ring users were determined post-trial. Participant acceptability and adherence to ring use were assessed by self-reports.
  
  
  RESULTS
  No safety concerns or clinically relevant differences were observed between the dapivirine and placebo ring groups. Plasma dapivirine concentrations immediately prior to ring removal were similar after removal of the first and third ring, suggesting consistent ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used rings and corresponding plasma concentrations. Self-reported adherence to daily use of the vaginal rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective.
  
  
  CONCLUSIONS
  The dapivirine vaginal ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of combination HIV prevention approaches for women.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01071174.
authors.affiliation: International Partnership for Microbicides, Silver Spring, Maryland, United States of America.
authors.forename: Annalene
authors.initials: A
authors.lastname: Nel
authors.affiliation: The Desmond Tutu HIV Foundation, University of Cape Town, Cape Town, South Africa.
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.affiliation: Kenya Medical Research Institute, Kisumu, Kenya.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bukusi
authors.affiliation: Be Part Yoluntu Centre, Paarl, South Africa.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hellstrӧm
authors.affiliation: Qhakaza Mbokodo Research Clinic, Ladysmith, South Africa.
authors.forename: Philip
authors.initials: P
authors.lastname: Kotze
authors.affiliation: Madibeng Centre for Research, Brits, South Africa.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Louw
authors.affiliation: University of North Carolina Project, Lilongwe, Malawi.
authors.forename: Francis
authors.initials: F
authors.lastname: Martinson
authors.affiliation: Kilimanjaro Christian Medical Centre, Moshi, Tanzania.
authors.forename: Gileard
authors.initials: G
authors.lastname: Masenga
authors.affiliation: RTI International, San Francisco, California, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Montgomery
authors.affiliation: Maternal, Adolescent and Child Health, Edendale, South Africa.
authors.forename: Nelisiwe
authors.initials: N
authors.lastname: Ndaba
authors.affiliation: RTI International, San Francisco, California, United States of America.
authors.forename: Ariane
authors.initials: A
authors.lastname: van der Straten
authors.affiliation: International Partnership for Microbicides, Silver Spring, Maryland, United States of America.
authors.forename: Neliëtte
authors.initials: N
authors.lastname: van Niekerk
authors.affiliation: International Partnership for Microbicides, Silver Spring, Maryland, United States of America.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Woodsong
mesh_terms: D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D003274:Contraceptive Devices, Female / Q000009:adverse effects*; D003710:Demography; D005260:Female; D006801:Humans; D015994:Incidence; D017533:Marital Status; D010342:Patient Acceptance of Health Care; D010349:Patient Compliance; D011743:Pyrimidines / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D057566:Self Report; D012725:Sexual Behavior; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D011743:Pyrimidines; C481671:Dapivirine