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CompletedNCT04357821Updated Aug 28, 2026Results posted

Combinatorial Therapy to Induce an HIV Remission

A Phase 1/2 interventional study of Combination Intervention in HIV/AIDS, sponsored by University of California, San Francisco. Completed at 1 site in United States. Open to participants aged 18 Years to 67 Years. Per ClinicalTrials.gov, last updated 2026-08-28.

Sponsored by University of California, San Francisco · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
11
Allocation
Not applicable
Ages
18 Years to 67 Years
Sex
All
01

Study 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).

Read the detailed description

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

  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

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.

02

Conditions studied

  • HIV/AIDS
03

In context

Acquired Immunodeficiency Syndrome

2,040 studies on the registry are indexed under Acquired Immunodeficiency Syndrome; 272 are open to participants now.

This study's enrollment of 11 is below the median of 105 across 1,543 interventional studies indexed under Acquired Immunodeficiency Syndrome.

Browse Acquired Immunodeficiency Syndrome studies →

Lead sponsor

University of California, San Francisco is the lead sponsor of 2,132 studies on the registry; 375 are open to participants now.

Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 67 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria

  1. Willing and able to provide written informed consent.
  2. 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.
  3. Documented HIV-1 infection.
  4. 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.
  5. Screening plasma HIV RNA levels below the level of quantification on all available determinations in past 24 months.
  6. Screening CD4+ T-cell count ≥ 500 cells/mm3.

Key Exclusion Criteria

  1. Subjects receiving a non-nucleoside reverse transcriptase inhibitor
  2. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
  3. High-level resistance to both 10-1074 and VRC-07 as defined using the PhenoSense Neutralizing Antibody Assay (Monogram Biosciences).
  4. Any history of an HIV-associated malignancy, including Kaposi's sarcoma and any type of lymphoma, or virus-associated cancers.
  5. 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.
  6. 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).
  7. Active hepatitis B (HBV) infection defined as positive HBV surface antigen test.

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.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
11 participants (actual)

Study arms

  • Experimental
    Combination intervention arm

    All volunteers will receive the combination intervention outlined above.

    Drug: Combination Intervention

Interventions

  • DrugCombination 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

06

What researchers measure

Primary outcomes

  1. Grade 3 or Greater Adverse Event Count

    Number of participants who experience a new grade 3 or greater adverse event

    Time frame: Week 0 through 102

  2. 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

    Time frame: Week 34 through 86

Secondary outcomes

  1. 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

    Time frame: Week 0 through 62

  2. 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

    Time frame: Week 0 through 86

  3. 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)ɣ+ Gag/CE-specific CD8+ T cell responses. The magnitude was determined based on intracellular cytokine staining (ICS) by measuring the frequency of interferon (IFN)ɣ+ Gag/CE-specific CD8+ T cell responses after 6 hour stimulation with peptide pools matching the CE immunogen.

    Time frame: Week 22

  4. 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)ɣ+ 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.

    Time frame: Week 22

  5. 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.

    Time frame: Baseline to pre-interruption (week 34)

07

Results

Posted Feb 24, 2026
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.

Participant flow

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.

Participant flow — Overall Study
MilestoneCombination Intervention Arm
Started11
Completed10
Not completed1
Withdrew: Investigational product expired .1

Outcome measures

PrimaryGrade 3 or Greater Adverse Event Count

Number of participants who experience a new grade 3 or greater adverse event

Time frame:
Week 0 through 102
Reported as:
Count of participants · Participants
Grade 3 or Greater Adverse Event Count
ParticipantsCombination Intervention Arm
Grade 3 or Greater Adverse Event Count2
PrimaryProportion 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

Time frame:
Week 34 through 86
Reported as:
Count of participants · Participants
Proportion of Participants Achieving Post-treatment Control
ParticipantsCombination Immunotherapy
Proportion of Participants Achieving Post-treatment Control1
SecondaryAny 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

Time frame:
Week 0 through 62
Reported as:
Number · Number of grade 2-4 AEs
Any Grade 2, 3 or 4 Adverse Event Through Week 62
Number of grade 2-4 AEsCombination Intervention Arm
Any Grade 2, 3 or 4 Adverse Event Through Week 62145
SecondaryAny 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

Time frame:
Week 0 through 86
Reported as:
Number · Number of serious adverse events
Any Serious Adverse Events, Medically Attended Adverse Event, and Potentially Immune-mediated Medical Condition
Number of serious adverse eventsCombination Intervention Arm
Any Serious Adverse Events, Medically Attended Adverse Event, and Potentially Immune-mediated Medical Condition3
SecondaryMagnitude 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)ɣ+ Gag/CE-specific CD8+ T cell responses. The magnitude was determined based on intracellular cytokine staining (ICS) by measuring the frequency of interferon (IFN)ɣ+ Gag/CE-specific CD8+ T cell responses after 6 hour stimulation with peptide pools matching the CE immunogen.

Time frame:
Week 22
Reported as:
Median · Percentage of gag INFg+ CD8+ Cells
Magnitude of T Cell Responses
Percentage of gag INFg+ CD8+ CellsCombination Intervention Arm
Magnitude of T Cell Responses0.182 (0.111 to 0.643)
SecondaryBreadth 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)ɣ+ 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.

Time frame:
Week 22
Reported as:
Median · Epitope pools
Breadth of T Cell Responses
Epitope poolsCombination Intervention Arm
Breadth of T Cell Responses5.5 (5 to 7)
SecondaryIntact 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.

Time frame:
Baseline to pre-interruption (week 34)
Reported as:
Mean · Intact genomes/million CD4+ T cells
Intact Provirus DNA Levels
Intact genomes/million CD4+ T cellsCombination Intervention Arm
Intact Provirus DNA Levels1.90 ± 5.20
Post-hocVirologic Rebound

Number of participants who exhibit two consecutive measurements HIV RNA \>200 copies/mL during the analytic treatment interruption

Time frame:
Week 34 to 86
Reported as:
Count of participants · Participants
Virologic Rebound
ParticipantsCombination Intervention Arm
Virologic Rebound9
Post-hocNumber 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

Time frame:
Week 34 to 86
Reported as:
Count of participants · Participants
Number of Participants Resuming Antiretroviral Therapy
ParticipantsCombination Intervention Arm
Number of Participants Resuming Antiretroviral Therapy10
Post-hocAcute Retroviral Rebound

Proportion experiencing any clinically defined episode of acute retroviral syndrome

Time frame:
Week 34 to 86
Reported as:
Count of participants · Participants
Acute Retroviral Rebound
ParticipantsCombination Intervention Arm
Acute Retroviral Rebound0
Post-hocNumber 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)

Time frame:
Week 34 to 86
Reported as:
Count of participants · Participants
Number of Participants With Confirmed Declines in CD4+ T Cell Counts (> 50%)
ParticipantsCombination Intervention Arm
Number of Participants With Confirmed Declines in CD4+ T Cell Counts (> 50%)0

Adverse events

Collected over All adverse events through through Week 102. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Combination Intervention Arm0/11 (0%)3/11 (27.3%)11/11 (100%)
Most frequent serious events
Most frequent serious events
EventCombination Intervention Arm
Elevated ALTHepatobiliary disorders1/11
HypomaniaPsychiatric disorders1/11
Suicide attemptPsychiatric disorders1/11
Most frequent other events
Showing 10 of 57
Most frequent other events
EventCombination Intervention Arm
Injection Site ReactionSkin and subcutaneous tissue disorders11/11
MalaiseGeneral disorders10/11
RashSkin and subcutaneous tissue disorders10/11
Elevated blood pressureCardiac disorders8/11
Non-specific viral infectionInfections and infestations8/11
HeadacheNervous system disorders7/11
NauseaGastrointestinal disorders7/11
ChillsGeneral disorders6/11
DiarrheaGastrointestinal disorders6/11
FatigueGeneral disorders6/11

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Combination Intervention Arm
<=18 years0
Between 18 and 65 years11
>=65 years0
Sex/Gender, Customized
Sex/Gender, Customized(Participants)Combination Intervention Arm
Male10
Female0
Prefer not to state1
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Combination Intervention Arm
White Non-Hispanic6
Hispanic or Latino4
Mixed1
Black or African American0
Asian0
Region of Enrollment
Region of Enrollment(participants)Combination Intervention Arm
United States11
08

Study locations

1 site
  • Zuckerberg San Francisco General Hospital, University of California San Francisco
    San Francisco, California 94110, United States
09

References and documents

Publications

  • 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. PubMed 41326736 ↗

Study documents

  • Protocol and statistical analysis plan · Sep 21, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 28, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04357821
Lead sponsor
University of California, San Francisco
Collaborators
amfAR, The Foundation for AIDS Research, International AIDS Vaccine Initiative, Ichor Medical Systems Incorporated, National Institute of Allergy and Infectious Diseases (NIAID), Rockefeller University, Mologen AG, GeoVax, Inc.
Responsible party
Steven Deeks (Professor in Residence, University of California, San Francisco) — Principal investigator
First posted
Apr 22, 2020
Start date
Aug 1, 2020
Primary completion
Jan 29, 2024
Completion
Jun 12, 2025
Results posted
Feb 24, 2026
Last update
Aug 28, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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