Clinical trial NCT05381844: Quantification of Antisense HIV RNA in Patients
Official title: Quantification of Antisense VIH-1 Transcripts and Comparison in Different Groups of Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV-1-infection
Keywords: HIV-1
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2022-05-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV-1-infected adults, before treatment, or with undetectable viral load on treatment

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

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

Primary outcomes:
measure: HIV-1 antisense transcripts in PBMCs
timeFrame: 30 months
Secondary outcomes:
measure: Correlation between HIV-1 antisense transcripts and HIV-1 DNA in PBMCs
timeFrame: 30 months
measure: Correlation between unspliced HIV-1 sense transcripts and HIV-1 DNA in PBMCs
timeFrame: 30 months
measure: Correlation between HIV-1 sense and antisense transcripts in PBMCs
timeFrame: 30 months
measure: Comparison of untreated patients vs. patients with virological control on treatment.
timeFrame: 30 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Jean-Paul VIARD
Study officials:
References:
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 HIV disease progression from primary infection. EBioMedicine. 2019 Mar;41:455-464. doi: 10.1016/j.ebiom.2019.02.016. Epub 2019 Feb 23.
citation: 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.