title: Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women.
abstract: OBJECTIVE
  To assess the local and systemic safety of dapivirine vaginal gel vs. placebo gel as well as the systemic absorption of dapivirine in healthy, HIV-negative women.
  
  
  METHODS
  Two prospective, randomized, double-blind, placebo-controlled phase I/II studies were conducted at five research centers, four in Africa and one in Belgium. A total of 119 women used dapivirine gel (concentrations of 0.001, 0.002, 0.005, or 0.02%), and 28 used placebo gel twice daily for 42 days. The primary endpoints were colposcopic findings, adverse events, Division of AIDS grade 3 or grade 4 laboratory values, and plasma levels of dapivirine.
  
  
  RESULTS
  Safety data were similar for the dapivirine and placebo gels. None of the adverse events with incidence more than 5% occurred with greater frequency in the dapivirine than placebo groups. Similar percentages of placebo and dapivirine gel users had adverse events that were considered by the investigator to be related to study gel. A total of five serious adverse events occurred in the two studies, and none was assessed as related to study gel. Mean plasma concentrations of dapivirine were approximately dose proportional, and, within each dose group, mean concentrations were similar on days 7, 28, and 42. The maximum observed mean concentration was 474 pg/ml in the 0.02% gel group on day 28. Two weeks after the final application of study gel, mean concentrations decreased to 5 pg/ml or less.
  
  
  CONCLUSIONS
  Twice daily administration of dapivirine vaginal gel for 42 days was safe and well tolerated with low systemic absorption in healthy, HIV-negative women suggesting that continued development is warranted.
authors: International Partnership for Microbicides, Silver Spring, Maryland 20910, USA.
authors: Annalene M
authors: AM
authors: Nel
authors: Paul
authors: P
authors: Coplan
authors: Janneke H
authors: JH
authors: van de Wijgert
authors: Saidi H
authors: SH
authors: Kapiga
authors: Claire
authors: C
authors: von Mollendorf
authors: Eveline
authors: E
authors: Geubbels
authors: Joseph
authors: J
authors: Vyankandondera
authors: Helen V
authors: HV
authors: Rees
authors: Gileard
authors: G
authors: Masenga
authors: Ireen
authors: I
authors: Kiwelu
authors: Jocelyn
authors: J
authors: Moyes
authors: Shanique C
authors: SC
authors: Smythe
mesh_terms: D000282:Administration, Intravaginal; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D002584:Cervix Uteri / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000517:prevention & control; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006801:Humans; D008875:Middle Aged; D010349:Patient Compliance; D017060:Patient Satisfaction; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D014621:Vagina / Q000187:drug effects / Q000473:pathology; D014622:Vaginal Creams, Foams, and Jellies / Q000009:adverse effects; D014844:Vulva / Q000187:drug effects / Q000473:pathology; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D011743:Pyrimidines; D014622:Vaginal Creams, Foams, and Jellies; D054303:HIV Reverse Transcriptase; C481671:Dapivirine