Gilda Tachedjian

Burnet Institute, Melbourne, VIC

Last reviewed: August 2019

Background

 Microbicides are chemical entities that can be formulated in gels, films, tablets, capsules or intravaginal rings (IVR) for application to the vagina or rectum to prevent the transmission of HIV and other sexually transmissible infections (1, 2). While male condoms are known to protect against HIV acquisition (3), oftentimes negotiating their use is difficult for women. Male or female condoms are also unsuitable for women who want to conceive children (2).  To address this need, microbicide research and development began in the 1990s with the aim to develop female-controlled strategies, which could be used discreetly by women, to protect themselves against HIV transmission from their male partners (2).  The concept of rectal microbicides soon followed aimed to protect male, female and transgender people from unprotected rectal anal intercourse (RAI) (4).

The aim of a microbicide is to inactivate or block HIV replication during the early stages of the virus life-cycle to prevent establishment of infection at the mucosa.  Microbicides are designed for use either around coitus (event driven e.g. using a gel before and/or after sex) or independent of coitus such as daily dosing (e.g. gel) or sustained release formulations (e.g. IVR) (2). An advantage of microbicides is the delivery of high concentrations of the active pharmaceutical agent at the site of HIV exposure thereby avoiding significant systemic exposure and potential side effects (2).

While several microbicide candidates have been evaluated in efficacy trials, there are currently no licensed microbicides approved for HIV prevention. There is now a priority for the development and advancement of sustained release microbicides, as well as systemically delivered antiretrovirals (ARV) as pre-exposure prophylaxis (PrEP), that is less reliant on adherence by the user (5).   However, it is recognised within the microbicide field that a diversity of delivery technologies (topical and systemic) is needed to meet the needs and preferences of women from different cultural contexts and throughout their reproductive life-time (6).

Rectal microbicides have been primarily aimed at protecting men who have sex with men (MSM) from HIV acquisition by RAI although they can be used in transgender (7) and heterosexual women engaging in RAI. In the United States, 36% of women 25-44 years of age have reported ever having RAI in their lifetime (8).

 Terminology

 The first-generation microbicides, comprising non-ionic detergents or acids, accurately reflects the terminology (i.e. microbicide) of an agent that directly inactivates microorganisms, including HIV. However, this nomenclature is also extended to topically applied agents containing ARVs (i.e. ARV-based microbicides) that specifically block HIV replication (e.g. the nucleotide reverse transcriptase inhibitor, tenofovir) rather than directly inactivating the virus (2).  A more accurate description to encompass nonspecific and HIV specific microbicides is “Topical Pre-exposure Prophylaxis” (Topical PrEP).  Nevertheless, the term microbicides persists and will be used in this section regardless of the mechanism of action of the active pharmaceutical ingredient formulated for vaginal or rectal delivery via a gel, tablets, capsule, film or ring.