Combinatorial Therapy to Induce an HIV Remission

NCT04357821 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: 18-26957UM1AI164560
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

HIV/AIDS

Outcome Measures

Primary Outcomes (2)

• 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: 1. Participants who fail to show any consistent rebound above 400 copies RNA/mL between Week 12 of the ATI (when bNAb levels wane) and Week 36 of the ATI 2. Participants who exhibit a rebound and eventually achieve 24 weeks of virus control will be considered as having achieved post-treatment control

  Week 34 through 86

Secondary Outcomes (5)

• Any Grade 2, 3 or 4 Adverse Event Through Week 62

  Week 0 through 62

• Any Serious Adverse Events, Medically Attended Adverse Event, and Potentially Immune-mediated Medical Condition

  Week 0 through 86

• Magnitude of T Cell Responses

  Week 22

• Breadth of T Cell Responses

  Week 22

• Intact Provirus DNA Levels

  Baseline to pre-interruption (week 34)

Study Arms (1)

Combination intervention arm

EXPERIMENTAL

All volunteers will receive the combination intervention outlined above.

Drug: Combination Intervention

Interventions

Combination Intervention DRUG

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

Combination intervention arm

Eligibility Criteria

• Age: 18 Years - 67 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent.
• Age ≤67 years at the time of enrollment for those who started treatment during early infection and \<65 years for those who started treatment during chronic infection.
• Documented HIV-1 infection.
• On continuous antiretroviral therapy for at least 12 months without any interruptions of greater than 14 consecutive days within the last 1 year, and on a stable regimen that does not include an non-nucleoside reverse transcriptase inhibitor (NNRTI) for at least 4 weeks, without plans to modify ART during the study period.
• Screening plasma HIV RNA levels below the level of quantification on all available determinations in past 24 months.
• Screening CD4+ T-cell count ≥ 500 cells/mm3.

You may not qualify if:

• Subjects receiving a non-nucleoside reverse transcriptase inhibitor
• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
• High-level resistance to both 10-1074 and VRC-07 as defined using the PhenoSense Neutralizing Antibody Assay (Monogram Biosciences).
• Any history of an HIV-associated malignancy, including Kaposi's sarcoma and any type of lymphoma, or virus-associated cancers.
• Active or recent non-HIV-associated malignancy requiring systemic chemotherapy or surgery in the preceding 36 months or for whom such therapies are expected in the subsequent 12 months.
• CD4+ T cell nadir \<350 cells/mm3 during the chronic phase of infection (beginning 6 months following the estimated infection date and confirmed on repeat testing).
• Active hepatitis B (HBV) infection defined as positive HBV surface antigen test.
• \. 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• amfAR, The Foundation for AIDS Research: collaborator
• Ichor Medical Systems Incorporated: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Rockefeller University: collaborator
• Mologen AG: collaborator
• GeoVax, Inc.: collaborator
• International AIDS Vaccine Initiative: collaborator

Study Sites (1)

Zuckerberg San Francisco General Hospital, University of California San Francisco

San Francisco, California, 94110, United States

Location

Related Publications (1)

• 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.

  PMID: 41326736 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Steven Deeks
• Organization: University of California, San Francisco

steven.deeks@ucsf.edu

6282068000

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Residence

Study Record Dates

• First Submitted: April 18, 2020
• First Posted: April 22, 2020
• Study Start: August 1, 2020
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 24, 2026
• Results First Posted: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)