Microbicides for multidrug-resistant and multitropic HIV-1.
Curr Opin Investig Drugs
; 9(2): 152-69, 2008 Feb.
Article
en En
| MEDLINE
| ID: mdl-18246518
ABSTRACT
The most common mode of acquiring HIV-1 is via sexual transmission across the genital mucosa. Topical microbicides are a promising prevention strategy for the protection against HIV infection and may ultimately have an impact on the global AIDS pandemic. The effectiveness of a microbicide to prevent HIV-1 transmission will depend on the evolutionary and genital transmission dynamics of the viral subtypes, and sexual behavioral characteristics. Contemporary antiretroviral therapy has led to virological failure as a result of HIV-1 reverse transcriptase gene mutations. The transmission of these multidrug-resistant HIV-1 variants, and the superinfection with the same or distinct HIV-1 subtypes and recombination is a formidable hindrance inherent to global microbicide development. Consequently, mechanism-based microbicides targeting both the cell-free and cell-associated HIV-1 variants and subtypes can be expected to have superior clinical efficacy and safety profiles compared with polymeric anionic microbicides. This review describes the discovery of potent anti-HIV-1 agents against multidrug-resistant and multitropic HIV-1 variants with implications for global microbicide development. Stampidine and thiourea non-nucleoside reverse transcriptase inhibitors (NNRTIs) have demonstrated highly potent activity against clinically relevant multidrug-resistant and recombinant HIV-1 isolates spanning different subtypes across several continents. Extensive preclinical studies have shown that stampidine and a candidate thiourea NNRTI (HI-443) have clinical potential as a safe combination microbicide to inhibit, prevent or treat mucosal HIV-1 infections.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
/
VIH-1
/
Antiinfecciosos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Opin Investig Drugs
Asunto de la revista:
TERAPIA POR MEDICAMENTOS
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos