HIV/AIDSISS OBS T-005NCT04263207

Observational Study for the Evaluation of the Role of HIV-1 Tat Protein and Anti-Tat Immune Response In HIV Reservoir

An observational study of HIV/AIDS, run by Barbara Ensoli, MD, PhD at 1 site in Italy.

Suspended

Paused. Enrolment is on hold for now and may resume.

Trial summary

A longitudinal observational study in HIV-infected subjects receiving cART addressed to explore the effect of the Tat protein and anti-Tat immunity on the formation and maintenance of HIV-1 virus reservoir. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV/AIDS
How many people: 100 participants
Where: 1 siteItaly
Study dates: 4 Feb 2020to Jun 2025
Phase: Observational
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

Study population: HIV-1 infected adult subjects of either gender, ≥18 years old, under cART, with CD4+ T-cell count ≥250 cells/µL.

Who may be able to join

Age ≥18 years
Diagnosis of HIV-1 infection
To be under cART treatment
CD4+ T-cell count ≥250 cells/microliters
Testing for anti-Tat Ab performed during pre-screening
Signed informed consent

Who cannot join

1. Current therapy with immunomodulators or immunosuppressive drugs or chemotherapy for neoplastic disorders.

Trial locations and contacts

1 site in 1 country.

Italy1 site

Infectious Dermatology STI Unit San Gallicano Dermatologic Institute , IRCCS
Rome, 00144

Other trials in Italy

About this study

Official title: Observational Study for the Evaluation of the Role of HIV-1 Tat Protein and Anti-Tat Immune Response in Peripheral Blood HIV Reservoir Dynamics

Read the detailed description

The study is designed as a longitudinal observational study addressed to identify the effects of Tat protein and humoral/cellular anti-Tat immune responses (induced in the natural infection or by Tat vaccination) in HIV-1 reservoir dynamics in blood of HIV infected patients receiving cART. HIV DNA data will be used for analyzing the decay dynamics.

The primary objective of the study is to determine the rate of decay of total HIV DNA in blood of anti-Tat antibody (Ab) positive versus anti-Tat Ab negative HIV patients receiving cART.

The secondary objectives of the study are to relate the HIV DNA decay data to:

the persistence of anti-Tat humoral responses;
biomarkers of HIV reservoir stability potentially affected by the Tat protein or anti-Tat immune responses, including: i) apoptotic/survival index of CD4+ T cells; ii) reactivation dynamics of latent HIV in resting CD4+ T cells upon exposure to Tat protein and/or activation stimuli; iii) cellular and humoral biomarkers relevant to inflammation and immune dysregulation.

Conditions: HIV/AIDS
Being tested: No intervention
Keywords: HIV/AIDS, Immune responses, Tat, HIV reservoire, Biomarkers
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.

No interventionOther
No intervention

Study groups in NCT04263207
Study group	Role	What they receive
anti-Tat Ab positive subjects		Not described Receives: Other: No intervention
anti-Tat Ab negative subjects		Not described Receives: Other: No intervention

What is being measured

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

HIV proviral DNA levels
Changes of total HIV-1 proviral DNA copies/1.000.000 CD4+ T-cells
Measured: Baseline and through study completion, an average of 3 years
HIV plasma viremia
Changes of HIV plasma viral load (copies/mL)
Measured: Baseline and through study completion, an average of 3 years
CD4+ and CD8+ T-cell levels
Changes of CD4+ and CD8+ T-cell counts (cells/microL)
Measured: Baseline and through study completion, an average of 3 years

Secondary outcomes (4)

lymphocytes subset apoptosis
Apoptotic index of isolated lymphocytes subsets
Measured: Baseline and through study completion, an average of 3 years
Induction of replication of competent latent HIV-1 from resting CD4+ T-cell
Quantification of replication competent latent HIV-1 from isolated resting CD4+ T cells [TZM-bl cell based assay (TZA)]
Measured: Baseline and through study completion, an average of 3 years
Inflammation/immune activation biomarkers
Plasma levels of inflammation and immune activation biomarkers
Measured: Baseline and through study completion, an average of 3 years
Anti-Tat Ab isotypes
Anti-Tat humoral response in terms of anti-Tat IgM, IgG and IgA Ab
Measured: Baseline and through study completion, an average of 3 years

Timeline

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

4 Feb 2020Jun 2025

First posted10 Feb 2020
Study start4 Feb 2020
Primary completionDec 2024 (estimated)
Study completionJun 2025 (estimated)

Why it stopped: Study halted prematurely due to the difficulties in dedicating the human resources necessary to conduct the study deriving from the COVID-19 pandemic, but potentially will resume

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (33)Papers the sponsor has linked to this study.
Other trials for HIV/AIDSStudies of the same condition, open and under way.
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: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 100 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04263207
Sponsor's protocol ID: ISS OBS T-005
Acronym: ISS OBS T-005
Status last verified: Mar 2024
First submitted: 5 Feb 2020
Last updated: 5 Mar 2024
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Murray AJ, Kwon KJ, Farber DL, Siliciano RF. The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence. J Immunol. 2016 Jul 15;197(2):407-17. doi: 10.4049/jimmunol.1600343.
PubMed 27382129
Avettand-Fenoel V, Hocqueloux L, Ghosn J, Cheret A, Frange P, Melard A, Viard JP, Rouzioux C. Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications. Clin Microbiol Rev. 2016 Oct;29(4):859-80. doi: 10.1128/CMR.00015-16.
PubMed 27559075
Blankson JN, Finzi D, Pierson TC, Sabundayo BP, Chadwick K, Margolick JB, Quinn TC, Siliciano RF. Biphasic decay of latently infected CD4+ T cells in acute human immunodeficiency virus type 1 infection. J Infect Dis. 2000 Dec;182(6):1636-42. doi: 10.1086/317615. Epub 2000 Nov 8.
PubMed 11069234
Siliciano JM, Siliciano RF. The Remarkable Stability of the Latent Reservoir for HIV-1 in Resting Memory CD4+ T Cells. J Infect Dis. 2015 Nov 1;212(9):1345-7. doi: 10.1093/infdis/jiv219. Epub 2015 Apr 15. No abstract available.
PubMed 25877551
Ensoli F, Cafaro A, Casabianca A, Tripiciano A, Bellino S, Longo O, Francavilla V, Picconi O, Sgadari C, Moretti S, Cossut MR, Arancio A, Orlandi C, Sernicola L, Maggiorella MT, Paniccia G, Mussini C, Lazzarin A, Sighinolfi L, Palamara G, Gori A, Angarano G, Di Pietro M, Galli M, Mercurio VS, Castelli F, Di Perri G, Monini P, Magnani M, Garaci E, Ensoli B. HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: results of a randomized phase II exploratory clinical trial. Retrovirology. 2015 Apr 29;12:33. doi: 10.1186/s12977-015-0151-y.
PubMed 25924841
Sigal A, Kim JT, Balazs AB, Dekel E, Mayo A, Milo R, Baltimore D. Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy. Nature. 2011 Aug 17;477(7362):95-8. doi: 10.1038/nature10347.
PubMed 21849975
Lorenzo-Redondo R, Fryer HR, Bedford T, Kim EY, Archer J, Pond SLK, Chung YS, Penugonda S, Chipman J, Fletcher CV, Schacker TW, Malim MH, Rambaut A, Haase AT, McLean AR, Wolinsky SM. Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature. 2016 Feb 4;530(7588):51-56. doi: 10.1038/nature16933. Epub 2016 Jan 27.
PubMed 26814962
Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, Lai J, McHugh HL, Hao H, Zhang H, Margolick JB, Gurer C, Murphy AJ, Valenzuela DM, Yancopoulos GD, Deeks SG, Strowig T, Kumar P, Siliciano JD, Salzberg SL, Flavell RA, Shan L, Siliciano RF. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature. 2015 Jan 15;517(7534):381-5. doi: 10.1038/nature14053. Epub 2015 Jan 7.
PubMed 25561180
Hosmane NN, Kwon KJ, Bruner KM, Capoferri AA, Beg S, Rosenbloom DI, Keele BF, Ho YC, Siliciano JD, Siliciano RF. Proliferation of latently infected CD4+ T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics. J Exp Med. 2017 Apr 3;214(4):959-972. doi: 10.1084/jem.20170193. Epub 2017 Mar 24.
PubMed 28341641
Jordan A, Defechereux P, Verdin E. The site of HIV-1 integration in the human genome determines basal transcriptional activity and response to Tat transactivation. EMBO J. 2001 Apr 2;20(7):1726-38. doi: 10.1093/emboj/20.7.1726.
PubMed 11285236
C Quaresma AJ, Bugai A, Barboric M. Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb. Nucleic Acids Res. 2016 Sep 19;44(16):7527-39. doi: 10.1093/nar/gkw585. Epub 2016 Jul 1.
PubMed 27369380
Weinberger LS, Burnett JC, Toettcher JE, Arkin AP, Schaffer DV. Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity. Cell. 2005 Jul 29;122(2):169-82. doi: 10.1016/j.cell.2005.06.006.
PubMed 16051143
Razooky BS, Pai A, Aull K, Rouzine IM, Weinberger LS. A hardwired HIV latency program. Cell. 2015 Feb 26;160(5):990-1001. doi: 10.1016/j.cell.2015.02.009.
PubMed 25723172
Cafaro A, Sgadari C, Picconi O, Tripiciano A, Moretti S, Francavilla V, Pavone Cossut MR, Butto S, Cozzone G, Ensoli F, Monini P, Ensoli B. "cART intensification by the HIV-1 Tat B clade vaccine: progress to phase III efficacy studies". Expert Rev Vaccines. 2018 Feb;17(2):115-126. doi: 10.1080/14760584.2018.1418666. Epub 2017 Dec 22.
PubMed 29243498
Frankel AD, Pabo CO. Cellular uptake of the tat protein from human immunodeficiency virus. Cell. 1988 Dec 23;55(6):1189-93. doi: 10.1016/0092-8674(88)90263-2.
PubMed 2849510

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?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Observational Study for the Evaluation of the Role of HIV-1 Tat Protein and Anti-Tat Immune Response in Peripheral Blood HIV Reservoir Dynamics
ClinicalTrials.gov ID: NCT04263207
Acronym / sponsor ID: ISS OBS T-005 / ISS OBS T-005
Conditions: HIV/AIDS
Keywords: HIV/AIDS, Immune responses, Tat, HIV reservoire, Biomarkers
Study type: Observational
Recruitment status: SuspendedReason stopped: Study halted prematurely due to the difficulties in dedicating the human resources necessary to conduct the study deriving from the COVID-19 pandemic, but potentially will resume
Enrolment: 100 participants (estimated)
Lead sponsor: Barbara Ensoli, MD, PhDUniversity, hospital or other
Study start: 4 Feb 2020 (actual)
Primary completion: Dec 2024 (estimated)
Study completion: Jun 2025 (estimated)
First posted: 10 Feb 2020 (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.

Detailed description

The primary objective of the study is to determine the rate of decay of total HIV DNA in blood of anti-Tat antibody (Ab) positive versus anti-Tat Ab negative HIV patients receiving cART.

The secondary objectives of the study are to relate the HIV DNA decay data to:

the persistence of anti-Tat humoral responses;
biomarkers of HIV reservoir stability potentially affected by the Tat protein or anti-Tat immune responses, including: i) apoptotic/survival index of CD4+ T cells; ii) reactivation dynamics of latent HIV in resting CD4+ T cells upon exposure to Tat protein and/or activation stimuli; iii) cellular and humoral biomarkers relevant to inflammation and immune dysregulation.

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 2

Arm	Type	Receives
anti-Tat Ab positive subjects	–	Other: No intervention
anti-Tat Ab negative subjects	–	Other: No intervention

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: HIV-1 infected adult subjects of either gender, ≥18 years old, under cART, with CD4+ T-cell count ≥250 cells/µL.

Key inclusion criteria (6 listed)

Age ≥18 years
Diagnosis of HIV-1 infection
To be under cART treatment
CD4+ T-cell count ≥250 cells/microliters
Testing for anti-Tat Ab performed during pre-screening

Key exclusion criteria (1 listed)

1. Current therapy with immunomodulators or immunosuppressive drugs or chemotherapy for neoplastic disorders.

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
No interventionNo intervention	Other	anti-Tat Ab negative subjects, anti-Tat Ab positive subjects

Primary outcome

HIV proviral DNA levels
Time frame: Baseline and through study completion, an average of 3 years
Changes of total HIV-1 proviral DNA copies/1.000.000 CD4+ T-cells
HIV plasma viremia
Time frame: Baseline and through study completion, an average of 3 years
Changes of HIV plasma viral load (copies/mL)
CD4+ and CD8+ T-cell levels
Time frame: Baseline and through study completion, an average of 3 years
Changes of CD4+ and CD8+ T-cell counts (cells/microL)

4 secondary outcomes

lymphocytes subset apoptosis
Time frame: Baseline and through study completion, an average of 3 years
Induction of replication of competent latent HIV-1 from resting CD4+ T-cell
Time frame: Baseline and through study completion, an average of 3 years
Inflammation/immune activation biomarkers
Time frame: Baseline and through study completion, an average of 3 years
Anti-Tat Ab isotypes
Time frame: Baseline and through study completion, an average of 3 years

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2024.
Background: PubMed 27382129Murray AJ, Kwon KJ, Farber DL, Siliciano RF. The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence. J Immunol. 2016 Jul 15;197(2):407-17. doi: 10.4049/jimmunol.1600343.
Background: PubMed 27559075Avettand-Fenoel V, Hocqueloux L, Ghosn J, Cheret A, Frange P, Melard A, Viard JP, Rouzioux C. Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications. Clin Microbiol Rev. 2016 Oct;29(4):859-80. doi: 10.1128/CMR.00015-16.
Background: PubMed 11069234Blankson JN, Finzi D, Pierson TC, Sabundayo BP, Chadwick K, Margolick JB, Quinn TC, Siliciano RF. Biphasic decay of latently infected CD4+ T cells in acute human immunodeficiency virus type 1 infection. J Infect Dis. 2000 Dec;182(6):1636-42. doi: 10.1086/317615. Epub 2000 Nov 8.
Background: PubMed 25877551Siliciano JM, Siliciano RF. The Remarkable Stability of the Latent Reservoir for HIV-1 in Resting Memory CD4+ T Cells. J Infect Dis. 2015 Nov 1;212(9):1345-7. doi: 10.1093/infdis/jiv219. Epub 2015 Apr 15. No abstract available.
Background: PubMed 25924841Ensoli F, Cafaro A, Casabianca A, Tripiciano A, Bellino S, Longo O, Francavilla V, Picconi O, Sgadari C, Moretti S, Cossut MR, Arancio A, Orlandi C, Sernicola L, Maggiorella MT, Paniccia G, Mussini C, Lazzarin A, Sighinolfi L, Palamara G, Gori A, Angarano G, Di Pietro M, Galli M, Mercurio VS, Castelli F, Di Perri G, Monini P, Magnani M, Garaci E, Ensoli B. HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: results of a randomized phase II exploratory clinical trial. Retrovirology. 2015 Apr 29;12:33. doi: 10.1186/s12977-015-0151-y.
Background: PubMed 21849975Sigal A, Kim JT, Balazs AB, Dekel E, Mayo A, Milo R, Baltimore D. Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy. Nature. 2011 Aug 17;477(7362):95-8. doi: 10.1038/nature10347.
Background: PubMed 26814962Lorenzo-Redondo R, Fryer HR, Bedford T, Kim EY, Archer J, Pond SLK, Chung YS, Penugonda S, Chipman J, Fletcher CV, Schacker TW, Malim MH, Rambaut A, Haase AT, McLean AR, Wolinsky SM. Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature. 2016 Feb 4;530(7588):51-56. doi: 10.1038/nature16933. Epub 2016 Jan 27.
Background: PubMed 25561180Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, Lai J, McHugh HL, Hao H, Zhang H, Margolick JB, Gurer C, Murphy AJ, Valenzuela DM, Yancopoulos GD, Deeks SG, Strowig T, Kumar P, Siliciano JD, Salzberg SL, Flavell RA, Shan L, Siliciano RF. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature. 2015 Jan 15;517(7534):381-5. doi: 10.1038/nature14053. Epub 2015 Jan 7.
Background: PubMed 28341641Hosmane NN, Kwon KJ, Bruner KM, Capoferri AA, Beg S, Rosenbloom DI, Keele BF, Ho YC, Siliciano JD, Siliciano RF. Proliferation of latently infected CD4+ T cells carrying replication-competent HIV-1: Potential role in latent reservoir dynamics. J Exp Med. 2017 Apr 3;214(4):959-972. doi: 10.1084/jem.20170193. Epub 2017 Mar 24.
Background: PubMed 11285236Jordan A, Defechereux P, Verdin E. The site of HIV-1 integration in the human genome determines basal transcriptional activity and response to Tat transactivation. EMBO J. 2001 Apr 2;20(7):1726-38. doi: 10.1093/emboj/20.7.1726.
Background: PubMed 27369380C Quaresma AJ, Bugai A, Barboric M. Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb. Nucleic Acids Res. 2016 Sep 19;44(16):7527-39. doi: 10.1093/nar/gkw585. Epub 2016 Jul 1.
Background: PubMed 16051143Weinberger LS, Burnett JC, Toettcher JE, Arkin AP, Schaffer DV. Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity. Cell. 2005 Jul 29;122(2):169-82. doi: 10.1016/j.cell.2005.06.006.
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?

An observational study of HIV/AIDS, run by Barbara Ensoli, MD, PhD at 1 site in Italy.

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 1 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: paused, as of the sponsor's last update on 5 Mar 2024. 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 Italy. 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.

Are results available for this study?

Results are not available in the source record.

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?

HIV proviral DNA levels (time frame: Baseline and through study completion, an average of 3 years). The study lists 3 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 NCT04263207, which also lists 33 linked publications.

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 5 Mar 2024; AzTrials last refreshed its copy on 7 Nov 2026.