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

Suspended

• Conditions: HIV/AIDS
• Interventions: Other: No intervention

• Registration Number: NCT04263207
• Lead Sponsor: Barbara Ensoli, MD, PhD

Brief 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.

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:

1. the persistence of anti-Tat humoral responses;

2. 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 Timeline

• Study Start: 2020-02-04
• Study First Submitted: 2020-02-05
• Study First Submitted QC: 2020-02-07
• Study First Posted: 2020-02-10
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-04
• Last Update Posted: 2024-03-05
• Primary Completion: 2024-12
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
anti-Tat Ab positive subjects	No intervention	-
anti-Tat Ab negative subjects	No intervention	-

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Infectious Dermatology STI Unit San Gallicano Dermatologic Institute , IRCCS; 🇮🇹 Rome, Italy