Vaccines
Several preventative vaccine candidates have elicited anti-glycoprotein D (gD) neutralising antibody responses, but unfortunately none have been shown to confer protection against HSV-1 or HSV-2 acquisition.[68]Belshe RB, Leone PA, Bernstein DI, et al. Efficacy results of a trial of a herpes simplex vaccine. N Engl J Med. 2012;366:34-43.
http://www.ncbi.nlm.nih.gov/pubmed/22216840?tool=bestpractice.com
[69]Gilbert PB, Excler JL, Tomaras GD, et al. Antibody to HSV gD peptide induced by vaccination does not protect against HSV-2 infection in HSV-2 seronegative women. PLoS One. 2017 May 11;12(5):e0176428.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176428
http://www.ncbi.nlm.nih.gov/pubmed/28493891?tool=bestpractice.com
A number of candidate therapeutic vaccines are in clinical trials, but none have been approved.
Helicase-primase inhibitors
Viral helicase is an essential enzyme for viral replication. Helicase inhibitors have the potential to specifically prevent viral replication. Amenamevir had antiviral activity in a phase 2 clinical trial.[70]Tyring S, Wald A, Zadeikis N, et al. ASP2151 for the treatment of genital herpes: a randomized, double-blind, placebo- and valacyclovir-controlled, dose-finding study. J Infect Dis. 2012 Apr 1;205(7):1100-10.
http://www.ncbi.nlm.nih.gov/pubmed/22351940?tool=bestpractice.com
Pritelivir demonstrated reduction in genital shedding and lesions in two phase 2 trials, and a phase 3 amendment for aciclovir-resistant mucocutaneous HSV in immunocompromised subjects is underway.[71]Wald A, Corey L, Timmler B, et al. Helicase-primase inhibitor pritelivir for HSV-2 infection. N Engl J Med. 2014 Jan 16;370(3):201-10.
http://www.nejm.org/doi/full/10.1056/NEJMoa1301150#t=article
http://www.ncbi.nlm.nih.gov/pubmed/24428466?tool=bestpractice.com
[72]Wald A, Timmler B, Magaret A, et al. Effect of pritelivir compared with valacyclovir on genital HSV-2 shedding in patients with frequent recurrences: a randomized clinical trial. JAMA. 2016 Dec 20;316(23):2495-2503. Erratum in: JAMA. 2017 Feb 14;317(6):648.
https://jamanetwork.com/journals/jama/fullarticle/2593569
http://www.ncbi.nlm.nih.gov/pubmed/27997653?tool=bestpractice.com
[73]US National Library of Medicine. ClinicalTrials.gov. Trial on efficacy and safety of pritelivir tablets for treatment of acyclovir-resistant mucocutaneous HSV (herpes simplex virus) infections in immunocompromised subjects (PRIOH-1). Nov 2021 [internet publication].
https://clinicaltrials.gov/ct2/show/record/NCT03073967?view=record
Tenofovir-based therapies
In the context of HIV-prevention studies, oral tenofovir, oral tenofovir/emtricitabine, and pericoital vaginal tenofovir gel have been shown to decrease the risk of HSV-2 acquisition by 30% to 50%.[74]Celum C, Morrow RA, Donnell D, et al. Daily oral tenofovir and emtricitabine-tenofovir preexposure prophylaxis reduces herpes simplex virus type 2 acquisition among heterosexual HIV-1-uninfected men and women: a subgroup analysis of a randomized trial. Ann Intern Med. 2014 Jul 1;161(1):11-9.
http://www.ncbi.nlm.nih.gov/pubmed/24979446?tool=bestpractice.com
However, when given to HSV-2-infected women, neither oral tenofovir nor vaginal tenofovir gel decreased genital HSV-2 shedding or recurrences.[75]Celum C, Hong T, Cent A, et al. Herpes simplex virus type 2 acquisition among HIV-1-infected adults treated with tenofovir disoproxyl fumarate as part of combination antiretroviral therapy: results from the ACTG A5175 PEARLS Study. J Infect Dis. 2017 Mar 15;215(6):907-10.
https://academic.oup.com/jid/article/215/6/907/2964641
http://www.ncbi.nlm.nih.gov/pubmed/28453835?tool=bestpractice.com
[76]Bender Ignacio RA, Perti T, Magaret AS, et al. Oral and vaginal tenofovir for genital herpes simplex virus type 2 shedding in immunocompetent women: a double-blind, randomized, cross-over trial. J Infect Dis. 2015 Dec 15;212(12):1949-56.
http://www.ncbi.nlm.nih.gov/pubmed/26044291?tool=bestpractice.com
Due to very low quality of evidence, a Cochrane review found the effects of tenofovir in the management of HSV to be uncertain.[77]Obiero J, Ogongo P, Mwethera PG, et al. Topical microbicides for preventing sexually transmitted infections. Cochrane Database Syst Rev. 2021 Mar 13;3:CD007961.
https://www.doi.org/10.1002/14651858.CD007961.pub3
http://www.ncbi.nlm.nih.gov/pubmed/33719075?tool=bestpractice.com
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For sexually active women, do topical microbicides prevent sexually transmitted infections (STIs)?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.3648/fullShow me the answer
Monoclonal antibodies
MB66 is an investigational vaginal film that includes a combination of anti-HIV (VRC01-N) and anti-HSV (HSV8-N) monoclonal antibodies. The HSV8-N antibody has specificity for a HSV-1/2 envelope epitope.[78]ClinicalTrials.gov. Clinical trial NCT02579083: Vaginal antibody safety trial: safety study of monoclonal antibodies to reduce the vaginal transmission of herpes simplex virus (HSV) and human immunodeficiency virus (HIV) (VAST). October 2017.
https://clinicaltrials.gov/ct2/show/NCT02579083