Quantification of Antisense HIV RNA in Patients

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

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.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• France
  • Paris, France, 75004
    • Jean-Paul VIARD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

HIV-1-infected adults, before treatment, or with undetectable viral load on treatment

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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

What is the study measuring?

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

Collaborators and Investigators

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

Publications and helpful links

General 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.
• Tremeaux P, Lenfant T, Boufassa F, Essat A, Melard A, Gousset M, Delelis O, Viard JP, Bary M, Goujard C, Rouzioux C, Meyer L, Avettand-Fenoel V; ANRS-SEROCO and PRIMO cohorts. Increasing contribution of integrated forms to total HIV DNA in blood during HIV disease progression from primary infection. EBioMedicine. 2019 Mar;41:455-464. doi: 10.1016/j.ebiom.2019.02.016. Epub 2019 Feb 23.

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Actual): October 18, 2024
• Study Completion (Actual): October 18, 2024

Study Registration Dates

• First Submitted: May 16, 2022
• First Submitted That Met QC Criteria: May 16, 2022
• First Posted (Actual): May 19, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: HIV-1
• Other Study ID Numbers: C21-16; 2021-A02266-35 (Registry Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No