*11.2.2.2. Carrageenan*

Carrageenan (Carraguard/R515®) is a sulphonated polysaccharide derived from a seaweed extract, and blocking HIV-1 transmission by binding the HIV-1 envelope. Carrageenan has been found to prevent HIV-1-infected mononuclear cells from migrating across vaginal epithelia to pelvic lymph nodes in mouse models [247]. Phase I safety trials of carraguard gel and similar carageenan-based formulations showed safety in HIV-1 negative men and women [248, 249]. Other clinical trials have shown that carraguard gel was safe in preventing infection by HIV-1 [250, 251]. However, a placebo-controlled phase III study in South Africa, with HIV-1 negative and non-pregnant women, found that although carraguard gel was safe when used over a 2-year period, incident HIV-1 infections occurred at a similar rate in the Carrageenan and placebo groups, with incidence of 3:3 infections per 100 woman-years in the Carrageenan group, and incidence of 3:7 per 100 woman-years in the placebo group, raising major questions about whether poor adherence contributed to the lack of efficacy found in the trial [252].

## *11.2.2.3. Cellulose sulphate and cellulose acetate phthalate*

Cellulose sulphate gel (Ushercell®), acts by binding the V3 loop of the gp120 HIV-1 envelope, and it can inhibit both CXCR4 and CCR5-tropic virus types [253]. Phase III efficacy trials of cellulose sulphate versus placebo showed a higher HIV seroincidence in the trial group [240]. Cellulose acetate phthalate (CAP) is another anionic polymer under investigation as a microbicide agent, that blocks gp120 binding sites, and showed *in vitro* activity against HIV-1 and HSV (types 1 and 2) [255]. CAP has been presented in the form of a film and micronized gel, and has shown ability to block gp120 binding site on CXCR4 and CCR5-tropic virus types [256, 257]. Additionally, the micronised form of CAP provides an acidic environment, which was shown in one study to cause disintegration and loss of infectivity of HIV-1 [258].

#### *11.2.2.4. Dendrimers*

Dendrimers are anionic polymers containing macromolecules, and contain a central core, interior branches, and terminal surface groups adapted to specific targets. Because of their size and multiple terminal surface groups, they possess the ability to bind to multiple locations on multiple cells. O SPL7013 (Vivagel®) is a first dendrimer to be formulated as a microbicide gel and tested clinically. It showed protection from chimeric SHIV in a macaque model, and from HSV2 in two different animal models [259].
