TY - JOUR
T1 - Long-acting implants to treat and prevent HIV infection
AU - Weld, Ethel D.
AU - Flexner, Charles
N1 - Funding Information:
C.F. reports serving as a paid consultant for Cipla Pharmaceuticals, Janssen Pharmaceuticals, Merck Laboratories, Mylan Pharmaceuticals, and ViiV Healthcare, and received research grant support from Gilead Sciences paid to his University. E.W. is an investigator on clinical studies funded by Imquest Biosciences, Inc., GSK/ ViiV, and Navigen Pharmaceuticals, under research contracts managed by Johns Hopkins University.
Funding Information:
C.F. and E.W. received related support during the preparation of this manuscript from NIH grant NIAID R24 AI118397, Long-Acting/Extended Release Antiretroviral Resource Program (LEAP), www.longactinghiv.org, awarded to Johns Hopkins University. E.W. was also supported in this work by the Johns Hopkins University Center for AIDS Research (CFAR) under award number P30AI094189.
Publisher Copyright:
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Purpose of reviewSubcutaneous implants are a promising technology to enable long-acting parenteral delivery of antiretroviral drugs (ARV) because they may be able to provide protective drugs concentrations for a year or longer following a single implant. The present review covers the current status of preclinical and clinical development of antiretroviral implants.Recent findingsOver the past three decades, subcutaneous implants have been widely used for long-acting hormonal contraception and the treatment of hormonally-driven malignancies. They are economical and scalable to manufacture, but require special procedures for insertion and removal. They are generally well tolerated, and can remain in place for up to five years. As long-acting delivery of ARV would confer significant advantages, a few investigational implants are under development for the delivery of ARV; most remain at preclinical stages of development. Islatravir, a potent nucleoside analog reverse transcriptase translocation inhibitor that shows particular promise, has entered clinical testing in implant form. Investigational implants containing tenofovir alafenamide and nevirapine, and entecavir (for hepatitis B virus) have been developed and tested in animal models, with varying degrees of success. There is also burgeoning interest in bioerodable implant formulations of established ARVs.SummaryLARV implants are a promising new technology, but are in early stages of clinical development. Their potential advantages include more consistent and predictable drug release than that provided by intramuscular injections, the possibility of combining several partner drugs into one implant, and the fact that implants can be removed in the case of a desire to stop treatment or the development of adverse events.
AB - Purpose of reviewSubcutaneous implants are a promising technology to enable long-acting parenteral delivery of antiretroviral drugs (ARV) because they may be able to provide protective drugs concentrations for a year or longer following a single implant. The present review covers the current status of preclinical and clinical development of antiretroviral implants.Recent findingsOver the past three decades, subcutaneous implants have been widely used for long-acting hormonal contraception and the treatment of hormonally-driven malignancies. They are economical and scalable to manufacture, but require special procedures for insertion and removal. They are generally well tolerated, and can remain in place for up to five years. As long-acting delivery of ARV would confer significant advantages, a few investigational implants are under development for the delivery of ARV; most remain at preclinical stages of development. Islatravir, a potent nucleoside analog reverse transcriptase translocation inhibitor that shows particular promise, has entered clinical testing in implant form. Investigational implants containing tenofovir alafenamide and nevirapine, and entecavir (for hepatitis B virus) have been developed and tested in animal models, with varying degrees of success. There is also burgeoning interest in bioerodable implant formulations of established ARVs.SummaryLARV implants are a promising new technology, but are in early stages of clinical development. Their potential advantages include more consistent and predictable drug release than that provided by intramuscular injections, the possibility of combining several partner drugs into one implant, and the fact that implants can be removed in the case of a desire to stop treatment or the development of adverse events.
KW - HIV
KW - bioerodable implants
KW - inert polymer implants
KW - long-acting antiretroviral implants
KW - nonbioerodible implants
UR - http://www.scopus.com/inward/record.url?scp=85076125231&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076125231&partnerID=8YFLogxK
U2 - 10.1097/COH.0000000000000591
DO - 10.1097/COH.0000000000000591
M3 - Review article
C2 - 31764198
AN - SCOPUS:85076125231
SN - 1746-630X
VL - 15
SP - 33
EP - 41
JO - Current Opinion in HIV and AIDS
JF - Current Opinion in HIV and AIDS
IS - 1
ER -