Preventive Efficacy of a Tenofovir Alafenamide Fumarate Nanofluidic Implant in SHIV-Challenged Nonhuman Primates

Fernanda P. Pons-Faudoa; Antons Sizovs; Kathryn A. Shelton; Zoha Momin; Jean A. Niles; Lane R. Bushman; Jiaqiong Xu; Corrine Ying Xuan Chua; Joan E. Nichols; Sandra Demaria; Michael M. Ittmann; Trevor Hawkins; James F. Rooney; Mark A. Marzinke; Jason T. Kimata; Peter L. Anderson; Pramod N. Nehete; Roberto C. Arduino; Mauro Ferrari; K. Jagannadha Sastry; Alessandro Grattoni

doi:https://doi.org/10.1002/adtp.202000163

Preventive Efficacy of a Tenofovir Alafenamide Fumarate Nanofluidic Implant in SHIV-Challenged Nonhuman Primates

Fernanda P. Pons-Faudoa, Antons Sizovs, Kathryn A. Shelton, Zoha Momin, Jean A. Niles, Lane R. Bushman, Jiaqiong Xu, Corrine Ying Xuan Chua, Joan E. Nichols, Sandra Demaria, Michael M. Ittmann, Trevor Hawkins, James F. Rooney, Mark A. Marzinke, Jason T. Kimata, Peter L. Anderson, Pramod N. Nehete, Roberto C. Arduino, Mauro Ferrari, K. Jagannadha SastryAlessandro Grattoni

Research output: Contribution to journal › Article

Abstract

Pre-exposure prophylaxis (PrEP) using antiretroviral oral drugs is effective at preventing human immunodeficiency virus (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 it is shown that LA TAF using a novel subcutaneous nanofluidic implant (nTAF) confers partial protection from HIV transmission. It is demonstrated that sustained subcutaneous delivery through nTAF in rhesus macaques maintains tenofovir diphosphate concentration at a median of 390 fmol per 106 peripheral blood mononuclear cells, nine times above clinically protective levels. In a non-blinded, placebo-controlled rhesus macaque study with repeated low-dose rectal simian HIVSF162P3 (SHIVSF162P3) challenge, the nTAF cohort has a 62.5095 1.72–85.69 p = 0.068) in risk of infection per exposure compared to the control. This finding mirrors that of tenofovir disoproxil fumarate (TDF) monotherapy, where 60 and clinically, 676 this 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.

Original language	English (US)
Pages (from-to)	2000163
Number of pages	1
Journal	advanced therapeutics
Volume	n/a
Issue number	n/a
DOIs	https://doi.org/10.1002/adtp.202000163
State	E-pub ahead of print - Dec 16 2020

Keywords

drug delivery
HIV pre-exposure prophylaxis
implantable devices
nanofluidics
tenofovir alafenamide

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https://onlinelibrary.wiley.com/doi/abs/10.1002/adtp.202000163

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Pons-Faudoa, F. P., Sizovs, A., Shelton, K. A., Momin, Z., Niles, J. A., Bushman, L. R., Xu, J., Chua, C. Y. X., Nichols, J. E., Demaria, S., Ittmann, M. M., Hawkins, T., Rooney, J. F., Marzinke, M. A., Kimata, J. T., Anderson, P. L., Nehete, P. N., Arduino, R. C., Ferrari, M., ... Grattoni, A. (2020). Preventive Efficacy of a Tenofovir Alafenamide Fumarate Nanofluidic Implant in SHIV-Challenged Nonhuman Primates. advanced therapeutics, n/a(n/a), 2000163. https://doi.org/10.1002/adtp.202000163

Preventive Efficacy of a Tenofovir Alafenamide Fumarate Nanofluidic Implant in SHIV-Challenged Nonhuman Primates. / Pons-Faudoa, Fernanda P.; Sizovs, Antons; Shelton, Kathryn A.; Momin, Zoha; Niles, Jean A.; Bushman, Lane R.; Xu, Jiaqiong ; Chua, Corrine Ying Xuan ; Nichols, Joan E.; Demaria, Sandra; Ittmann, Michael M.; Hawkins, Trevor; Rooney, James F.; Marzinke, Mark A.; Kimata, Jason T.; Anderson, Peter L.; Nehete, Pramod N.; Arduino, Roberto C.; Ferrari, Mauro; Sastry, K. Jagannadha; Grattoni, Alessandro.

In: advanced therapeutics, Vol. n/a, No. n/a, 16.12.2020, p. 2000163.

Research output: Contribution to journal › Article

Pons-Faudoa, FP, Sizovs, A, Shelton, KA, Momin, Z, Niles, JA, Bushman, LR, Xu, J , Chua, CYX , Nichols, JE, Demaria, S, Ittmann, MM, Hawkins, T, Rooney, JF, Marzinke, MA, Kimata, JT, Anderson, PL, Nehete, PN, Arduino, RC, Ferrari, M, Sastry, KJ & Grattoni, A 2020, 'Preventive Efficacy of a Tenofovir Alafenamide Fumarate Nanofluidic Implant in SHIV-Challenged Nonhuman Primates', advanced therapeutics, vol. n/a, no. n/a, pp. 2000163. https://doi.org/10.1002/adtp.202000163

Pons-Faudoa, Fernanda P. ; Sizovs, Antons ; Shelton, Kathryn A. ; Momin, Zoha ; Niles, Jean A. ; Bushman, Lane R. ; Xu, Jiaqiong ; Chua, Corrine Ying Xuan ; Nichols, Joan E. ; Demaria, Sandra ; Ittmann, Michael M. ; Hawkins, Trevor ; Rooney, James F. ; Marzinke, Mark A. ; Kimata, Jason T. ; Anderson, Peter L. ; Nehete, Pramod N. ; Arduino, Roberto C. ; Ferrari, Mauro ; Sastry, K. Jagannadha ; Grattoni, Alessandro. / Preventive Efficacy of a Tenofovir Alafenamide Fumarate Nanofluidic Implant in SHIV-Challenged Nonhuman Primates. In: advanced therapeutics. 2020 ; Vol. n/a, No. n/a. pp. 2000163.

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abstract = "Pre-exposure prophylaxis (PrEP) using antiretroviral oral drugs is effective at preventing human immunodeficiency virus (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 it is shown that LA TAF using a novel subcutaneous nanofluidic implant (nTAF) confers partial protection from HIV transmission. It is demonstrated that sustained subcutaneous delivery through nTAF in rhesus macaques maintains tenofovir diphosphate concentration at a median of 390 fmol per 106 peripheral blood mononuclear cells, nine times above clinically protective levels. In a non-blinded, placebo-controlled rhesus macaque study with repeated low-dose rectal simian HIVSF162P3 (SHIVSF162P3) challenge, the nTAF cohort has a 62.5095 1.72–85.69 p = 0.068) in risk of infection per exposure compared to the control. This finding mirrors that of tenofovir disoproxil fumarate (TDF) monotherapy, where 60 and clinically, 676 this 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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AU - Pons-Faudoa, Fernanda P.

AU - Sizovs, Antons

AU - Shelton, Kathryn A.

AU - Momin, Zoha

AU - Niles, Jean A.

AU - Bushman, Lane R.

AU - Xu, Jiaqiong

AU - Chua, Corrine Ying Xuan

AU - Nichols, Joan E.

AU - Demaria, Sandra

AU - Ittmann, Michael M.

AU - Hawkins, Trevor

AU - Rooney, James F.

AU - Marzinke, Mark A.

AU - Kimata, Jason T.

AU - Anderson, Peter L.

AU - Nehete, Pramod N.

AU - Arduino, Roberto C.

AU - Ferrari, Mauro

AU - Sastry, K. Jagannadha

AU - Grattoni, Alessandro

PY - 2020/12/16

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KW - tenofovir alafenamide

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