| Title: |
Long-acting refillable nanofluidic implant confers protection against SHIV infection in nonhuman primates. |
| Authors: |
Pons-Faudoa, Fernanda P.; Di Trani, Nicola; Capuani, Simone; Campa-Carranza, Jocelyn Nikita; Nehete, Bharti; Sharma, Suman; Shelton, Kathryn A.; Bushman, Lane R.; Abdelmawla, Farah; Williams, Martin; Roon, Laura; Nerguizian, David; Chua, Corrine Ying Xuan; Ittmann, Michael M.; Nichols, Joan E.; Kimata, Jason T.; Anderson, Peter L.; Nehete, Pramod N.; Arduino, Roberto C.; Grattoni, Alessandro |
| Source: |
Science Translational Medicine; 6/28/2023, Vol. 15 Issue 702, p1-14, 14p |
| Abstract: |
The impact of pre-exposure prophylaxis (PrEP) on slowing the global HIV epidemic hinges on effective drugs and delivery platforms. Oral drug regimens are the pillar of HIV PrEP, but variable adherence has spurred development of long-acting delivery systems with the aim of increasing PrEP access, uptake, and persistence. We have developed a long-acting subcutaneous nanofluidic implant that can be refilled transcutaneously for sustained release of the HIV drug islatravir, a nucleoside reverse transcriptase translocation inhibitor that is used for HIV PrEP. In rhesus macaques, the islatravir-eluting implants achieved constant concentrations of islatravir in plasma (median 3.14 nM) and islatravir triphosphate in peripheral blood mononuclear cells (median 0.16 picomole per 106 cells) for more than 20 months. These drug concentrations were above the established PrEP protection threshold. In two unblinded, placebo-controlled studies, islatravir-eluting implants conferred 100% protection against infection with SHIVSF162P3 after repeated low-dose rectal or vaginal challenge in male or female rhesus macaques, respectively, compared to placebo control groups. The islatravir-eluting implants were well tolerated with mild local tissue inflammation and no signs of systemic toxicity over the 20-month study period. This refillable islatravir-eluting implant has potential as a long-acting drug delivery system for HIV PrEP. Editor's summary: Pons-Faudoa and colleagues developed a microfluidic implant inserted under the skin for sustained delivery of the antiretroviral drug islatravir in rhesus macaques. The implant maintained a preventative concentration of islatravir in the blood and tissues of nonhuman primates for 20 months. The implant protected the animals against vaginal or rectal challenge with SHIV. The authors showed that the implant was well-tolerated in nonhuman primates. This delivery technology shows promise for improving adherence to prophylactic drugs for HIV prevention. —Orla Smith [ABSTRACT FROM AUTHOR] |
| : |
Copyright of Science Translational Medicine is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |