title: Prophylactic treatment with a novel bioadhesive gel formulation containing aciclovir and tenofovir protects from HSV-2 infection.
abstract: OBJECTIVE
  Over-the-counter access to an inexpensive, effective topical microbicide could reduce the transmission of HIV and would increase women's control over their health and eliminate the need to obtain their partners' consent for prophylaxis. Chronic infection with herpes simplex virus 2 (HSV-2), also known as human herpes virus 2, has been shown to facilitate HIV infection and speed the progression to immunodeficiency disease. Our objective is to develop a drug formulation that protects against both HSV-2 and HIV infection and adheres to the vaginal surface with extended residence time.
  
  
  METHODS
  We developed a formulation using two approved antiviral active pharmaceutical ingredients, aciclovir and tenofovir, in a novel bioadhesive vaginal delivery platform (designated SR-2P) composed of two polymers, poloxamer 407 NF (Pluronic(®) F-127) and polycarbophil USP (Noveon(®) AA-1). The efficacy of the formulation to protect from HSV-2 infection was tested in vitro and in vivo. In addition to its efficacy, it is essential for a successful microbicide to be non-irritating to the vaginal mucosa. We therefore tested our SR-2P platform gel in the FDA gold-standard microbicide safety model in rabbits and also in a rat vaginal irritation model.
  
  
  RESULTS
  Our studies indicated that SR-2P containing 1% aciclovir and 5% tenofovir protects (i) Vero cells from HSV-2 infection in vitro and (ii) mice from HSV-2 infection in vivo. Our results further demonstrated that SR-2P was not irritating in either vaginal irritation model.
  
  
  CONCLUSIONS
  We conclude that SR-2P containing aciclovir and tenofovir may be a suitable candidate microbicide to protect humans from vaginal HSV-2 infection.
authors.affiliation: Pharmaceutical Development, Biosciences Division, SRI International, Menlo Park, CA, USA.
authors.forename: Gita N
authors.initials: GN
authors.lastname: Shankar
authors.affiliation: Palo Alto Veterans Institute for Research (PAVIR), VA Palo Alto Health Care System, Palo Alto, CA, USA carstalt@gmail.com.
authors.forename: Carsten
authors.initials: C
authors.lastname: Alt
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage / Q000009:adverse effects; D000212:Acyclovir / Q000008:administration & dosage* / Q000009:adverse effects; D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006558:Herpes Genitalis / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D008807:Mice, Inbred BALB C; D063065:Organophosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D020442:Poloxamer / Q000008:administration & dosage / Q000009:adverse effects; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D000068698:Tenofovir; D016896:Treatment Outcome; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage* / Q000009:adverse effects; D014709:Vero Cells
chemical_list: D000180:Acrylic Resins; D000890:Anti-Infective Agents; D063065:Organophosphonates; D014622:Vaginal Creams, Foams, and Jellies; D020442:Poloxamer; C030312:calcium polycarbophil; D000068698:Tenofovir; D000225:Adenine; D000212:Acyclovir
keywords: HSV-2; acyclovir; antiviral; microbicide; vaginal