*11.2.3. Detergents or surfactants*

237]. Naphthalene sulphonate [238], carrageenan [239], cellulose sulphate [240], cellulose acetate phthalate [241], and dendrimers [242], are the main compounds evaluated in clinical

Naphthalene sulphonate (PRO2000® gel), is a sulphfonated polymer with *in vitro* activity against HIV-1, *C. trachomatis*, *N. gonorrhoeae*, and HSV [243, 244]. Phase I clinical trials have shown that naphthalene sulphonate gel was generally well tolerated [238, 245]. Phase ll/llb revealed safety and efficacy, and a phase III efficacy trial, show that the naphthalene sulpho‐ nate gel has better efficacy when compared with BufferGel, gel placebo, or the condom [238,

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].

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].

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

trials, phase l, ll and lll (Table 6)*.*

154 Trends in Basic and Therapeutic Options in HIV Infection - Towards a Functional Cure

*11.2.2.3. Cellulose sulphate and cellulose acetate phthalate*

*11.2.2.1. Naphthalene sulphonate*

244, 246].

*11.2.2.2. Carrageenan*

*11.2.2.4. Dendrimers*

Detergents or Surfactants were the first compounds evaluated clinically as topical microbi‐ cides. These topical agents act in a nonspecific way disrupt membranes, offering contraceptive properties and activity against a wide range of potential STI pathogens [260, 261]. The agents of this class of topical Microbicides are represented by nonoxynol 9 (N-9), C31G, and sodium lauryl sulfate (SLS) (Table 6).
