Preventive efficacy of a tenofovir alafenamide fumarate nanofluidic implant in SHIV-challenged nonhuman primates

Pons-Faudoa, F. P.; Sizovs, A.; Shelton, K. A.; Momin, Z.; Bushman, L. R.; Chua, C. Y. X.; Nichols, J. E.; Hawkins, T.; Rooney, J. F.; Marzinke, M. A.; Kimata, J. T.; Anderson, P. L.; Nehete, P. N.; Arduino, R. C.; Ferrari, M.; Sastry, K. J.; Grattoni, A.

doi:10.1101/2020.05.13.091694

bioRxiv · 10.1101/2020.05.13.091694

Preventive efficacy of a tenofovir alafenamide fumarate nanofluidic implant in SHIV-challenged nonhuman primates

Pons-Faudoa, F. P.·Sizovs, A.·Shelton, K. A.·Momin, Z.·Bushman, L. R.·Chua, C. Y. X.·Nichols, J. E.·Hawkins, T.·Rooney, J. F.·Marzinke, M. A.·Kimata, J. T.·Anderson, P. L.·Nehete, P. N.·Arduino, R. C.·Ferrari, M.·Sastry, K. J.·Grattoni, A.

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Abstract

Pre-exposure prophylaxis (PrEP) using antiretroviral oral drugs is effective at preventing HIV transmission when individuals adhere to the dosing regimen. Tenofovir alafenamide (TAF) is a potent antiretroviral drug, with numerous long-acting (LA) delivery systems under development to improve PrEP adherence. However, none has undergone preventive efficacy assessment. Here we show that LA TAF using a novel subcutaneous nanofluidic implant (nTAF) confers partial protection from HIV transmission. We demonstrate that sustained subcutaneous delivery through nTAF in rhesus macaques maintained tenofovir diphosphate concentration at a median of 390.00 fmol/106 peripheral blood mononuclear cells, 9 times above clinically protective levels. In a non-blinded, placebo-controlled rhesus macaque study with repeated low-dose rectal SHIVSF162P3 challenge, the nTAF cohort had a 62.50% reduction (95% CI: 1.72% to 85.69%; p=0.068) in risk of infection per exposure compared to the control. Our finding mirrors that of tenofovir disoproxil fumarate (TDF) monotherapy, where 60.00% protective efficacy was observed in macaques, and clinically, 67.00% reduction in risk with 86.00% preventive efficacy in individuals with detectable drug in the plasma. Overall, our nanofluidic technology shows potential as a subcutaneous delivery platform for long-term PrEP and provides insights for clinical implementation of LA TAF for HIV prevention.

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Pons-Faudoa, F. P., Sizovs, A., Shelton, K. A., Momin, Z., Bushman, L. R., Chua, C. Y. X., Nichols, J. E., Hawkins, T., Rooney, J. F., Marzinke, M. A., Kimata, J. T., Anderson, P. L., Nehete, P. N., Arduino, R. C., Ferrari, M., Sastry, K. J., Grattoni, A.. 2020-05-17. Preventive efficacy of a tenofovir alafenamide fumarate nanofluidic implant in SHIV-challenged nonhuman primates. https://doi.org/10.1101/2020.05.13.091694

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