In search of the optimal delivery method for anti-HIV microbicides: are intravaginal rings the way forward?

نویسندگان

  • Nina Derby
  • Thomas Zydowsky
  • Melissa Robbiani
چکیده

© 2013 Expert Reviews Ltd Intravaginal rings are an advantageous microbicide delivery platform Microbicides are urgently needed to help stem the HIV epidemic [1]. With time and resources at a premium, donors, researchers and regulators agree that only the most promising candidates should be pursued (although they do not always agree on how to prioritize them) [2]. Following the realization that microbicides comprising nonspecific inhibitors were not effective [3], the field has focused principally on topical gels and oral pre-exposure prophylaxis containing antiretroviral drugs, especially reverse transcriptase inhibitors (RTIs). Significant protection was achieved in clinical trials of a pericoital 1% tenofovir (TFV) gel (CAPRISA 004) [1] and a pill of Truvada once daily (iPrex) [4], positioning microbicides solidly in the fight against HIV. Nevertheless, the best correlate of microbicide efficacy is drug concentration at the exposure site [5,6]. Low adherence to gel regimens results in sub-therapeutic drug levels in the mucosa [1,5], and oral dosing achieves substantially lower vaginal levels than vaginally applied agents [7]. These factors probably contributed to the failure of the VOICE (topical 1% TFV gel) and FEM-PrEP (oral Truvada) trials [7], and indicate that other HIV prevention strategies are still needed. Intravaginal rings (IVRs) provide an alternative delivery method for topical microbicides. Widely used for contraception and hormone replacement therapy [8], IVRs offer sustained release of active pharmaceutical ingredients (APIs), having the potential for long-acting protection [2,8]. Used discretely, independent of coitus and requiring minimal effort after insertion, IVRs have been accepted by users [9] and may improve adherence over gels [9,10]. Moreover, recent macaque data show that IVRs releasing the nonnucleoside RTI (NNRTI) MIV-150 offer significant protection against HIV reverse transcriptase in a simian immunodeficiency virus background (SHIV-RT) [11], demonstrating the promise of IVRs for reducing HIV transmission.

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عنوان ژورنال:
  • Expert review of anti-infective therapy

دوره 11 1  شماره 

صفحات  -

تاریخ انتشار 2013