TY - JOUR
T1 - Creating demand for long-acting formulations for the treatment and prevention of HIV, tuberculosis, and viral hepatitis
AU - Flexner, Charles
AU - Thomas, David L.
AU - Swindells, Susan
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. S.S. reports research grants to her University from Merck Laboratories and ViiV Healthcare.
Funding Information:
C.F. and S.S. 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. D.L.T. received from NIAID a supplement to a Center for AIDS Research grant 1P30 AI094189, awarded to Johns Hopkins University.
Publisher Copyright:
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Purpose of reviewLong-acting parenteral drug delivery is an established and widely accepted solution to the problem of poor adherence when daily oral medications are used to treat or prevent chronic medical conditions. Poor adherence to oral formulations remains a major barrier to successfully treating or preventing HIV, tuberculosis (TB), and viral hepatitis. The uptake of long-acting formulations developed for these infections is uncertain, despite their promise. This review addresses the current state of development of long-acting and extended-release approaches to HIV, TB, and viral hepatitis in the context of creating market demand for such products.Recent findingsTwo nanoformulated long-acting injectable antiretroviral compounds, cabotegravir and rilpivirine, recently completed Phase 2 clinical trials demonstrating safety, tolerability, and antiretroviral activity, and should be available in high income countries following completion of ongoing Phase 3 trials. Long-acting polymer implants of the antiretroviral nucleosides tenofovir alafenamide and 4'-ethynyl-2-fluoro-2'-deoxyadenosine are being tested in animals and should soon enter human studies; tenofovir alafenamide also has activity against hepatitis B virus. Long-acting versions of several broadly neutralizing monoclonal antibodies are in advanced clinical trials for HIV prevention and treatment. Long-acting formulations for TB are in preclinical development. There is no evidence that comparable formulations for viral hepatitis are being developed at present.SummaryLong-acting and extended release formulations are promising approaches to the treatment and prevention of common infectious diseases, but their availability is limited at this time. These products hold great promise for the global control of important human infections. Based on experience with other diseases, it is likely that their use will become more widespread if they are cost competitive with generic oral formulations.
AB - Purpose of reviewLong-acting parenteral drug delivery is an established and widely accepted solution to the problem of poor adherence when daily oral medications are used to treat or prevent chronic medical conditions. Poor adherence to oral formulations remains a major barrier to successfully treating or preventing HIV, tuberculosis (TB), and viral hepatitis. The uptake of long-acting formulations developed for these infections is uncertain, despite their promise. This review addresses the current state of development of long-acting and extended-release approaches to HIV, TB, and viral hepatitis in the context of creating market demand for such products.Recent findingsTwo nanoformulated long-acting injectable antiretroviral compounds, cabotegravir and rilpivirine, recently completed Phase 2 clinical trials demonstrating safety, tolerability, and antiretroviral activity, and should be available in high income countries following completion of ongoing Phase 3 trials. Long-acting polymer implants of the antiretroviral nucleosides tenofovir alafenamide and 4'-ethynyl-2-fluoro-2'-deoxyadenosine are being tested in animals and should soon enter human studies; tenofovir alafenamide also has activity against hepatitis B virus. Long-acting versions of several broadly neutralizing monoclonal antibodies are in advanced clinical trials for HIV prevention and treatment. Long-acting formulations for TB are in preclinical development. There is no evidence that comparable formulations for viral hepatitis are being developed at present.SummaryLong-acting and extended release formulations are promising approaches to the treatment and prevention of common infectious diseases, but their availability is limited at this time. These products hold great promise for the global control of important human infections. Based on experience with other diseases, it is likely that their use will become more widespread if they are cost competitive with generic oral formulations.
KW - HIV
KW - broadly neutralizing anti-HIV monoclonal antibodies
KW - hepatitis B virus
KW - hepatitis C virus
KW - long-acting antiretroviral drugs
KW - polymer implants
KW - tuberculosis
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U2 - 10.1097/COH.0000000000000510
DO - 10.1097/COH.0000000000000510
M3 - Review article
C2 - 30394948
AN - SCOPUS:85057551095
VL - 14
SP - 13
EP - 20
JO - Current Opinion in HIV and AIDS
JF - Current Opinion in HIV and AIDS
SN - 1746-630X
IS - 1
ER -