HIV-1-infection
Conditions
Keywords
HIV-1
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
Interventions
OTHERBlood sampling
30 ml blood sampling for virological research
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HIV-1 antisense transcripts in PBMCs | 30 months | Quantification of total antisense transcripts with quantitative PCR and digital RT-PCR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
France
Outcome results
None listed