4.7 Review

Update and latest advances in antiretroviral therapy

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Review Immunology

Clinical Trials of Broadly Neutralizing Monoclonal Antibodies for Human Immunodeficiency Virus Prevention: A Review

Sharana Mahomed et al.

Summary: Passive immunization with bnAbs shows potential in reducing global HIV infections, with newly developed highly potent bnAbs showing promise for HIV prevention. Published data indicate these antibodies are safe and effective, and if proven to be successful, could have a positive impact on HIV vaccine development.

JOURNAL OF INFECTIOUS DISEASES (2021)

Article Microbiology

Impact of HIV-1 Resistance-Associated Mutations on Susceptibility to Doravirine: Analysis of Real-World Clinical Isolates

Ernest Asante-Appiah et al.

Summary: The study aimed to investigate the impact of resistance-associated mutations on the susceptibility of clinical isolates to the NNRTI doravirine, finding that most patients showed high susceptibility to doravirine.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

Article Microbiology

Absence of Lenacapavir (GS-6207) Phenotypic Resistance in HIV Gag Cleavage Site Mutants and in Isolates with Resistance to Existing Drug Classes

Nicolas Margot et al.

Summary: LEN is a potent inhibitor of HIV-1 capsid and has shown strong antiviral response in mutants with Gag cleavage site mutations and resistance to other drug classes. While LEN demonstrated wild-type susceptibility, reduced susceptibility was observed for control drugs.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

Article Infectious Diseases

Long-acting drugs and formulations for the treatment and prevention of HIV infection

Charles Flexner et al.

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 Biochemistry & Molecular Biology

Allosteric HIV Integrase Inhibitors Promote Formation of Inactive Branched Polymers via Homomeric Carboxy-Terminal Domain Interactions

Kushol Gupta et al.

Summary: The study reveals that the IN aggregates induced by ALLINIs exhibit weak three-dimensional gel characteristics with a fractal-like nature. Their formation is influenced by the host factor LEDGF/p75 and ex vivo resistance substitutions.

STRUCTURE (2021)

Article Biochemistry & Molecular Biology

Safety and pharmacokinetics of islatravir subdermal implant for HIV-1 pre-exposure prophylaxis: a randomized, placebo-controlled phase 1 trial

Randolph P. Matthews et al.

Summary: In a 12-week trial, the subdermal implant of the HIV-1 antiretroviral islatravir demonstrated sustained drug release in humans at two different doses, showing efficacy and good safety profile. Further investigation is warranted to explore islatravir implants as a potential strategy for HIV prevention.

NATURE MEDICINE (2021)

Review Virology

Integrase Strand Transfer Inhibitors Are Effective Anti-HIV Drugs

Steven J. Smith et al.

Summary: INSTIs are recommended as first-line treatment for HIV-1 infection, with second-generation drugs effective against resistant viruses and minimal emergence of resistance. They are expected to play a significant role in PrEP.

VIRUSES-BASEL (2021)

Article Microbiology

A Phase I Evaluation of the Pharmacokinetics and Tolerability of the HIV-1 Maturation Inhibitor GSK3640254 and Tenofovir Alafenamide/Emtricitabine in Healthy Participants

Teodora Pene Dumitrescu et al.

Summary: The study found that coadministration of GSK3640254 with TAF/FTC resulted in slightly lower TAF plasma concentrations and maximum observed concentrations compared to when TAF/FTC was administered alone, while the pharmacokinetics of TFV and FTC were similar. GSK3640254 did not significantly affect the steady-state pharmacokinetics of TAF, TFV, or FTC in healthy participants under fed conditions.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

Review Chemistry, Medicinal

An insight on medicinal aspects of novel HIV-1 capsid protein inhibitors

Lin Sun et al.

Summary: The capsid of HIV-1, composed of a protein called capsid protein, plays a significant role in the virus life cycle and is a target for new inhibitors. Novel HIV-1 inhibitors binding to capsid proteins have been developed successfully, with some expected to be approved drugs.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Medicine, General & Internal

Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition

L. Corey et al.

Summary: The study found that broadly neutralizing antibodies did not prevent HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates indicated that prophylaxis with broadly neutralizing antibodies may be effective.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Review Virology

HIV-1 Entry and Membrane Fusion Inhibitors

Tianshu Xiao et al.

Summary: HIV-1 infection begins with virion attachment to host cell membrane through Env, binding to receptors CD4 and coreceptors CCR5/CXCR4; understanding the structural biology of HIV-1 Env aids in designing antiviral therapeutics targeting viral entry.

VIRUSES-BASEL (2021)

Review Virology

HIV Protease: Historical Perspective and Current Research

Irene T. Weber et al.

Summary: The HIV protease is a key target for antiviral therapy, but drug resistance poses a growing threat. Dr. Stephen Oroszlan's contributions to understanding the function of the HIV protease and the development of clinical inhibitors are highlighted. Drug-resistant protease variants serve as valuable models for studying resistance mechanisms and evolution.

VIRUSES-BASEL (2021)

Article Immunology

Islatravir in combination with doravirine for treatment-naive adults with HIV-1 infection receiving initial treatment with islatravir, doravirine, and lamivudine: a phase 2b, randomised, double-blind, dose-ranging trial

Jean-Michel Molina et al.

Summary: The study aimed to evaluate the efficacy and safety of islatravir-based regimens for HIV-1 treatment. Results showed that treatment regimens containing islatravir and doravirine demonstrated antiviral efficacy and were well tolerated at different doses.

LANCET HIV (2021)

Article Microbiology

A Small Molecule, ACAi-028, with Anti-HIV-1 Activity Targets a Novel Hydrophobic Pocket on HIV-1 Capsid

Travis Chia et al.

Summary: ACAi-028, a small molecule identified through in vitro screening, inhibits HIV-1 replication by targeting a hydrophobic pocket in the N-terminal domain of the HIV-1 capsid. It interacts with specific amino acid residues in the CA-NTD pocket, demonstrating anti-HIV-1 activity by affecting core disassembly and stability. These findings suggest ACAi-028 as a promising CA inhibitor for HIV-1 treatment.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

Article Medicine, General & Internal

Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women

Raphael J. Landovitz et al.

Summary: The study showed that injectable Cabotegravir was more effective in preventing HIV infection among MSM and transgender women compared to daily oral Tenofovir Disoproxil Fumarate-Emtricitabine. Strategies are needed to prevent INSTI resistance in cases of Cabotegravir PrEP failure.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Multidisciplinary Sciences

Lipophilic nanocrystal prodrug-release defines the extended pharmacokinetic profiles of a year-long cabotegravir

Nagsen Gautam et al.

Summary: The study demonstrates that a once yearly injection of long-acting cabotegravir is more effective in preventing HIV-1 transmission compared to daily oral drugs. The slow release of the drug in mice and rats results in sustained plasma levels above the 90% inhibitory concentration for a year after a single dose.

NATURE COMMUNICATIONS (2021)

Article Biochemistry & Molecular Biology

Optimized binding of substituted quinoline ALLINIs within the HIV-1 integrase oligomer

Jian Sun et al.

Summary: This study explores the dual properties of ALLINIs in blocking viral integration and impacting viral maturation, and demonstrates that enhancing interactions between the inhibitor and all three IN subunits can improve antiviral potency and shift selectivity towards the viral maturation stage.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

Review Chemistry, Multidisciplinary

Medicinal chemistry strategies for discovering antivirals effective against drug-resistant viruses

Yue Ma et al.

Summary: This article discusses strategies for discovering antiviral compounds specifically designed to combat drug resistance, including targeting proteins, drug conformation, new binding sites, and host factors as potential therapeutic approaches.

CHEMICAL SOCIETY REVIEWS (2021)

Article Microbiology

Translational Approach to Predicting the Efficacy of Maraviroc-Based Regimens as HIV Preexposure Prophylaxis

Nithya Srinivas et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2020)

Article Medicine, General & Internal

Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression

Susan Swindells et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Review Biochemistry & Molecular Biology

Curing HIV: Seeking to Target and Clear Persistent Infection

David M. Margolis et al.

Review Biochemistry & Molecular Biology

Evolving understanding of HIV-1 reverse transcriptase structure, function, inhibition, and resistance

Francesc Xavier Ruiz et al.

CURRENT OPINION IN STRUCTURAL BIOLOGY (2020)

Review Pharmacology & Pharmacy

Novel Approaches Towards a Functional Cure of HIV/AIDS

Lucia Bailon Alvarez et al.

Article Medicine, General & Internal

Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection

Michael Kozal et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Article Multidisciplinary Sciences

Clinical targeting of HIV capsid protein with a long-acting small molecule

John O. Link et al.

NATURE (2020)

Review Pharmacology & Pharmacy

HIV-1 Integrase Inhibitors: A Comparative Review of Efficacy and Safety

Kimberly K. Scarsi et al.

Article Immunology

Long-Acting Injectable Cabotegravir plus Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials

Giuliano Rizzardini et al.

JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES (2020)

Review Medicine, General & Internal

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults 2020 Recommendations of the International Antiviral Society-USA Panel

Michael S. Saag et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2020)

Article Biochemistry & Molecular Biology

A novel HIV-1 inhibitor that blocks viral replication and rescues APOBEC3s by interrupting vif/CBFβ interaction

Sizhu Duan et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2020)

Review Pharmacology & Pharmacy

Structural Biology of HIV Integrase Strand Transfer Inhibitors

Ilona K. Jozwik et al.

TRENDS IN PHARMACOLOGICAL SCIENCES (2020)

Review Virology

HIV-1 Maturation: Lessons Learned from Inhibitors

Alex B. Kleinpeter et al.

VIRUSES-BASEL (2020)

Review Pharmacology & Pharmacy

Recent discoveries in HIV-1 reverse transcriptase inhibitors

Shuang-Xi Gu et al.

CURRENT OPINION IN PHARMACOLOGY (2020)

Article Multidisciplinary Sciences

Structural and mechanistic bases for a potent HIV-1 capsid inhibitor

Stephanie M. Bester et al.

SCIENCE (2020)

Review Immunology

Review: HIV-1 phylogeny during suppressive antiretroviral therapy

Michael J. Bale et al.

CURRENT OPINION IN HIV AND AIDS (2019)

Article Medicine, General & Internal

Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV

Willem D. F. Venter et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

Review Pharmacology & Pharmacy

Ribonuclease H, an unexploited target for antiviral intervention against HIV and hepatitis B virus

Enzo Tramontano et al.

ANTIVIRAL RESEARCH (2019)

Review Biochemistry & Molecular Biology

Current and emerging non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV-1 treatment

Yali Wang et al.

EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY (2019)

Article Infectious Diseases

Update on Adverse Effects of HIV Integrase Inhibitors

Agnieszka Kolakowska et al.

CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES (2019)

Article Chemistry, Medicinal

Inhibitors of HIV-1 Attachment: The Discovery and Development of Temsavir and its Prodrug Fostemsavir

Nicholas A. Meanwell et al.

JOURNAL OF MEDICINAL CHEMISTRY (2018)

Review Medicine, Research & Experimental

Novel Latency Reversal Agents for HIV-1 Cure

Adam M. Spivak et al.

ANNUAL REVIEW OF MEDICINE, VOL 69 (2018)

Article Microbiology

Extended-Duration MK-8591-Eluting Implant as a Candidate for HIV Treatment and Prevention

Stephanie E. Barrett et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2018)

Review Virology

Viral reverse transcriptases

Luis Menendez-Arias et al.

VIRUS RESEARCH (2017)

Article Medicine, General & Internal

Safety and Efficacy of a Dapivirine Vaginal Ring for HIV Prevention in Women

A. Nel et al.

NEW ENGLAND JOURNAL OF MEDICINE (2016)

Article Multidisciplinary Sciences

Structural basis of HIV inhibition by translocation-defective RT inhibitor 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA)

Zhe Li Salie et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

Review Infectious Diseases

Efavirenz and the CNS: what we already know and questions that need to be answered

Nadezda Apostolova et al.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2015)

Article Biochemistry & Molecular Biology

4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) Inhibits HIV-1 Reverse Transcriptase with Multiple Mechanisms

Eleftherios Michailidis et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2014)

Article Infectious Diseases

Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV

Erik De Clercq

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS (2009)