Enzyme Responsive Vaginal Microbicide Gels Containing Maraviroc and Tenofovir Microspheres Designed for Acid Phosphatase-Triggered Release for Pre-Exposure Prophylaxis of HIV-1: A Comparative Analysis of a Bigel and Thermosensitive Gel

The challenges encountered with conventional microbicide gels has necessitated the quest for alternative options. This study aimed to formulate and evaluate a bigel and thermosensitive gel, designed to combat the challenges of leakage and short-residence time in the vagina. Ionic-gelation technique was used to formulate maraviroc and tenofovir microspheres. The microspheres were incorporated into a thermosensitive gel and bigel, then evaluated. Enzyme degradation assay was used to assess the effect of the acid phosphatase enzyme on the release profile of maraviroc and tenofovir microspheres. HIV efficacy and cytotoxicity of the microspheres were assessed using HIV-1-BaL virus strain and HeLa cell lines, respectively. Maraviroc and tenofovir release kinetics followed zero-order and Higuchi model kinetics. However, under the influence of the enzyme, maraviroc release was governed by first-order model, while tenofovir followed a super case II transport-mechanism. The altered mode of release and drug transport mechanism suggests a triggered release. The assay of the microspheres suspension on the HeLa cells did not show signs of cytotoxicity. The thermosensitive gel and bigel elicited a progressive decline in HIV infectivity, until at concentrations of 1 μg/mL and 0.1 μg/mL, respectively. The candidate vaginal gels have the potential for a triggered release by the acid phosphatase enzyme present in the seminal fluid, thus, serving as a strategic point to prevent HIV transmission.

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.