Clinical trial NCT04263207: Observational Study for the Evaluation of the Role of HIV-1 Tat Protein and Anti-Tat Immune Response In HIV Reservoir
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
Study type: OBSERVATIONAL
Overall status: SUSPENDED
Conditions: HIV/AIDS
Keywords: HIV/AIDS
Immune responses
Tat
HIV reservoire
Biomarkers
Lead sponsor: Istituto Superiore di Sanità
Sponsor class: OTHER
First posted: 2020-02-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV-1 infected adult subjects of either gender, ≥18 years old, under cART, with CD4+ T-cell count ≥250 cells/µL.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: HIV proviral DNA levels
timeFrame: Baseline and through study completion, an average of 3 years
measure: HIV plasma viremia
timeFrame: Baseline and through study completion, an average of 3 years
measure: CD4+ and CD8+ T-cell levels
timeFrame: Baseline and through study completion, an average of 3 years
Secondary outcomes:
measure: lymphocytes subset apoptosis
timeFrame: Baseline and through study completion, an average of 3 years
measure: Induction of replication of competent latent HIV-1 from resting CD4+ T-cell
timeFrame: Baseline and through study completion, an average of 3 years
measure: Inflammation/immune activation biomarkers
timeFrame: Baseline and through study completion, an average of 3 years
measure: Anti-Tat Ab isotypes
timeFrame: Baseline and through study completion, an average of 3 years
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Infectious Dermatology STI Unit San Gallicano Dermatologic Institute , IRCCS
Study officials:
References:
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