Clinical trials aimed at HIV cure or remission: new pathways and lessons learned

A CRISPR-Cas Cure for HIV/AIDS

(2023) Mouraya Hussein et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Phenotypic signatures of immune selection in HIV-1 reservoir cells

(2023) Weiwei Sun et al.   NATURE

HIV silencing and cell survival signatures in infected T cell reservoirs

(2023) Iain C. Clark et al.   NATURE

HIV-1 remission and possible cure in a woman after haplo-cord blood transplant

(2023) Jingmei Hsu et al.   CELL

In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation

(2023) Björn-Erik Ole Jensen et al.   NATURE MEDICINE

Prevention, treatment and cure of HIV infection

(2023) Raphael J. Landovitz et al.   NATURE REVIEWS MICROBIOLOGY

Soluble immune checkpoints as correlates for HIV persistence and T cell function in people with HIV on antiretroviral therapy

(2023) Chris Y. Chiu et al.   Frontiers in Immunology

Monocyte-derived macrophages contain persistent latent HIV reservoirs

(2023) Rebecca T. Veenhuis et al.   Nature Microbiology

Preclinical safety and biodistribution of CRISPR targeting SIV in non-human primates

(2023) Tricia H. Burdo et al.   GENE THERAPY

Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial

(2023) Jesper D. Gunst et al.   NATURE MEDICINE

Safety and virologic impact of the IL-15 superagonist N-803 in people living with HIV: a phase 1 trial

(2022) Jeffrey S. Miller et al.   NATURE MEDICINE

Pembrolizumab induces HIV latency reversal in people living with HIV and cancer on antiretroviral therapy

(2022) Thomas S. Uldrick et al.   Science Translational Medicine

Immune checkpoint blockade in HIV

(2022) Celine Gubser et al.   EBioMedicine

Effect of 3BNC117 and romidepsin on the HIV-1 reservoir in people taking suppressive antiretroviral therapy (ROADMAP): a randomised, open-label, phase 2A trial

(2022) Henning Gruell et al.   Lancet Microbe

Combination anti-HIV antibodies provide sustained virological suppression

(2022) Michael C. Sneller et al.   NATURE

Prolonged viral suppression with anti-HIV-1 antibody therapy

(2022) Christian Gaebler et al.   NATURE

Safety and tolerability of AAV8 delivery of a broadly neutralizing antibody in adults living with HIV: a phase 1, dose-escalation trial

(2022) Joseph P. Casazza et al.   NATURE MEDICINE

Safety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial

(2022) Boris Julg et al.   NATURE MEDICINE

Intact HIV Proviruses Persist in the Brain Despite Viral Suppression with ART

(2022) Catherine R. Cochrane et al.   ANNALS OF NEUROLOGY

Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques

(2022) Victoria E. K. Walker-Sperling et al.   Nature Communications

Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b/2a, randomized trial

(2022) Jesper D. Gunst et al.   NATURE MEDICINE

Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial

(2022) Lucia Bailón et al.   NATURE MEDICINE

The BCL-2 Inhibitor Venetoclax Augments Immune Effector Function Mediated by Fas Ligand, TRAIL, and Perforin/Granzyme B, Resulting in Reduced Plasma Viremia and Decreased HIV Reservoir Size during Acute HIV Infection in a Humanized Mouse Model

(2022) Aswath P. Chandrasekar et al.   JOURNAL OF VIROLOGY

Impact of anti-PD-1 and anti-CTLA-4 on the HIV reservoir in people living with HIV with cancer on antiretroviral therapy: The AIDS Malignancy Consortium-095 study

(2021) Thomas A Rasmussen et al.   CLINICAL INFECTIOUS DISEASES

TLR7 agonist, N6-LS and PGT121 delayed viral rebound in SHIV-infected macaques after antiretroviral therapy interruption

(2021) Denise C. Hsu et al.   PLoS Pathogens

Suspected Immune-Related Adverse Events with an Anti-PD-1 Inhibitor in Healthy People with HIV

(2021) Cynthia L. GAY et al.   JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES

Broadly neutralizing antibodies for HIV-1 prevention and therapy

(2021) Boris Julg et al.   SEMINARS IN IMMUNOLOGY

The TLR7 agonist vesatolimod induced a modest delay in viral rebound in HIV controllers after cessation of antiretroviral therapy

(2021) Devi SenGupta et al.   Science Translational Medicine

Therapeutic Potential of IL-15 and N-803 in HIV/SIV Infection

(2021) Olivia Harwood et al.   Viruses-Basel

Viral, inflammatory, and reservoir characteristics of posttreatment controllers

(2021) James McMahon et al.   Current Opinion in HIV and AIDS

The Interplay Among HIV, LINE-1, and the Interferon Signaling System

(2021) Xu Zhao et al.   Frontiers in Immunology

Advancing HIV Broadly Neutralizing Antibodies: From Discovery to the Clinic

(2021) David A. Spencer et al.   Frontiers in Public Health

In Vivo Dynamics of the Latent Reservoir for HIV-1: New Insights and Implications for Cure

(2021) Janet D. Siliciano et al.   Annual Review of Pathology-Mechanisms of Disease

Stable Latent HIV Infection and Low-level Viremia Despite Treatment With the Broadly Neutralizing Antibody VRC07-523LS and the Latency Reversal Agent Vorinostat

(2021) Cynthia L Gay et al.   JOURNAL OF INFECTIOUS DISEASES

Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial

(2021) Kathryn E. Stephenson et al.   NATURE MEDICINE

Interleukin-7 Biology and Its Effects on Immune Cells: Mediator of Generation, Differentiation, Survival, and Homeostasis

(2021) Deng Chen et al.   Frontiers in Immunology

Antiretroviral therapy alone versus antiretroviral therapy with a kick and kill approach, on measures of the HIV reservoir in participants with recent HIV infection (the RIVER trial): a phase 2, randomised trial

(2020) Sarah Fidler et al.   LANCET

Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity

(2020) Julia Niessl et al.   NATURE MEDICINE

Different human resting memory CD4+ T cell subsets show similar low inducibility of latent HIV-1 proviruses

(2020) Kyungyoon J. Kwon et al.   Science Translational Medicine

BCL-2 antagonism sensitizes cytotoxic T cell–resistant HIV reservoirs to elimination ex vivo

(2020) Yanqin Ren et al.   JOURNAL OF CLINICAL INVESTIGATION

CTLA-4 and PD-1 dual blockade induces SIV reactivation without control of rebound after antiretroviral therapy interruption

(2020) Justin Harper et al.   NATURE MEDICINE

HIVconsv Vaccines and Romidepsin in Early-Treated HIV-1-Infected Individuals: Safety, Immunogenicity and Effect on the Viral Reservoir (Study BCN02)

(2020) Beatriz Mothe et al.   Frontiers in Immunology

Combination of CD8β depletion and IL-15 superagonist N-803 induces virus reactivation in SHIV-infected, long-term ART-treated rhesus macaques

(2020) Julia B. McBrien et al.   JOURNAL OF VIROLOGY

HSF1 inhibition attenuates HIV-1 latency reversal mediated by several candidate LRAs In Vitro and Ex Vivo

(2020) Andrew Timmons et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The Use of Toll-Like Receptor Agonists in HIV-1 Cure Strategies

(2020) Janne Tegder Martinsen et al.   Frontiers in Immunology

Vesatolimod, a toll-like receptor 7 agonist, induces immune activation in virally suppressed adults with HIV-1

(2020) Sharon A Riddler et al.   CLINICAL INFECTIOUS DISEASES

Safety, immune and anti-viral effects of pegylated interferon alpha 2b administration in ART-suppressed individuals: Results of pilot clinical trial

(2020) Emmanouil Papasavvas et al.   AIDS RESEARCH AND HUMAN RETROVIRUSES

Clinical Impact of Pretreatment Human Immunodeficiency Virus Drug Resistance in People Initiating Nonnucleoside Reverse Transcriptase Inhibitor–Containing Antiretroviral Therapy: A Systematic Review and Meta-analysis

(2020) Silvia Bertagnolio et al.   JOURNAL OF INFECTIOUS DISEASES

Antigen-driven clonal selection shapes the persistence of HIV-1–infected CD4+ T cells in vivo

(2020) Francesco R. Simonetti et al.   JOURNAL OF CLINICAL INVESTIGATION

Low Inducibility of Latent Human Immunodeficiency Virus Type 1 Proviruses as a Major Barrier to Cure

(2020) Janet D Siliciano et al.   JOURNAL OF INFECTIOUS DISEASES

Reiterative Enrichment and Authentication of CRISPRi Targets (REACT) identifies the proteasome as a key contributor to HIV-1 latency

(2019) Zichong Li et al.   PLoS Pathogens

HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation

(2019) Ravindra K. Gupta et al.   NATURE

Effects of 24 Week Toll-Like Receptor 9 Agonist Treatment in HIV-1+ Individuals

(2019) Line K. Vibholm et al.   AIDS

Safety and efficacy of VRC01 broadly neutralising antibodies in adults with acutely treated HIV (RV397): a phase 2, randomised, double-blind, placebo-controlled trial

(2019) Trevor A Crowell et al.   Lancet HIV

NK Response Correlates with HIV Decrease in Pegylated IFN-α2a–Treated Antiretroviral Therapy–Suppressed Subjects

(2019) Emmanouil Papasavvas et al.   JOURNAL OF IMMUNOLOGY

TLR9 agonist MGN1703 enhances B cell differentiation and function in lymph nodes

(2019) Mariane H. Schleimann et al.   EBioMedicine

The Role of the BCL-2 Family of Proteins in HIV-1 Pathogenesis and Persistence

(2019) Aswath P. Chandrasekar et al.   CLINICAL MICROBIOLOGY REVIEWS

The replication-competent HIV-1 latent reservoir is primarily established near the time of therapy initiation

(2019) Melissa-Rose Abrahams et al.   Science Translational Medicine

T‐cell exhaustion in HIV infection

(2019) Craig Fenwick et al.   IMMUNOLOGICAL REVIEWS

Programmed cell death-1 contributes to the establishment and maintenance of HIV-1 latency

(2018) Vanessa A. Evans et al.   AIDS

HIV-1 Infection and Type 1 Interferon: Navigating through Uncertain Waters

(2018) Sho Sugawara et al.   AIDS RESEARCH AND HUMAN RETROVIRUSES

Inconsistent HIV reservoir dynamics and immune responses following anti-PD-1 therapy in cancer patients with HIV infection

(2018) E P Scully et al.   ANNALS OF ONCOLOGY

An open-label, multiple ascending dose study of the anti-CTLA-4 antibody ipilimumab in viremic HIV patients

(2018) Elizabeth Colston et al.   PLoS One

TLR7 agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral therapy

(2018) So-Yon Lim et al.   Science Translational Medicine

CRISPR/Cas9 system targeting regulatory genes of HIV-1 inhibits viral replication in infected T-cell cultures

(2018) Youdiil Ophinni et al.   Scientific Reports

Combination therapy with anti-HIV-1 antibodies maintains viral suppression

(2018) Pilar Mendoza et al.   NATURE

Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals

(2018) Yotam Bar-On et al.   NATURE MEDICINE

Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys

(2018) Erica N. Borducchi et al.   NATURE

A majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation

(2018) Daniel B. Reeves et al.   Nature Communications

Anti-retroviral antibody FcγR-mediated effector functions

(2017) Stylianos Bournazos et al.   IMMUNOLOGICAL REVIEWS

Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency

(2017) Nancie M. Archin et al.   JOURNAL OF CLINICAL INVESTIGATION

Clinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 Infected Participants on Suppressive Antiretroviral Therapy

(2017) Cynthia L. Gay et al.   JOURNAL OF INFECTIOUS DISEASES

ALT-803 Transiently Reduces Simian Immunodeficiency Virus Replication in the Absence of Antiretroviral Treatment

(2017) Amy L. Ellis-Connell et al.   JOURNAL OF VIROLOGY

Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy

(2017) Angela Tsai et al.   JOURNAL OF VIROLOGY

The TLR9 agonist MGN1703 triggers a potent type I interferon response in the sigmoid colon

(2017) A R Krarup et al.   Mucosal Immunology

Early antibody therapy can induce long-lasting immunity to SHIV

(2017) Yoshiaki Nishimura et al.   NATURE

Antibody 10-1074 suppresses viremia in HIV-1-infected individuals

(2017) Marina Caskey et al.   NATURE MEDICINE

Heat Shock Protein 90 Facilitates Latent HIV Reactivation through Maintaining the Function of Positive Transcriptional Elongation Factor b (p-TEFb) under Proteasome Inhibition

(2016) Xiao-Yan Pan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Prime, Shock, and Kill: Priming CD4 T Cells from HIV Patients with a BCL-2 Antagonist before HIV Reactivation Reduces HIV Reservoir Size

(2016) Nathan W. Cummins et al.   JOURNAL OF VIROLOGY

A Novel Toll-Like Receptor 9 Agonist, MGN1703, Enhances HIV-1 Transcription and NK Cell-Mediated Inhibition of HIV-1-Infected Autologous CD4+T Cells

(2016) Rasmus Offersen et al.   JOURNAL OF VIROLOGY

PD-1+ and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals

(2016) Riddhima Banga et al.   NATURE MEDICINE

Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption

(2016) Katharine J. Bar et al.   NEW ENGLAND JOURNAL OF MEDICINE

HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1

(2016) T. Schoofs et al.   SCIENCE

Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo

(2016) C.-L. Lu et al.   SCIENCE

Initiation of antiretroviral therapy before detection of colonic infiltration by HIV reduces viral reservoirs, inflammation and immune activation

(2016) Trevor A Crowell et al.   Journal of the International AIDS Society

A Cas9 Ribonucleoprotein Platform for Functional Genetic Studies of HIV-Host Interactions in Primary Human T Cells

(2016) Judd F. Hultquist et al.   Cell Reports

TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection

(2016) Glen M. Chew et al.   PLoS Pathogens

CD4+ T Cells Expressing PD-1, TIGIT and LAG-3 Contribute to HIV Persistence during ART

(2016) Rémi Fromentin et al.   PLoS Pathogens

A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4+ T-Cells to Recognition by Cytotoxic T-Lymphocytes

(2016) R. Brad Jones et al.   PLoS Pathogens

Establishment and stability of the latent HIV-1 DNA reservoir

(2016) Johanna Brodin et al.   eLife

Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial

(2016) Steffen Leth et al.   Lancet HIV

HIV DNA Set Point is Rapidly Established in Acute HIV Infection and Dramatically Reduced by Early ART

(2016) Jintanat Ananworanich et al.   EBioMedicine

Effect of ipilimumab on the HIV reservoir in an HIV-infected individual with metastatic melanoma

(2015) Fiona Wightman et al.   AIDS

Understanding HIV Latency: The Road to an HIV Cure

(2015) Matthew S. Dahabieh et al.   Annual Review of Medicine

Early Initiation Rather Than Prolonged Duration of Antiretroviral Therapy in HIV Infection Contributes to the Normalization of CD8 T-Cell Counts

(2015) Wei Cao et al.   CLINICAL INFECTIOUS DISEASES

Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117

(2015) Marina Caskey et al.   NATURE

Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations

(2015) Kai Deng et al.   NATURE

Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection

(2015) Rebecca M. Lynch et al.   Science Translational Medicine

The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo

(2015) Ole S. Søgaard et al.   PLoS Pathogens

HIV-1 Expression Within Resting CD4+ T Cells After Multiple Doses of Vorinostat

(2014) N. M. Archin et al.   JOURNAL OF INFECTIOUS DISEASES

Modeling the Timing of Antilatency Drug Administration during HIV Treatment

(2014) J. Petravic et al.   JOURNAL OF VIROLOGY

Targeted genome editing in human repopulating haematopoietic stem cells

(2014) Pietro Genovese et al.   NATURE

Measuring Turnover of SIV DNA in Resting CD4+ T Cells Using Pyrosequencing: Implications for the Timing of HIV Eradication Therapies

(2014) Jeanette C. Reece et al.   PLoS One

Specific HIV integration sites are linked to clonal expansion and persistence of infected cells

(2014) F. Maldarelli et al.   SCIENCE

Activation of HIV Transcription with Short-Course Vorinostat in HIV-Infected Patients on Suppressive Antiretroviral Therapy

(2014) Julian H. Elliott et al.   PLoS Pathogens

Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial

(2014) Thomas A Rasmussen et al.   Lancet HIV

Interleukin-7 promotes HIV persistence during antiretroviral therapy

(2013) C. Vandergeeten et al.   BLOOD

What the Infectious Disease Physician Needs to Know About Pegylated Interferon and Ribavirin

(2013) N. Gara et al.   CLINICAL INFECTIOUS DISEASES

Susceptibility to CD8 T-Cell–Mediated Killing Influences the Reservoir of Latently HIV-1–Infected CD4 T Cells

(2013) Maria J. Buzon et al.   JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES

Effects of Alpha Interferon Treatment on Intrinsic Anti-HIV-1 Immunity In Vivo

(2013) M. Abdel-Mohsen et al.   JOURNAL OF VIROLOGY

HIV Latency

(2013) R. F. Siliciano et al.   Cold Spring Harbor Perspectives in Medicine

Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study

(2013) Asier Sáez-Cirión et al.   PLoS Pathogens

Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies

(2012) Peter D. Kwong et al.   IMMUNITY

Pegylated Interferon Alfa-2a Monotherapy Results in Suppression of HIV Type 1 Replication and Decreased Cell-Associated HIV DNA Integration

(2012) Livio Azzoni et al.   JOURNAL OF INFECTIOUS DISEASES

Cell-Based Measures of Viral Persistence Are Associated With Immune Activation and Programmed Cell Death Protein 1 (PD-1)–Expressing CD4+ T cells

(2012) Hiroyu Hatano et al.   JOURNAL OF INFECTIOUS DISEASES

Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy

(2012) N. M. Archin et al.   NATURE

Shock and kill

(2012) Steven G. Deeks   NATURE

Interferon-Alpha Administration Enhances CD8+ T Cell Activation in HIV Infection

(2012) Maura Manion et al.   PLoS One

Role of retroviral restriction factors in the interferon- -mediated suppression of HIV-1 in vivo

(2012) S. K. Pillai et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques

(2011) E. Lugli et al.   BLOOD

Nonproteasomal Targets of the Proteasome Inhibitors Bortezomib and Carfilzomib: a Link to Clinical Adverse Events

(2011) S. Arastu-Kapur et al.   CLINICAL CANCER RESEARCH

Second Generation Proteasome Inhibitors: Carfilzomib and Immunoproteasome-Specific Inhibitors (IPSIs)

(2011) D. J. Kuhn et al.   CURRENT CANCER DRUG TARGETS

Homeostatic Proliferation Fails to Efficiently Reactivate HIV-1 Latently Infected Central Memory CD4+ T Cells

(2011) Alberto Bosque et al.   PLoS Pathogens

HIV-1 viruses detected during episodic blips following interleukin-7 administration are similar to the viruses present before and after interleukin-7 therapy

(2010) Hiromi Imamichi et al.   AIDS

Role of Interleukin-2 in Patients with HIV Infection

(2010) Sarah L. Pett et al.   DRUGS

Interleukin-2 Receptor Signaling: At the Interface between Tolerance and Immunity

(2010) Thomas R. Malek et al.   IMMUNITY

Safety, Tolerability, and Mechanisms of Antiretroviral Activity of Pegylated Interferon Alfa‐2a in HIV‐1–Monoinfected Participants: A Phase II Clinical Trial

(2010) David M. Asmuth et al.   JOURNAL OF INFECTIOUS DISEASES

The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors

(2010) Taro Kawai et al.   NATURE IMMUNOLOGY

IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection

(2009) I. Sereti et al.   BLOOD

Enhanced T cell recovery in HIV-1–infected adults through IL-7 treatment

(2009) Yves Levy et al.   JOURNAL OF CLINICAL INVESTIGATION

HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation

(2009) Nicolas Chomont et al.   NATURE MEDICINE

Long-Term Control of HIV byCCR5Delta32/Delta32 Stem-Cell Transplantation

(2009) Gero Hütter et al.   NEW ENGLAND JOURNAL OF MEDICINE