HIV/AIDS
Conditions
Keywords
HIV/AIDS, Immune responses, Tat, HIV reservoire, Biomarkers
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.
Interventions
OTHERNo intervention
No intervention
Sponsors
Barbara Ensoli, MD, PhD
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| lymphocytes subset apoptosis | Baseline and through study completion, an average of 3 years | Apoptotic index of isolated lymphocytes subsets |
| 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 \[TZM-bl cell based assay (TZA)\] |
| Inflammation/immune activation biomarkers | Baseline and through study completion, an average of 3 years | Plasma levels of inflammation and immune activation biomarkers |
Countries
Italy
Outcome results
None listed