title: Complete protection from repeated vaginal simian-human immunodeficiency virus exposures in macaques by a topical gel containing tenofovir alone or with emtricitabine.
abstract: New-generation gels that deliver potent antiretroviral drugs against human immunodeficiency virus type 1 have renewed hopes for topical prophylaxis as a prevention strategy. Previous preclinical research with monkey models suggested that high concentrations and drug combinations are needed for high efficacy. We evaluated two long-acting reverse transcriptase inhibitors, tenofovir (TFV) and emtricitabine (FTC), by using a twice-weekly repeat challenge macaque model and showed that a preexposure vaginal application of gel with 1% TFV alone or in combination with 5% FTC fully protected macaques from a total of 20 exposures to simian-human immunodeficiency virus SF162p3. FTC and TFV were detected in plasma 30 min after vaginal application, suggesting rapid absorption. FTC was detected more frequently than TFV and showed higher levels, reflecting the fivefold-higher concentration of this drug than of TFV. Two of 12 repeatedly exposed but protected macaques showed limited T-cell priming, which did not induce resistance to infection when macaques were rechallenged. Thus, single drugs with durable antiviral activity can provide highly effective topical prophylaxis and overcome the need for noncoital use or for drug combinations which are more complex and costly to formulate and approve.
authors: Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
authors: Urvi M
authors: UM
authors: Parikh
authors: Charles
authors: C
authors: Dobard
authors: Sunita
authors: S
authors: Sharma
authors: Mian-er
authors: ME
authors: Cong
authors: Hongwei
authors: H
authors: Jia
authors: Amy
authors: A
authors: Martin
authors: Chou-Pong
authors: CP
authors: Pau
authors: Debra L
authors: DL
authors: Hanson
authors: Patricia
authors: P
authors: Guenthner
authors: James
authors: J
authors: Smith
authors: Ellen
authors: E
authors: Kersh
authors: J Gerardo
authors: JG
authors: Garcia-Lerma
authors: Francis J
authors: FJ
authors: Novembre
authors: Ron
authors: R
authors: Otten
authors: Thomas
authors: T
authors: Folks
authors: Walid
authors: W
authors: Heneine
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000282:Administration, Intravaginal; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D005782:Gels / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008254:Macaca nemestrina; D063065:Organophosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects*; D000068698:Tenofovir; D016896:Treatment Outcome; D014621:Vagina / Q000821:virology*
chemical_list: D019380:Anti-HIV Agents; D005782:Gels; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine