Quantification of Antisense HIV RNA in Patients

Study Overview
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Brief Summary
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The objective of this study is to quantify the expression levels of the HIV-1 unspliced sense transcript and of total HIV-1 antisense transcripts in PBMCs of HIV-1-infected persons, either still untreated or virologically controlled on treatment, and to investigate their correlations with the HIV reservoir as assessed by the quantification of total and integrated HIV-1 DNA.

Detailed Description
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The research team will quantify the expression level of total HIV-1 antisense transcripts in PBMCs from two groups of HIV-1-infected persons: still untreated and virologically controllled on treatment. The research team will also study (i) the correlation between the expression level of total HIV-1 antisense transcripts and the levels of total and integrated HIV-1 DNA in PBMCs, (ii) the correlation between the expression level of the unspliced HIV-1 sense transcript and the levels of total and integrated HIV-1 DNA in PBMCs, (iii) the correlation between the expression levels of total HIV-1 antisense transcripts and the level of the unspliced HIV-1 sense transcript in PBMCs, (iv) whether the correlations are different in the two groups of HIV-1-infected persons : still untreated patients vs. patients with virological control on antiretroviral treatment. Quantification of viral transcripts will rely on quantitative RT-PCRs, yielding the quantity of viral RNAs, normalized on the expression of 2 housekeeping genes, and on a digital RT-PCR, yielding the absolute number of viral RNA copies. The quantification of total and integrated HIV-1 DNA will rely on a quantitative PCR yielding the number of HIV-1 DNA copies/million of PBMCs, according to the technique described in Tremeaux P et al, EBioMedicine 2019;41:455-64. The percentage of intact proviral DNA will be estimated according to the technique described in Bruner KM et al, Nature 2019; 566 :120-5

Official Title
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Quantification of Antisense VIH-1 Transcripts and Comparison in Different Groups of Patients

Conditions
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HIV-1-infection

Intervention / Treatment
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* Other: Blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infection ability to understand the objectives and protocols of the research and to sign the informed consent * group 1 : treatment-naive patients with a detectable HIV-1 viral load Have not received any antiretroviral treatment At the chronic stage as determined during the clinical examination and confirmed by a western blot complete HIV antigens (env bands (gp 120 and 160). + gag and pol bands) with the presence of p31+ *Group 2: patients with chronic HIV-1 infection on antiretroviral therapy efficient Have been on antiretroviral therapy for less than a year With a plasma HIV RNA < 50 copies/mL of blood for at least 6 months Exclusion Criteria: ongoing HIV primary infection coinfection with HIV-2 or HTLV-1/2 ongoing AIDS-defining clinical condition ongoing infectious disease of any type ongoing immunosuppressive treatment incompetent adults, persons under the protection of a conservator, tutor or guardian participation in a trial testing a medication in the 3 months preceding blood sampling pregnant or lactating woman

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV-1-infected, untreated<br>Patients recently diagnosed with chronic HIV-1-infection with detectable HIV-1 RNA in plasma, sampled before treatment initiation | Other: Blood sampling<br>* 30 ml blood sampling for virological research<br>|
| HIV-1-infected, undetectable viral load<br>Patients with chronic HIV-1 infection on antiretroviral treatment for less than a year, with a plasma HIV-1 RNA < 50 copies/ml plasma since at least 6 months | Other: Blood sampling<br>* 30 ml blood sampling for virological research<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV-1 antisense transcripts in PBMCs | Quantification of total antisense transcripts with quantitative PCR and digital RT-PCR | 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between HIV-1 antisense transcripts and HIV-1 DNA in PBMCs | Study of the correlation between the expression level of total HIV-1 antisense transcripts and the level of total and integrated HIV-1 DNA in PBMCs | 30 months | 
| Correlation between unspliced HIV-1 sense transcripts and HIV-1 DNA in PBMCs | Study of the correlation between the expression level of unspliced HIV-1 sense transcripts and the level of total or integrated HIV-1 DNA in PBMCs | 30 months | 
| Correlation between HIV-1 sense and antisense transcripts in PBMCs | Study of the the correlation between the expression level of total HIV-1 antisense transcripts and the level of unspliced HIV-1 sense transcripts in PBMCs | 30 months | 
| Comparison of untreated patients vs. patients with virological control on treatment. | Study whether the correlations are different in HIV-1-infected persons with ongoing viral replication and persons with virological control on antiretroviral treatment. | 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1