**7. Microbicides as preventive/treatment options**

Microbicides are applications applied inside the vagina or rectum that protects against sexually transmitted infections (STIs) including HIV. These types of chemical applications could be formulated as gels, creams, films, or suppositories. Microbicides are potential HIV prevention options which can reduce the spread of HIV especially among women in developing countries. Without a preventive HIV vaccine, microbicides [116] offer an alternative to condoms as the most feasible method for primary prevention of HIV. Microbicides- intravaginal/intrarectal topical formulations of anti-HIV agents have also been proposed to prevent HIV transmission. Currently, antiretroviral-based microbicides have been achieved for the prevention of HIV new infections among women after many years of failed trial. More than 60 candidate agents have been identified to have *in vitro* activity against HIV, several of which have advanced to clinical testing stage.

At least 10 reverse transcriptase inhibitors and 16 entry inhibitors have been or are in the process of being investigated in clinical or preclinical trials. Ideally, these compounds are characterized by high potency, low absorption from the vagina to the blood to minimize development of resistance, and have a long half-life in order to remain active over a long period. Tenofovir has also been formulated as a topical vaginally applied gel and assessed for its protective effect against Simian immunodeficiency virus (SIV) in macaques. The results indicated that the macaques receiving the tenofovir gel were completely protected from infection [117] and in human trials [118]. The results of the human trial were released in July 2010 and showed that use of the gel reduced acquisition of HIV infection by 39% overall, and by 54% in women who were highly adherent to gel use [118].

Topical microbicides are grouped into five classes of agents, based on their mode and site of action [119] (Table 3)


**Table 3.** Microbicides and their mechanism of action

For development of acceptable microbicide, researchers must develop not only the active ingredient but also a socially acceptable, affordable, and easy to apply microbicide providing protection for several days and/or weeks. Other major issues include how a microbicide might affect sperm and the possibility of causing adverse effects in women reproductive health. In Table 3 the listed microbicides failed to achieve the desired results except for tenofovir gel which showed 39% less likelihood for users to become infected with HIV than women who received a placebo gel. For women who adhered to tenofovir gel prescription correctly, HIV infection was 54% less likely than the placebo group.
