HIV/AIDSPhase 1/2NCT04357821

Combinatorial Therapy to Induce an HIV Remission

A Phase 1/2 study testing Combination Intervention in people with HIV/AIDS, run by University of California, San Francisco at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 more about this study

Who is it for?: Ages 18 to 67 years
Conditions the study is for: HIV/AIDS
What is being tested?: Combination Intervention
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 11 participants
Where: 1 siteUnited States
Study dates: 1 Aug 2020to 12 Jun 2025
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 67 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.
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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Zuckerberg San Francisco General Hospital, University of California San Francisco
San Francisco, California, 94110

Other trials in United States

About this study

Official title: Combinatorial Therapy With a Therapeutic Conserved Element DNA Vaccine, MVA Vaccine Boost, TLR9 Agonist and Broadly Neutralizing Antibodies: a Proof-of-concept Study Aimed at Inducing an HIV Remission

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

IL-12 adjuvanted p24CE DNA prime (p24CE/IL-12) at Weeks 0 and 4
IL-12 adjuvanted DNA boost (p24CE plus p55gag) at Week 12
MVA/HIV62B (MVA62B) boost at Week 20
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)
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.

Conditions: HIV/AIDS
Being tested: Combination Intervention
Medical subject headings: Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Combination InterventionDrug
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

Study groups in NCT04357821
Study group	Role	What they receive
Combination intervention arm	Experimental	All volunteers will receive the combination intervention outlined above. Receives: Drug: Combination Intervention

What is being measured

The primary outcome is the main question the study is designed to answer.

Grade 3 or Greater Adverse Event Count
Number of participants who experience a new grade 3 or greater adverse event
Measured: 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
Measured: Week 34 through 86

Secondary outcomes (5)

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
Measured: Week 0 through 62
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
Measured: 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)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.
Measured: 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)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.
Measured: 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.
Measured: Baseline to pre-interruption (week 34)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Aug 202012 Jun 2025

First posted22 Apr 2020
Study start1 Aug 2020
Primary completion29 Jan 2024
Study completion12 Jun 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIV/AIDSStudies of the same condition, open and under way.
More trials run by University of California, San FranciscoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 11 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04357821
Sponsor's protocol ID: 18-26957
Other IDs: UM1AI164560
Status last verified: Aug 2026
First submitted: 18 Apr 2020
Last updated: 28 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 28 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Combinatorial Therapy With a Therapeutic Conserved Element DNA Vaccine, MVA Vaccine Boost, TLR9 Agonist and Broadly Neutralizing Antibodies: a Proof-of-concept Study Aimed at Inducing an HIV Remission
ClinicalTrials.gov ID: NCT04357821
Acronym / sponsor ID: 18-26957
Conditions: HIV/AIDS
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 11 participants (actual)
Lead sponsor: University of California, San FranciscoUniversity, hospital or other
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.
Study start: 1 Aug 2020 (actual)
Primary completion: 29 Jan 2024 (actual)
Study completion: 12 Jun 2025 (actual)
First posted: 22 Apr 2020 (actual)
Results: Posted 24 Feb 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

IL-12 adjuvanted p24CE DNA prime (p24CE/IL-12) at Weeks 0 and 4
IL-12 adjuvanted DNA boost (p24CE plus p55gag) at Week 12
MVA/HIV62B (MVA62B) boost at Week 20
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)
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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Combination intervention arm	Experimental	Drug: Combination InterventionAll volunteers will receive the combination intervention outlined above.

Who may qualify

Ages: 18 to 67 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Combination Intervention1. 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	Drug	Combination intervention arm

Primary outcome

Grade 3 or Greater Adverse Event Count
Time frame: Week 0 through 102
Number of participants who experience a new grade 3 or greater adverse event
Proportion of Participants Achieving Post-treatment Control
Time frame: Week 34 through 86
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

5 secondary outcomes

Any Grade 2, 3 or 4 Adverse Event Through Week 62
Time frame: Week 0 through 62
Any Serious Adverse Events, Medically Attended Adverse Event, and Potentially Immune-mediated Medical Condition
Time frame: Week 0 through 86
Magnitude of T Cell Responses
Time frame: Week 22
Breadth of T Cell Responses
Time frame: Week 22
Intact Provirus DNA Levels
Time frame: Baseline to pre-interruption (week 34)

Results and safety

Results posted to the registry on 24 Feb 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Combination Intervention Arm	11	10

Primary outcome: Grade 3 or Greater Adverse Event Count

Time frame: Week 0 through 102. Count of participants. Unit: Participants

Measure	Combination Intervention Arm n = 11
Value	2

Population analysed: All 11 participants who were enrolled

Primary outcome: Proportion of Participants Achieving Post-treatment Control

Time frame: Week 34 through 86. Count of participants. Unit: Participants

Measure	Combination Immunotherapy n = 11
Value	1

Population analysed: Eleven participants were enrolled. One received two vaccines and was disenrolled as future investigational products were going to expire. Ten completed the study.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: All adverse events through through Week 102. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Combination Intervention Arm	3 of 11 (27.3%)	11 of 11 (100%)	0 of 11

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 41326736Peluso 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Combination Intervention in people with HIV/AIDS, run by University of California, San Francisco at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Grade 3 or Greater Adverse Event Count (time frame: Week 0 through 102). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04357821, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2026.