Multipurpose Prevention Approaches with Antiretroviral-Based Formulations

Area of Science:

• Virology
• Pharmacology
• Preclinical Research

Background:

• Antiretroviral microbicides are crucial for HIV prevention.
• Tenofovir (TFV) 1% gel is a studied topical microbicide.
• MZC gel, containing MIV-150, zinc, and carrageenan, is a novel candidate.

Purpose of the Study:

• To compare the preclinical safety and efficacy of TFV 1% gel and MZC gel.
• To evaluate antiviral activity against simian-human immunodeficiency virus (SHIV) and herpes simplex virus 2 (HSV-2).

Main Methods:

• Conducted in vitro, ex vivo, and in vivo assays.
• Assessed antiviral therapeutic indexes (TI) using 50% cytotoxic concentration/50% effective concentration ratios.
• Evaluated anti-SHIV reverse transcriptase (SHIV-RT) activity in rhesus macaque vaginal explants.
• Tested protection against vaginal HSV-2 challenge in mice.

Main Results:

• Both gels exhibited good antiviral therapeutic indexes (TI > 25).
• MZC gel demonstrated significantly greater anti-SHIV-RT activity than TFV 1% gel in ex vivo assays.
• MZC gel provided significant protection against vaginal HSV-2 challenge in mice (P < 0.0001), whereas TFV 1% gel did not.

Conclusions:

• MZC gel exhibits superior preclinical efficacy compared to TFV 1% gel for topical microbicide applications.
• MZC gel's potent antiviral activity warrants further investigation for HIV and HSV-2 prevention.
• The combination of MIV-150, zinc, and carrageenan in MZC gel shows promising results.