Safety Assessment of Microbicide 2P23 on the Rectal and Vaginal Microbiota and Its Antiviral Activity on HIV Infection

Containment of the AIDS pandemic requires reducing HIV transmission. HIV infection is initiated by the fusion of the membrane between the virus and the cell membrane of the host. 2P23 is an effective HIV membrane fusion inhibitor that may be a good entry inhibitor microbicide candidate. This study evaluated the potential of using gel-formulated 2P23 as a topical microbicide to prevent sexual transmission of HIV in the rectum and vagina. Our data revealed that 2P23 formulated in gel is effective against HIV. There was no change in antiviral activity at 25°C for 4 months or 60°C for 1 week. In addition, we demonstrated that the 2P23 gel was stable and fully functional at pH 4.0–8.0 and under different concentrations of H2O2. Finally, the 2P23 gel exhibited no cytotoxicity or antimicrobial activity and did not induce inflammatory changes in the rectal or vaginal mucosal epithelium in New Zealand rabbits after 20 mg/day daily rectovaginal application for 14 consecutive days. Despite repeated tissue sampling and 2P23 gel treatment, the inflammatory cytokines and microbiota of the rectum and vagina remained stable. These results add to general knowledge on the in vivo evaluation of anti-HIV microbicide application concerning inflammatory cytokines and microbiota changes in the rectum and vagina. These findings suggest that the 2P23 gel is an excellent candidate for further development as a safe and effective pre-exposure prophylactic microbicide for the prevention of HIV transmission.

Lactoferrin nanoparticles coencapsulated with curcumin and tenofovir improve vaginal defense against HIV-1 infection

Aim: We report here the development of tenofovir- and curcumin-loaded lactoferrin nanoparticles (TCNPs) as an HIV-microbicide. Materials & methods: TCNPs were subjected to various physicochemical characterization experiments, followed by in vitro and in vivo experiments to assess their efficacy. Results: TCNPs had a diameter of 74.31 ± 2.56 nm with a gross encapsulation of more than 61% for each drug. Nanoparticles were effective against HIV-1 replication, with an IC50 of 1.75 μM for curcumin and 2.8 μM for tenofovir. TCNPs provided drug release at the application site for up to 8–12 h, with minimal leakage into the systemic circulation. TCNPs showed spermicidal activity at ≥200 μM and induced minimal cytotoxicity and inflammation in the vaginal epithelium as revealed by histopathological and ELISA studies. Conclusion: We demonstrated that TCNPs could serve as a novel anti-HIV microbicidal agent in rats. [Formula: see text]

The Future of HIV Prevention: Prospects for an Effective Anti-HIV Microbicide

As the devastation of the HIV-AIDS epidemic continues, women are increasinglybearing the greatest impact, particularly in developing countries[1]. In many of these countries, nearly 60% of people living with HIVAIDSare women [2], and in several African countries, women 15 to 24 yearsof age are more than three times more likely to be infected than men thesame age [3]. In South Africa, one in four women is infected by 22 yearsof age [4]. Globally, more than 17.5 million women are now living withHIV-AIDS [5], and there are an estimated 13.2 million infected women insub-Saharan Africa [6].Although effective prevention technologies and strategies do alreadyexist, these are clearly insufficient to address the problems of the epidemic,especially in developing countries. The ‘‘ABC’’ approach (Abstinence, Befaithful, and use Condoms) has been used with some success in a numberof African countries [5,7]. However, in a survey among young women in

Impact of Q-Griffithsin anti-HIV microbicide gel in non-human primates: In situ analyses of epithelial and immune cell markers in rectal mucosa

Natural-product derived lectins can function as potent viral inhibitors with minimal toxicity as shown in vitro and in small animal models. We here assessed the effect of rectal application of an anti-HIV lectin-based microbicide Q-Griffithsin (Q-GRFT) in rectal tissue samples from rhesus macaques. E-cadherin+ cells, CD4+ cells and total mucosal cells were assessed using in situ staining combined with a novel customized digital image analysis platform. Variations in cell numbers between baseline, placebo and Q-GRFT treated samples were analyzed using random intercept linear mixed effect models. The frequencies of rectal E-cadherin+ cells remained stable despite multiple tissue samplings and Q-GRFT gel (0.1%, 0.3% and 1%, respectively) treatment. Whereas single dose application of Q-GRFT did not affect the frequencies of rectal CD4+ cells, multi-dose Q-GRFT caused a small, but significant increase of the frequencies of intra-epithelial CD4+ cells (placebo: median 4%; 1% Q-GRFT: median 7%) and of the CD4+ lamina propria cells (placebo: median 30%; 0.1–1% Q-GRFT: median 36–39%). The resting time between sampling points were further associated with minor changes in the total and CD4+ rectal mucosal cell levels. The results add to general knowledge of in vivo evaluation of anti-HIV microbicide application concerning cellular effects in rectal mucosa.

Griffithsin, a Highly Potent Broad-Spectrum Antiviral Lectin from Red Algae: From Discovery to Clinical Application

Keywords: griffithsin (GRFT); lectin; carbohydrate-binding; human immunodeficiency virus (HIV); microbicide; virus entry inhibitor