Development of dapivirine vaginal ring for HIV prevention

Devlin, Bríd; Nuttall, Jeremy; Wilder, Susan Z.; Woodsong, Cynthia; Rosenberg, Zeda F.

doi:10.1016/j.antiviral.2013.09.025

Cited by 72 publications

(52 citation statements)

References 34 publications

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“…Despite these 567 apparent high values, dapivirine is highly potent and presents 568 selectivity index values considered suitable for microbicide devel-569 opment [56]. Potential safety issues have also been ruled out in 570 clinical trials lasting up to several weeks and testing different dapi-571 virine-based products intended for daily or continuous use [58,59]. 572 Cell viability for drug-free NPs was above 70-80% (CC 50 > 300 lM) NPs can dramatically change their cytotoxic profiles [11,12].…”

mentioning

confidence: 97%

“…This strategy, also commonly referred to as topical pre- 54 exposure prophylaxis (PrEP), comprises the use of vaginal products 55 containing anti-HIV compounds prior to or around the time of sex- 56 ual intercourse in order to avoid early transmission events at the 57 mucosal level [1]. Proof-of-concept for vaginal microbicides was 58 recently achieved in a Phase 2b clinical trial testing a gel contain- 59 ing 1% of the nucleotide reverse transcriptase inhibitor (NtRTI) 60 tenofovir [2]. Most microbicide products developed and tested so 61 far in human clinical trials have relied in semi-solid dosage forms, 62 particularly gels.…”

mentioning

confidence: 99%

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Precise engineering of dapivirine-loaded nanoparticles for the development of anti-HIV vaginal microbicides

Neves

Sarmento

2015

Acta Biomaterialia

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confidence: 97%

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confidence: 99%

Precise engineering of dapivirine-loaded nanoparticles for the development of anti-HIV vaginal microbicides

Neves

Sarmento

2015

Acta Biomaterialia

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“…18 The most advanced candidate is a dapivirine intravaginal ring that is currently being evaluated in two Phase 3 studies (IPM-027 and MTN-020). 19 The ring platform also has the potential to deliver multiple products including antiretroviral and contraceptive agents that might increase product acceptability in communities where antiretroviral PrEP is stigmatized, whereas contraception is not.…”

Section: Intravaginal Ringsmentioning

confidence: 99%

An Overview of Antiretroviral Pre‐Exposure Prophylaxis of HIV Infection

McGowan

2014

American J Rep Immunol

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Despite improvements in access to antiretroviral therapy and the use of simplified dosing regimens, HIV infection is still an important global public health problem. As a consequence, significant research efforts have been focused on the development of strategies to prevent the acquisition of HIV infection. These efforts have begun to produce results. The HPTN‐052 study demonstrated the effectiveness of treating infected individuals as a means to prevent onward transmission of HIV infection. In addition, Phase 2B/3 studies have shown that the use of oral and topical antiretroviral pre‐exposure prophylaxis (PrEP) can significantly reduce the acquisition of HIV infection in serodiscordant couples, young women in sub‐Saharan Africa, men who have sex with men, and intravenous drug users. Despite these successes, challenges remain. Adherence to daily PrEP is variable, and some large studies have failed to demonstrate the effectiveness of PrEP in reducing HIV acquisition. Novel PrEP technologies, including sustained delivery intravaginal rings and long‐acting injectable products, are being developed to try and circumvent adherence problems associated with daily PrEP regimens. The purpose of this article is to briefly summarize recent progress in the development of antiretroviral PrEP.

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“…Nevirapine is an important agent for the prevention of mother-to-child transmission of HIV infection [6]. UC781, MIV-150, and dapivirine have all been evaluated in gel or intravaginal ring formulations [7][8][9]. Initial studies in rats and dogs established an optimal 200 nm nanosuspension formulation with 300 mg of TMC278 per milliliter of the final formulation [10,11].…”

Section: Preclinical Developmentmentioning

confidence: 98%