HIV-1-infectionPhase 2BELIEVENCT05004038
BCG Vaccination Effect on Latent Reservoir Size in Treated HIV-1 Infection:
A Phase 2 study testing BCG Vaccine AJVaccines in people with HIV-1-infection, run by University of Zurich at 1 site in Switzerland.
Trial summary
A phase IIA randomized double-blind placebo-controlled single-centre study of the effect of Bacillus Calmette-Guérin (BCG) vaccination on the HIV latent reservoir Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- BCG Vaccine AJVaccines
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteSwitzerland
- Study dates
- 4 Jan 2022to 1 Sep 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent as documented by signature (see Informed Consent Form),
- Age ≥18 years,
- HIV-1 infection under continuous antiretroviral therapy for ≥1.5 years as requested in the Systems X Cohort,
- Current participation in the Swiss HIV Cohort Study and past participation in the Systems X Cohort.
Who cannot join
- History of virological failure or treatment interruption at any time, defined as HIV-1 viral load >200c/ml at two consecutive measurements at least 4 weeks apart,
- CD4 T-cell count <200/μl at any time or <350/μl during the past 1 year
- Presence of other relevant immunosuppression according to the investigator in addition to HIV (a daily steroid intake of ≥20mg is considered clinically relevant),
- History of or current clinical evidence of active tuberculosis,
- Previous positive tuberculin skin test or tuberculosis INF-gamma release assay (Quantiferon-Test) within the past 10 years,
- Previous BCG-vaccination within the past 10 years,
Show all 9Show fewer
- Known allergy to BCG vaccine or any of its components,
- Documented current febrile illness at screening or in the past 7 days.
- Women who are pregnant or breast-feeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase IIA Randomized Double-blind Placebo-controlled Single-centre Study of the Effect of Bacillus Calmette-Guérin (BCG) Vaccination on the HIV Latent Reservoir
A phase IIA randomized double-blind placebo-controlled single-centre study of the effect of Bacillus Calmette-Guérin (BCG) vaccination on the HIV latent reservoir
Read the detailed description
Background and Rationale:
HIV infection affects around 40 million people globally and is incurable due to persistence of viral genetic material within the host genome as the latent reservoir. Patients within the Swiss HIV Cohort Study with latent tuberculosis were recently shown to have a reduced set point HIV viral load compared to tuberculosis (TB)-naïve individuals. The BCG vaccine has been shown to have wide-ranging immunostimulatory effects and can simulate latent tuberculosis infection.
Objective(s):
The purpose of this study is to characterise potential sustained and clinically relevant effects of the BCG vaccine on the size of the latent HIV-1 reservoir in individuals with stable treated HIV-1 infection with suppressed viremia.
The study seeks primarily to determine the effect of a single dose of the BCG vaccine on the size of the latent HIV-1 viral reservoir over a period of up to 6 months post-administration compared to the size at baseline.
Study design:
Monocentric, randomized, placebo-controlled, stepped-wedge study design with all patients receiving BCG either at baseline or after three months
Measurements and procedures:
Measurement of the HIV-1 latent reservoir using peripheral blood mononuclear cells at three monthly intervals beginning on Day 0.
Study Product / Intervention: Single intradermal application of BCG Vaccine AJVaccines powder for suspension for injection according to the manufacturers' instructions.
Control Intervention: Single intradermal application of 0.1ml of 0.9% saline placebo using an identical procedure.
Number of Participants with Rationale: The study involves 60 participants in total, divided equally between two groups, who will receive early or late administration of the BCG vaccine.
Study Duration: The estimated study duration is 15 months
Statistical Considerations:
In order to power the trial to detect a relevant reduction of the HIV-1 latent reservoir with 90% certainty with a power of 80% at a probability of type 1 error of 5%, we need to enrol 54 patients (based on a paired t-test power calculation assuming the effect size mentioned in Section 10 and the variance of log- total HIV-1 DNA observed by Bachmann et al1). Assuming a drop-out of 10% this implies that 60 patients will be enrolled.
- Conditions
- HIV-1-infection
- Being tested
- BCG Vaccine AJVaccines
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG Vaccine AJVaccinesBiological
Single intradermal injection of BCG Vaccine according to published Summary of Product Characteristics
| Study group | Role | What they receive |
|---|---|---|
| Early Group | Active comparator | We will conduct a randomized, double-blind trial using a stepped-wedge design and involving a total of 60 patients with stable treated HIV and suppressed viral load who will all receive the BCG vaccine during the course of the study. Patients will be divided into two groups of equal size (early and late groups regarding administration of the BCG verum). The trial will be placebo-controlled and double-blind. Patients in the early group will receive the BCG verum at the beginning of Treatment Phase 1, and then the placebo at the beginning of Treatment Phase 2. Receives: Biological: BCG Vaccine AJVaccines |
| Late Group | Active comparator | Patients in the late group will receive placebo at the beginning of Treatment Phase 1 and then the BCG verum at the beginning of Treatment Phase 2. Receives: Biological: BCG Vaccine AJVaccines |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in size of the HIV-1 latent reservoir at 6 months
The primary outcome will be the change in size of the HIV-1 latent reservoir at 6 months post-BCG vaccination compared to pre-vaccination in all patients, with each patient serving as their own control.
This HIV-1 latent reservoir size will be measured as total HIV-1 DNA in peripheral blood mononuclear cells, a well-established and extensively validated marker for the HIV-1 reservoir found to be sensitive, clinically relevant and feasible in larger populations.
Measured: 6 months for each patient
Secondary outcomes (3)
The change in size of the HIV-1 latent reservoir at 3 months
The change in size of the HIV-1 latent reservoir at 3 months post-BCG vaccination compared to 3 months post-placebo (early group versus late group at day 90)
Measured: 3 months for each patient
The change in size of the HIV-1 latent reservoir at 3 months (in all patients) and 9 months (in the early group) post-BCG vaccination compared to pre-vaccination
The change in size of the HIV-1 latent reservoir at 3 months (in all patients) and 9 months (in the early group) post-BCG vaccination compared to pre-vaccination
Measured: 9 months for each patient
The frequency and incidence of adverse events of interest in the verum group compared to the placebo group
The frequency and incidence of adverse events of interest in the verum group compared to the placebo group
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2021
- Study start4 Jan 2022
- Primary completion1 Sep 2023
- Study completion1 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by University of ZurichThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A phase IIA randomized double-blind placebo-controlled single-centre study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Johannes Nemeth, Dr. med., Principal investigator, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05004038
- Sponsor's protocol ID
- 2021-01481
- Acronym
- BELIEVE
- Status last verified
- Apr 2026
- First submitted
- 12 Jul 2021
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
West E, Chaudron SE, Russenberger D, Grube C, Metzner KJ, Neumann K, Tschumi J, Kalin M, Tutumlu TK, Dolle C, Kouyos RD, Gunthard HF, Braun DL, Nemeth J. Safety of Bacillus Calmette-Guerin Vaccination and Impact on HIV-1 Latent Reservoir Size in People With Treated HIV-1 Infection. Open Forum Infect Dis. 2025 Sep 29;12(10):ofaf611. doi: 10.1093/ofid/ofaf611. eCollection 2025 Oct.
PubMed 41127455
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIA Randomized Double-blind Placebo-controlled Single-centre Study of the Effect of Bacillus Calmette-Guérin (BCG) Vaccination on the HIV Latent Reservoir
- ClinicalTrials.gov ID
- NCT05004038
- Acronym / sponsor ID
- BELIEVE / 2021-01481
- Conditions
- HIV-1-infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- 4 Jan 2022 (actual)
- Primary completion
- 1 Sep 2023 (actual)
- Study completion
- 1 Sep 2023 (actual)
- First posted
- 13 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A phase IIA randomized double-blind placebo-controlled single-centre study of the effect of Bacillus Calmette-Guérin (BCG) vaccination on the HIV latent reservoir
Detailed description
Background and Rationale:
HIV infection affects around 40 million people globally and is incurable due to persistence of viral genetic material within the host genome as the latent reservoir. Patients within the Swiss HIV Cohort Study with latent tuberculosis were recently shown to have a reduced set point HIV viral load compared to tuberculosis (TB)-naïve individuals. The BCG vaccine has been shown to have wide-ranging immunostimulatory effects and can simulate latent tuberculosis infection.
Objective(s):
The purpose of this study is to characterise potential sustained and clinically relevant effects of the BCG vaccine on the size of the latent HIV-1 reservoir in individuals with stable treated HIV-1 infection with suppressed viremia.
The study seeks primarily to determine the effect of a single dose of the BCG vaccine on the size of the latent HIV-1 viral reservoir over a period of up to 6 months post-administration compared to the size at baseline.
Study design:
Monocentric, randomized, placebo-controlled, stepped-wedge study design with all patients receiving BCG either at baseline or after three months
Measurements and procedures:
Measurement of the HIV-1 latent reservoir using peripheral blood mononuclear cells at three monthly intervals beginning on Day 0.
Study Product / Intervention: Single intradermal application of BCG Vaccine AJVaccines powder for suspension for injection according to the manufacturers' instructions.
Control Intervention: Single intradermal application of 0.1ml of 0.9% saline placebo using an identical procedure.
Number of Participants with Rationale: The study involves 60 participants in total, divided equally between two groups, who will receive early or late administration of the BCG vaccine.
Study Duration: The estimated study duration is 15 months
Statistical Considerations:
In order to power the trial to detect a relevant reduction of the HIV-1 latent reservoir with 90% certainty with a power of 80% at a probability of type 1 error of 5%, we need to enrol 54 patients (based on a paired t-test power calculation assuming the effect size mentioned in Section 10 and the variance of log- total HIV-1 DNA observed by Bachmann et al1). Assuming a drop-out of 10% this implies that 60 patients will be enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A phase IIA randomized double-blind placebo-controlled single-centre study
| Arm | Type | Receives |
|---|---|---|
| Early Group | Active comparator | Biological: BCG Vaccine AJVaccinesWe will conduct a randomized, double-blind trial using a stepped-wedge design and involving a total of 60 patients with stable treated HIV and suppressed viral load who will all receive the BCG vaccine during the course of the study. Patients will be divided into two groups of equal size (early and late groups regarding administration of the BCG verum). The trial will be placebo-controlled and double-blind. Patients in the early group will receive the BCG verum at the beginning of Treatment Phase 1, and then the placebo at the beginning of Treatment Phase 2. |
| Late Group | Active comparator | Biological: BCG Vaccine AJVaccinesPatients in the late group will receive placebo at the beginning of Treatment Phase 1 and then the BCG verum at the beginning of Treatment Phase 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Informed consent as documented by signature (see Informed Consent Form),
- Age ≥18 years,
- HIV-1 infection under continuous antiretroviral therapy for ≥1.5 years as requested in the Systems X Cohort,
- Current participation in the Swiss HIV Cohort Study and past participation in the Systems X Cohort.
Key exclusion criteria (9 listed)
- History of virological failure or treatment interruption at any time, defined as HIV-1 viral load >200c/ml at two consecutive measurements at least 4 weeks apart,
- CD4 T-cell count <200/μl at any time or <350/μl during the past 1 year
- Presence of other relevant immunosuppression according to the investigator in addition to HIV (a daily steroid intake of ≥20mg is considered clinically relevant),
- History of or current clinical evidence of active tuberculosis,
- Previous positive tuberculin skin test or tuberculosis INF-gamma release assay (Quantiferon-Test) within the past 10 years,
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 |
|---|---|---|
| BCG Vaccine AJVaccinesSingle intradermal injection of BCG Vaccine according to published Summary of Product Characteristics | Biological | Early Group, Late Group |
Primary outcome
Change in size of the HIV-1 latent reservoir at 6 months
Time frame: 6 months for each patient
The primary outcome will be the change in size of the HIV-1 latent reservoir at 6 months post-BCG vaccination compared to pre-vaccination in all patients, with each patient serving as their own control. This HIV-1 latent reservoir size will be measured as total HIV-1 DNA in peripheral blood mononuclear cells, a well-established and extensively validated marker for the HIV-1 reservoir found to be sensitive, clinically relevant and feasible in larger populations.
3 secondary outcomes
The change in size of the HIV-1 latent reservoir at 3 months
Time frame: 3 months for each patient
The change in size of the HIV-1 latent reservoir at 3 months (in all patients) and 9 months (in the early group) post-BCG vaccination compared to pre-vaccination
Time frame: 9 months for each patient
The frequency and incidence of adverse events of interest in the verum group compared to the placebo group
Time frame: 9 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Results publication: PubMed 41127455West E, Chaudron SE, Russenberger D, Grube C, Metzner KJ, Neumann K, Tschumi J, Kalin M, Tutumlu TK, Dolle C, Kouyos RD, Gunthard HF, Braun DL, Nemeth J. Safety of Bacillus Calmette-Guerin Vaccination and Impact on HIV-1 Latent Reservoir Size in People With Treated HIV-1 Infection. Open Forum Infect Dis. 2025 Sep 29;12(10):ofaf611. doi: 10.1093/ofid/ofaf611. eCollection 2025 Oct.
- 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.
Johannes Nemeth, Dr. med. principal investigator
University of Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BCG Vaccine AJVaccines in people with HIV-1-infection, run by University of Zurich at 1 site in Switzerland.
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 4 inclusion and 9 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 6 May 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 Switzerland. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in size of the HIV-1 latent reservoir at 6 months (time frame: 6 months for each patient). 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 NCT05004038, 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 6 May 2026.