Review
Infectious Diseases
Stefano Rusconi, Maria M. Santoro, Amedeo F. Capetti, Nicola Gianotti, Maurizio Zazzi
Summary: HIV infection is now treated as a chronic disease thanks to advancements in antiretroviral therapy. Switching to new treatment regimens is common during long-term therapy to avoid complications and drug resistance. The approval of long-acting injectable drugs containing cabotegravir and rilpivirine has demonstrated high efficacy and safety, representing a significant achievement in the field of HIV treatment.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Critical Care Medicine
Ching -Fu Weng, Chien-Chih Wu, Mei-Hsuan Wu, Fang-Ju Lin
Summary: This retrospective cohort study compared the differences in acute exacerbation (AE) and cardiovascular events among patients with COPD receiving different LAMA/LABA fixed-dose combinations (FDCs). The results showed that patients treated with UMEC/VI or GLY/IND had a lower risk of severe AE compared to those receiving TIO/OLO. Additionally, GLY/IND users tended to have a lower risk of cardiovascular events compared to TIO/OLO users.
Review
Pharmacology & Pharmacy
Lalitkumar K. Vora, Akmal H. Sabri, Yara Naser, Achmad Himawan, Aaron R. J. Hutton, Qonita Kurnia Anjani, Fabiana Volpe-Zanutto, Deepakkumar Mishra, Mingshan Li, Aoife M. Rodgers, Alejandro J. Paredes, Eneko Larran, Raghu Raj Singh Thakur, Ryan F. Donnelly
Summary: The minimally-invasive and painless nature of microneedle (MN) application has enabled the technology to obviate many issues with injectable drug delivery. MNs not only administer therapeutics directly into the dermal and ocular space, but they can also control the release profile of the active compound over a desired period. This review discusses various MN formulations loaded with different therapeutics, the design aspects such as polymer selection and MN geometry, as well as manufacturing and regulatory hurdles that need to be overcome to bring MN technology to the market.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Mohammad Ullah Nayan, Brady Sillman, Mahmudul Hasan, Suyash Deodhar, Srijanee Das, Ashrafi Sultana, Nam Thai Hoang Le, Vicente Soriano, Benson Edagwa, Howard E. Gendelman
Summary: Adherence to daily ART is a barrier in HIV treatment and prevention. Long-acting ARVs and other formulations are now in use or in development to simplify treatment regimens. However, challenges remain in dosing intervals, administration, and access. Future developments in ultra-long-acting ARTs may offer improved treatment options.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Article
Infectious Diseases
Charles Flexner, Andrew Owen, Marco Siccardi, Susan Swindells
Summary: Long-acting and extended-release formulations are crucial for improving the treatment and prevention of chronic HIV infection. Strategies to manage toxicity, resistance, and falling drug concentrations are important considerations, with integrase inhibitors and broadly-neutralising monoclonal antibodies showing promising efficacy.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Article
Multidisciplinary Sciences
Manjula Gunawardana, Mariana Remedios-Chan, Debbie Sanchez, Simon Webster, Amalia E. Castonguay, Paul Webster, Christopher Buser, John A. Moss, MyMy Trinh, Martin Beliveau, Craig W. Hendrix, Mark A. Marzinke, Michael Tuck, Richard M. Caprioli, Michelle L. Reyzer, Joseph Kuo, Philippe A. Gallay, Marc M. Baum
Summary: Global efforts to prevent HIV-1 infection in vulnerable populations are stagnant, while the development of long-acting subdermal implants delivering the potent prodrug, TAF, shows significant potential. In this study, using mouse models and imaging mass spectrometry, we address knowledge gaps in the preclinical pharmacology of long-acting subdermal TAF delivery and determine the effective TAF dose for preventing HIV-1 acquisition.
SCIENTIFIC REPORTS
(2022)
Article
Respiratory System
Masato Muraki, Yuki Kunita, Ken Shirahase, Ryo Yamazaki, Soichiro Hanada, Hirochiyo Sawaguchi, Yuji Tohda
Summary: The study compared the effectiveness, preference, and safety of three LAMA/LABA FDCs in patients with COPD, showing similar effects and safety among the three treatments, with no significant differences reported in most patient preferences.
BMC PULMONARY MEDICINE
(2021)
Review
Nanoscience & Nanotechnology
Wei Li, Jie Tang, Dennis Lee, Thomas R. Tice, Steven P. Schwendeman, Mark R. Prausnitz
Summary: Long-acting drug delivery formulations enable sustained and prolonged drug release, improving patient compliance. This review discusses FDA-approved long-acting drug delivery formulations, including different slow-release mechanisms and materials, and provides a comprehensive summary of their clinical applications and product information.
NATURE REVIEWS MATERIALS
(2022)
Review
Immunology
Jordan E. Lake, Janine Trevillyan
Summary: Obesity is on the rise in people with HIV, with integrase inhibitors and tenofovir alafenamide being associated with weight gain. Understanding the mechanisms of how antiretroviral therapies lead to weight gain is crucial for informed treatment decisions, as this weight gain can result in significant medical complications for PWH.
CURRENT OPINION IN HIV AND AIDS
(2021)
Article
Microbiology
Kirsten L. White, Nathan Osman, Ernesto Cuadra-Foy, Bluma G. Brenner, Devleena Shivakumar, Federico Campigotto, Manuel Tsiang, Philip A. Morganelli, Nikolai Novikov, Scott E. Lazerwith, Haolun Jin, Anita Niedziela-Majka
Summary: The HIV integrase strand transfer inhibitor bictegravir has a longer dissociation half-life and more durable antiviral activity against wild-type HIV compared to other drugs like dolutegravir, raltegravir, and elvitegravir. Bictegravir makes more contacts with the IN-DNA complex than dolutegravir, contributing to its prolonged residence time and resilience against many resistance mutations.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Critical Care Medicine
Meng-Ting Wang, Jyun-Heng Lai, Ya-Ling Huang, Jun-Ting Liou, Shih-Hsuan Cheng, Chen Wei Lin, Hsueh-Yi Pan, Yu-Juei Hsu, Chen-Liang Tsai
Summary: In this study, the comparative effectiveness and safety of LABA/LAMA and LABA/ICS FDCs in COPD patients were investigated using Taiwanese nationwide health care claims. Indacaterol plus glycopyrronium (IND/GLY) and vilanterol plus umeclidinium (VI/UMEC) were found to be associated with lower exacerbation rates and pneumonia risks compared to salmeterol plus fluticasone propionate (SAL/FP). However, no significant differences were observed between LABA/LAMA FDCs.
Article
Virology
Alberto Borghetti, Damiano Farinacci, Arturo Ciccullo, Alex Dusina, Davide Moschese, Valentina Iannone, Anna D'Angelillo, Francesca Lombardi, Valentina Delle Donne, Valentina Massaroni, Elena Visconti, Enrica Tamburrini, Simona Di Giambenedetto
Summary: This study examined the eligibility criteria for HIV-positive patients to switch to injectable therapy using cabotegravir and rilpivirine. The results showed a considerable proportion of patients did not meet the eligibility criteria, mainly due to virological failures, resistance mutations, etc. Additionally, fertile women were excluded due to the lack of data on this combination during pregnancy and breastfeeding.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Denise A. Cobb, Nathan Smith, Suyash Deodhar, Aditya N. Bade, Nagsen Gautam, Bhagya Laxmi Dyavar Shetty, JoEllyn McMillan, Yazen Alnouti, Samuel M. Cohen, Howard E. Gendelman, Benson Edagwa
Summary: This study reports on two lipophilic tenofovir ProTide nanoformulations that can sustain therapeutic drug levels for up to two months in rats. The traditional antiretroviral therapy for HIV-1 requires lifelong daily adherence, leading to the development of long-acting ART to overcome this limitation. By transforming tenofovir into long-acting nanoformulations, the researchers have taken a significant step towards a long-acting TFV ProTide.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Jane A. O'Halloran, John Sahrmann, Luis Parra-Rodriguez, Daniel T. Vo, Anne M. Butler, Margaret A. Olsen, William G. Powderly
Summary: The use of integrase strand transfer inhibitors (INSTIs) in treating HIV infection is associated with a 31% increased risk of new-onset diabetes mellitus/hyperglycemia in the 6 months following antiretroviral therapy initiation.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Multidisciplinary Sciences
Suyash Deodhar, Brady Sillman, Aditya N. Bade, Sean N. Avedissian, Anthony T. Podany, JoEllyn M. McMillan, Nagsen Gautam, Brandon Hanson, Bhagya L. Dyavar Shetty, Adam Szlachetka, Morgan Johnston, Michellie Thurman, Daniel J. Munt, Alekha K. Dash, Milica Markovic, Arik Dahan, Yazen Alnouti, Alborz Yazdi, Bhavesh D. Kevadiya, Siddappa N. Byrareddy, Samuel M. Cohen, Benson Edagwa, Howard E. Gendelman
Summary: Ultra-long-acting integrase strand transfer inhibitors were developed through screening a library of nanoformulations. One particular nanocrystal showed potential for yearly dosing, releasing drugs slowly at the injection site and adjacent tissues. Significant plasma drug levels were maintained up to a year after injection.
NATURE COMMUNICATIONS
(2022)