Quantification of Antisense HIV RNA in Patients

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05381844
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Anticipated Duration (Months): 30
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
HIV-1-infection	Other: Blood sampling

Detailed Description

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

Study Design

• Study Type: Observational
• Anticipated Enrollment: 60 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Quantification of Antisense VIH-1 Transcripts and Comparison in Different Groups of Patients
• Anticipated Study Start Date: Jun 1, 2022
• Anticipated Primary Completion Date: Dec 1, 2024
• Anticipated Study Completion Date: Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
HIV-1-infected, untreated Patients recently diagnosed with chronic HIV-1-infection with detectable HIV-1 RNA in plasma, sampled before treatment initiation	Other: Blood sampling; 30 ml blood sampling for virological research
HIV-1-infected, undetectable viral load 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; 30 ml blood sampling for virological research

Outcome Measures

Primary Outcome Measures

1. HIV-1 antisense transcripts in PBMCs [30 months]

   Quantification of total antisense transcripts with quantitative PCR and digital RT-PCR

Secondary Outcome Measures

1. Correlation between HIV-1 antisense transcripts and HIV-1 DNA in PBMCs [30 months]

   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

2. Correlation between unspliced HIV-1 sense transcripts and HIV-1 DNA in PBMCs [30 months]

   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

3. Correlation between HIV-1 sense and antisense transcripts in PBMCs [30 months]

   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

4. Comparison of untreated patients vs. patients with virological control on treatment. [30 months]

   Study whether the correlations are different in HIV-1-infected persons with ongoing viral replication and persons with virological control on antiretroviral treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jean-Paul VIARD	Paris		France	75004

Sponsors and Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bruner KM, Wang Z, Simonetti FR, Bender AM, Kwon KJ, Sengupta S, Fray EJ, Beg SA, Antar AAR, Jenike KM, Bertagnolli LN, Capoferri AA, Kufera JT, Timmons A, Nobles C, Gregg J, Wada N, Ho YC, Zhang H, Margolick JB, Blankson JN, Deeks SG, Bushman FD, Siliciano JD, Laird GM, Siliciano RF. A quantitative approach for measuring the reservoir of latent HIV-1 proviruses. Nature. 2019 Feb;566(7742):120-125. doi: 10.1038/s41586-019-0898-8. Epub 2019 Jan 30.

• Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
• ClinicalTrials.gov Identifier: NCT05381844
• Other Study ID Numbers: C21-16; 2021-A02266-35
• First Posted: May 19, 2022
• Last Update Posted: May 19, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France: HIV-1

Study Results

No Results Posted as of May 19, 2022