Quantification of Antisense HIV RNA in Patients

NCT ID: NCT05381844

Last Updated: 2025-03-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-10-20
• Study Completion Date: 2024-10-18

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

Conditions

HIV-1-infection

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

HIV-1-infected, untreated

Patients recently diagnosed with chronic HIV-1-infection with detectable HIV-1 RNA in plasma, sampled before treatment initiation

Blood sampling

Intervention Type: OTHER

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

Blood sampling

Intervention Type: OTHER

30 ml blood sampling for virological research

Interventions

Blood sampling

30 ml blood sampling for virological research

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Jean-Paul VIARD

Paris, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 30803934 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30700913 (View on PubMed)

Other Identifiers

2021-A02266-35

Identifier Type: REGISTRY

Identifier Source: secondary_id

C21-16

Identifier Type: -

Identifier Source: org_study_id