Quantification of Antisense HIV RNA in Patients

HIV-1-infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05381844
• Other study ID #: C21-16
• Secondary ID: 2021-A02266-35
• Status: Recruiting
• Start date: October 20, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: December 2022
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: Jean-Paul VIARD, Pr
• Phone: 01 42 34 88 41
• Email: jean-paul.viard[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Other:
• Blood sampling
30 ml blood sampling for virological research

Locations

Country	Name	City	State
France	Jean-Paul VIARD	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

References & Publications (2)

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. — View Citation

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 HI — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HIV-1 antisense transcripts in PBMCs	Quantification of total antisense transcripts with quantitative PCR and digital RT-PCR	30 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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