Quantification of Antisense HIV RNA in Patients

Completed

• Conditions: HIV-1-infection
• Interventions: Other: Blood sampling

• Registration Number: NCT05381844
• Lead Sponsor: Institut National de la Santé Et de la Recherche Médicale, France

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.

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 Timeline

• Study First Submitted: 2022-05-16
• Study First Submitted QC: 2022-05-16
• Study First Posted: 2022-05-19
• Study Start: 2022-10-20
• Primary Completion: 2024-10-18
• Study Completion: 2024-10-18
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-10
• Last Update Posted: 2025-03-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
HIV-1-infected, undetectable viral load	Blood sampling	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
HIV-1-infected, untreated	Blood sampling	Patients recently diagnosed with chronic HIV-1-infection with detectable HIV-1 RNA in plasma, sampled before treatment initiation

Primary Outcome Measures

Name	Time	Method
HIV-1 antisense transcripts in PBMCs	30 months	Quantification of total antisense transcripts with quantitative PCR and digital RT-PCR

Secondary Outcome Measures

Name	Time	Method
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
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
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
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.

Trial Locations

Locations (1)

Jean-Paul VIARD; 🇫🇷 Paris, France