RESUMO
Vaginal inserts that can be used on demand before or after sex may be a desirable human immunodeficiency virus (HIV) prevention option for women. We recently showed that inserts containing tenofovir alafenamide fumarate (TAF, 20â mg) and elvitegravir (EVG, 16â mg) were highly protective against repeated simian/human immunodeficiency virus (SHIV) vaginal exposures when administered to macaques 4 hours before or after virus exposure (93% and 100%, respectively). Here, we show in the same macaque model that insert application 8 hours or 24 hours after exposure maintains high efficacy (94.4% and 77.2%, respectively). These data extend the protective window by TAF/EVG inserts and inform their clinical development for on-demand prophylaxis in women.
Assuntos
Adenina , Alanina , Fármacos Anti-HIV , Quinolonas , Síndrome de Imunodeficiência Adquirida dos Símios , Tenofovir , Animais , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , Feminino , Quinolonas/administração & dosagem , Quinolonas/farmacologia , Alanina/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Fármacos Anti-HIV/administração & dosagem , Adenina/análogos & derivados , Adenina/administração & dosagem , Adenina/farmacologia , Adenina/uso terapêutico , Vagina/virologia , Vagina/efeitos dos fármacos , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Administração Intravaginal , Macaca mulatta , Modelos Animais de DoençasRESUMO
HIV/AIDS remains a global public health issue, and products available for the prevention of HIV infections are limited, especially those for short-acting, on-demand, user-controlled applications. Topical inserts are products that can be applied vaginally or rectally and have been explored as drug delivery systems. To fill the gap in the HIV prevention product pipeline, CONRAD has developed a topical insert containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG), two potent and synergistic antiretrovirals, as a simple, low-cost, and discreet option that can be self-administered vaginally and/or rectally, before and after coitus. In this review, we have described the development path of the TAF/EVG insert up to its current point in clinical testing, highlighting findings from acceptability, preclinical safety, pharmacokinetics, and efficacy evaluations and early clinical studies. In summary, the TAF/EVG inserts are stable, easy to manufacture, low-cost, acceptable, and show highly promising preclinical and clinical results for on-demand topical pre- or post-exposure HIV prevention.