The Efficacy and Safety of Topical Microbicide Gels to Prevent Sexual Transmission of Human Immunodeficiency Virus (HIV) Infection: a Systematic Review and Meta-analysis

Background: Topical microbicide gels are a potential method to reduce sexually transmitted human immunodeficiency virus (HIV) infection, especially in women. Several randomized controlled trials (RCTs) of topical microbicides to prevent HIV transmission have yielded promising results, however trial results have been inconsistent. The objective of this study was to determine the efficacy and safety of topical microbicide gels to prevent HIV transmission.Methods: We conducted meta-analyses, stratified by microbicide gel type, using a random-effects model. We included 25 RCTs that met the inclusion criteria: 13 RCTs examined gel efficacy during heterosexual contact, and an additional 12 trials reported on gel acceptability, participants’ adherence to intervention, and adverse reactions (allergic reaction and pain). Results: With this limited data, topical microbicide gels were not found to be significantly better than placebo in preventing HIV infection (risk ratio (RR) 0.93, 95% CI 0.82 to 1.04; I2 14%; 13 trials; 31,764 participants). It should be noted that low adherence rates were frequently reported within trials. In one trial with high participant adherence (>70%) to intervention, there was a significant protective effect of gels (RR 0.63, 95% CI 0.43 to 0.93; 889 participants). While measures of acceptability and adherence to intervention were similar between groups, administration of topical microbicides were associated with an increased incidence of pain at the application site (RR 1.16, 95% CI 1.00 to 1.36, I2 0%, 15 trials, 19,554 participants).Conclusions: In conclusion, efficacy of topical microbicide gels may relate to baseline risk and compliance with the intervention. In the general population it is not associated with protection from sexually transmitted HIV infection.

High Preventive Effect of G2-S16 Anionic Carbosilane Dendrimer against Sexually Transmitted HSV-2 Infection

Anionic carbosilane dendrimers such as G2-S16 are very effective in preventing HSV-2 infection both in vitro and in vivo. We present the main achievements obtained for the G2-S16 dendrimer in vivo, especially related to its efficacy against HSV-2 infection. Moreover, we discuss the mechanisms by which the G2-S16 dendrimer applied vaginally as a topical microbicide has been demonstrated to be safe and harmless for the vaginal microbiome balance, as both conditions present an essential step that has to be overcome during microbicide development. This review points to the marked protective effect of the G2-S16 dendrimer against sexually transmitted HSV-2 infection, supporting its role as a possible microbicide against HSV-2 infection.

The Agmatine-Containing Poly(Amidoamine) Polymer AGMA1 Binds Cell Surface Heparan Sulfates and Prevents Attachment of Mucosal Human Papillomaviruses

ABSTRACTThe agmatine-containing poly(amidoamine) polymer AGMA1 was recently shown to inhibit the infectivity of several viruses, including human papillomavirus 16 (HPV-16), that exploit cell surface heparan sulfate proteoglycans (HSPGs) as attachment receptors. The aim of this work was to assess the antiviral activity of AGMA1 and its spectrum of activity against a panel of low-risk and high-risk HPVs and to elucidate its mechanism of action. AGMA1 was found to be a potent inhibitor of mucosal HPV types (i.e., types 16, 31, 45, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 0.34 μg/ml and 0.73 μg/ml, and no evidence of cytotoxicity was observed. AGMA1 interacted with immobilized heparin and with cellular heparan sulfates, exerting its antiviral action by preventing virus attachment to the cell surface. The findings from this study indicate that AGMA1 is a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections.