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| ID | Type | Description | Link |
|---|---|---|---|
| UM1AI164560 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| amfAR, The Foundation for AIDS Research | OTHER |
| International AIDS Vaccine Initiative | NETWORK |
| Ichor Medical Systems Incorporated | INDUSTRY |
| National Institute of Allergy and Infectious Diseases (NIAID) |
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Combination approaches will almost certainly be required to generate durable control of HIV in the absence of antiretroviral therapy (a "remission"). In this study, 20 individuals will receive a combination regimen administered during ART and then undergo an analytic treatment interruption (ATI).
The investigators will perform a single arm study of twenty individuals with HIV infection on effective ART. All participants will receive a combination regimen administered during ART and then undergo an analytic treatment interruption. Our strategy has five stages
Follow-up off ART will occur through at least Week 46 (expected) and on or off ART (depending on outcome) through Week 86.
Should this approach work, viral load would be expected to rebound in all individuals a few weeks after the bNAb levels decrease to sub-therapeutic levels. This acute rebound would be followed by a new lower viral load set-point and perhaps a long-term remission.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combination intervention arm | Experimental | All volunteers will receive the combination intervention outlined above. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Combination Intervention | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Grade 3 or Greater Adverse Event Count | Number of participants who experience a new grade 3 or greater adverse event | Week 0 through 102 |
| Proportion of Participants Achieving Post-treatment Control | This will be defined as:
| Week 34 through 86 |
| Measure | Description | Time Frame |
|---|---|---|
| Any Grade 2, 3 or 4 Adverse Event Through Week 62 | Occurrence of any unsolicited adverse events for 28 days after administration of each study agent | Week 0 through 62 |
| Any Serious Adverse Events, Medically Attended Adverse Event, and Potentially Immune-mediated Medical Condition |
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Key Inclusion Criteria
Key Exclusion Criteria
9. Active hepatitis C (HCV) infection. 10. Presence of significant abnormalities on electrocardiogram. 11. History of potential immune-mediated medical conditions. Individuals with isolated Raynaud's phenomenon or localized disease requiring topical therapy alone will not be excluded.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zuckerberg San Francisco General Hospital, University of California San Francisco | San Francisco | California | 94110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41326736 | Derived | Peluso MJ, Sandel DA, Deitchman AN, Kim SJ, Dalhuisen T, Tummala HP, Tiburcio R, Zemelko L, Borgo GM, Singh SS, Schwartz K, Deswal M, Williams MC, Hoh R, Shimoda M, Narpala S, Serebryannyy L, Khalili M, Vendrame E, SenGupta D, Whitmore LS, Tisoncik-Go J, Gale M Jr, Koup RA, Mullins JI, Felber BK, Pavlakis GN, Reeves JD, Petropoulos CJ, Glidden DV, Spitzer MH, Gama L, Caskey M, Nussenzweig MC, Chew KW, Henrich TJ, Yukl SA, Cohn LB, Deeks SG, Rutishauser RL. Correlates of HIV-1 control after combination immunotherapy. Nature. 2026 Feb;650(8100):187-195. doi: 10.1038/s41586-025-09929-5. Epub 2025 Dec 1. |
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The study enrolled 11 individuals. The study was terminated early for one participant as one of the investigational products was set to expire before planned dosing. Ten individuals received the complete set of interventions.
The final study included ten individuals who had initiated ART during the acute, early, or chronic phase of HIV infection (defined as <30 days, between 1-6 months, or ≥6 months following estimated date of acquisition; n = 3, 4, and 3 participants, respectively). Participants were recruited from local clinics.
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| ID | Title | Description |
|---|---|---|
| FG000 | Combination Intervention Arm | All volunteers will receive the combination intervention outlined above. Combination Intervention: (1) IL-12 adjuvanted p24CE DNA prime (p24CE/IL-12) at Weeks 0 and 4 (2) IL-12 adjuvanted DNA boost (p24CE plus p55gag) at Week 12 (3) MVA/HIV62B (MVA62B) boost at Week 20 (4) single dose of two bNAbs (VRC07-523LS and 10-1074, which target CD4 binding site and V3 loop, respectively) at week 24 with a TLR9 agonist (lefitolimod) administered weekly between Weeks 24 and 33 (10 doses) (5) ATI with single dose of VRC07 and 10-1074 at Week 34 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Combination Intervention Arm | All volunteers will receive the combination intervention outlined above. Combination Intervention: (1) IL-12 adjuvanted p24CE DNA prime (p24CE/IL-12) at Weeks 0 and 4 (2) IL-12 adjuvanted DNA boost (p24CE plus p55gag) at Week 12 (3) MVA/HIV62B (MVA62B) boost at Week 20 (4) single dose of two bNAbs (VRC07-523LS and 10-1074, which target CD4 binding site and V3 loop, respectively) at week 24 with a TLR9 agonist (lefitolimod) administered weekly between Weeks 24 and 33 (10 doses) (5) ATI with single dose of VRC07 and 10-1074 at Week 34 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Grade 3 or Greater Adverse Event Count | Number of participants who experience a new grade 3 or greater adverse event | All 11 participants who were enrolled | Posted | Count of Participants | Participants | Week 0 through 102 |
|
All adverse events through through Week 102
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Combination Intervention Arm | All volunteers will receive the combination intervention outlined above. Combination Intervention: (1) IL-12 adjuvanted p24CE DNA prime (p24CE/IL-12) at Weeks 0 and 4 (2) IL-12 adjuvanted DNA boost (p24CE plus p55gag) at Week 12 (3) MVA/HIV62B (MVA62B) boost at Week 20 (4) single dose of two bNAbs (VRC07-523LS and 10-1074, which target CD4 binding site and V3 loop, respectively) at week 24 with a TLR9 agonist (lefitolimod) administered weekly between Weeks 24 and 33 (10 doses) (5) ATI with single dose of VRC07 and 10-1074 at Week 34 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated ALT | Hepatobiliary disorders | Systematic Assessment | Transient. Resolved completely. Possibly related to lefitolimod. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection Site Reaction | Skin and subcutaneous tissue disorders | Systematic Assessment |
Study enrollment was delayed due to the COVID-19 pandemic. Only 11 of the planned 20 were enrolled. One participant was unenrolled due to pending expiration of one of the products. A grade 4 liver event resulted in a temporary FDA hold, which resulted in participants receiving a variable number of lefitolimod doses, and extended the study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Steven Deeks | University of California, San Francisco | 6282068000 | steven.deeks@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 21, 2021 | Sep 22, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
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| NIH |
| Rockefeller University | OTHER |
| Mologen AG | INDUSTRY |
| GeoVax, Inc. | INDUSTRY |
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|
Occurrence of any serious adverse events, medically attended adverse event, and potentially immune-mediated medical condition from the time of administration of the first study injection through 12 months after administration of the final study injection |
| Week 0 through 86 |
| Magnitude of T Cell Responses | We measured the magnitude of the CD8+ T cells to gag conserved elements (CE) 2 weeks after MVA boost (Week 22). We measured new or boosted pre-existing interferon (IFN)É£+ Gag/CE-specific CD8+ T cell responses. The magnitude was determined based on intracellular cytokine staining (ICS) by measuring the frequency of interferon (IFN)É£+ Gag/CE-specific CD8+ T cell responses after 6 hour stimulation with peptide pools matching the CE immunogen. | Week 22 |
| Breadth of T Cell Responses | We measured the breadth of the vaccine-induced T cell response after DNA/MVA vaccination (two weeks after the MVA boost; Week 22). We defined breadth based on the number of conserved epitope (CE) pools with a positive CD8+ T cell responses, as defined by measuring the frequency of interferon (IFN)É£+ Gag/CE-specific CD8+ T cell responses after 6 hour stimulation with peptide pools matching the CE immunogen (using intracellular cytokine staining, ICS). Seven smaller CE pools were tested on each sample. Positive responses were determined based on a magnitude of IFNg+ cells greater than 0.001% of CD8+ T cells after peptide stimulation and after subtraction of background responses. | Week 22 |
| Intact Provirus DNA Levels | The HIV-1 DNA reservoir was estimated using digital droplet PCR (Intact Proviral DNA Assay; IPDA). The frequency of intact proviruses (per million CD4+ T cells) was estimated at baseline and prior to the antiretroviral treatment interruption (Week 34). The change from baseline to Week 34 was calculated. A decrease (negative number) is a better outcome. The units are intact genomes/million CD4+ T cells. | Baseline to pre-interruption (week 34) |
| Participants |
|
| Sex/Gender, Customized | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Proportion of Participants Achieving Post-treatment Control | This will be defined as:
| Eleven participants were enrolled. One received two vaccines and was disenrolled as future investigational products were going to expire. Ten completed the study. | Posted | Count of Participants | Participants | Week 34 through 86 |
|
|
|
| Secondary | Any Grade 2, 3 or 4 Adverse Event Through Week 62 | Occurrence of any unsolicited adverse events for 28 days after administration of each study agent | All enrolled participants | Posted | Number | Number of grade 2-4 AEs | Week 0 through 62 |
|
|
|
| Secondary | Any Serious Adverse Events, Medically Attended Adverse Event, and Potentially Immune-mediated Medical Condition | Occurrence of any serious adverse events, medically attended adverse event, and potentially immune-mediated medical condition from the time of administration of the first study injection through 12 months after administration of the final study injection | All enrolled participants | Posted | Number | Number of serious adverse events | Week 0 through 86 |
|
|
|
| Secondary | Magnitude of T Cell Responses | We measured the magnitude of the CD8+ T cells to gag conserved elements (CE) 2 weeks after MVA boost (Week 22). We measured new or boosted pre-existing interferon (IFN)É£+ Gag/CE-specific CD8+ T cell responses. The magnitude was determined based on intracellular cytokine staining (ICS) by measuring the frequency of interferon (IFN)É£+ Gag/CE-specific CD8+ T cell responses after 6 hour stimulation with peptide pools matching the CE immunogen. | All participants who received therapuetic vaccinations | Posted | Median | Inter-Quartile Range | Percentage of gag INFg+ CD8+ Cells | Week 22 |
|
|
|
| Secondary | Breadth of T Cell Responses | We measured the breadth of the vaccine-induced T cell response after DNA/MVA vaccination (two weeks after the MVA boost; Week 22). We defined breadth based on the number of conserved epitope (CE) pools with a positive CD8+ T cell responses, as defined by measuring the frequency of interferon (IFN)É£+ Gag/CE-specific CD8+ T cell responses after 6 hour stimulation with peptide pools matching the CE immunogen (using intracellular cytokine staining, ICS). Seven smaller CE pools were tested on each sample. Positive responses were determined based on a magnitude of IFNg+ cells greater than 0.001% of CD8+ T cells after peptide stimulation and after subtraction of background responses. | Posted | Median | Inter-Quartile Range | Epitope pools | Week 22 |
|
|
|
| Secondary | Intact Provirus DNA Levels | The HIV-1 DNA reservoir was estimated using digital droplet PCR (Intact Proviral DNA Assay; IPDA). The frequency of intact proviruses (per million CD4+ T cells) was estimated at baseline and prior to the antiretroviral treatment interruption (Week 34). The change from baseline to Week 34 was calculated. A decrease (negative number) is a better outcome. The units are intact genomes/million CD4+ T cells. | Study participants who enrolled and who were followed through to the analytic treatment interruption (Week 34) | Posted | Mean | Standard Deviation | Intact genomes/million CD4+ T cells | Baseline to pre-interruption (week 34) |
|
|
|
| Post-Hoc | Virologic Rebound | Number of participants who exhibit two consecutive measurements HIV RNA >200 copies/mL during the analytic treatment interruption | Posted | Count of Participants | Participants | Week 34 to 86 |
|
|
|
| Post-Hoc | Number of Participants Resuming Antiretroviral Therapy | Number of participants who resumed antiretroviral therapy after treatment interruption due to protocol-defined events, including virologic failure as defined in the protocol, CD4+ T cell declines as defined in the protocol, or clinical progression | All enrolled participants | Posted | Count of Participants | Participants | Week 34 to 86 |
|
|
|
| Post-Hoc | Acute Retroviral Rebound | Proportion experiencing any clinically defined episode of acute retroviral syndrome | Posted | Count of Participants | Participants | Week 34 to 86 |
|
|
|
| Post-Hoc | Number of Participants With Confirmed Declines in CD4+ T Cell Counts (> 50%) | Number of participants experiencing confirmed declines (two consecutive measurements) in CD4+ T cell counts (> 50% from baseline) | All enrolled participants | Posted | Count of Participants | Participants | Week 34 to 86 |
|
|
|
| 0 |
| 11 |
| 3 |
| 11 |
| 11 |
| 11 |
|
| Hypomania | Psychiatric disorders | Systematic Assessment | Severe hypomania event in a person with bipolar disorder. Not study related. Resolved. |
|
| Suicide attempt | Psychiatric disorders | Systematic Assessment | Not study related. |
|
| Malaise | General disorders | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | Non-systematic Assessment |
|
| Vision Changes | Eye disorders | Non-systematic Assessment |
|
| Inguinal swelling | Immune system disorders | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Chills | General disorders | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Elevated ALT | Hepatobiliary disorders | Systematic Assessment |
|
| Fatigue | General disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Hernia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
|
| Gastroesophageal reflux | Gastrointestinal disorders | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Acute SARS-CoV-2 Infection | Infections and infestations | Non-systematic Assessment |
|
| Anal warts | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Mental health disorders | Psychiatric disorders | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Basal cell carcinoma | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Bladder infection | Infections and infestations | Non-systematic Assessment |
|
| Body swelling | General disorders | Non-systematic Assessment |
|
| Bunion | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Cellulitis | Infections and infestations | Non-systematic Assessment |
|
| Cervical lymph node swelling | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| Chlamydia infection | Infections and infestations | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Low calcium | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | Non-systematic Assessment |
|
| Fever | General disorders | Non-systematic Assessment |
|
| Dysuria | Renal and urinary disorders | Non-systematic Assessment |
|
| Elevated blood pressure | Cardiac disorders | Systematic Assessment |
|
| High glucose | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| High potassium | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| High bilirubin | Hepatobiliary disorders | Non-systematic Assessment |
|
| Gonorrhea | Infections and infestations | Non-systematic Assessment |
|
| Hearing loss | Ear and labyrinth disorders | Non-systematic Assessment |
|
| Herpes infection | Infections and infestations | Non-systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | Non-systematic Assessment |
|
| Influenza A | Infections and infestations | Non-systematic Assessment |
|
| Kidney stone | Renal and urinary disorders | Non-systematic Assessment |
|
| Leg cramps | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Loss of smell | Nervous system disorders | Non-systematic Assessment |
|
| Low glucose | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Low phosphate | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Sweats | General disorders | Non-systematic Assessment |
|
| Non-specific viral infection | Infections and infestations | Non-systematic Assessment |
|
| Perianal tenderness | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Shingles | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Shoulder pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Pharyngitis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Stye | Eye disorders | Non-systematic Assessment |
|
| Syphillis | Infections and infestations | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | Non-systematic Assessment |
|
| Vomitting | Gastrointestinal disorders | Non-systematic Assessment |
|
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| D015229 |
| Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |