Clinical trial NCT04068441: Measurement for Viral Reservoir and Immune Function in HIV-1-infected Patients Under Antiretroviral Therapy
Official title: Measurement for Viral Reservoir and Immune Function in HIV-1-infected Patients Under Antiretroviral Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV-1-infection
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2019-08-28
Enrollment: 35
Sex: ALL
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV-1 infected patients receiving antiretroviral treatment

Brief summary: Current antiretroviral therapy (ART) is highly effective to suppress plasma viral load to below the detection limit and to restore the host immunity, thus to prolong the survival of HIV-1-infected patients remarkably. However, HIV-1 will rebound to pre-treatment levels within weeks of interruption or irregular medication. The reason why HIV-1 would not be eradicated by powerful ART can be explained by that the reservoir of latent HIV-1 in resting CD4 T cells will persistently exist even long-term suppression of plasma viral RNA. Several therapeutic approaches that aim to prevent or delay viral rebound after treatment interruption, producing a post-treatment remission or functional cure of HIV-1, are being investigated. This study is to measure the size of viral reservoir and HIV-1-specific T cell response in HIV-1-infected patients during ART to help understand the mechanism of HIV-1 persistence, then to help establish a potential policy for functional cure.

Detailed description: Introduction

Current antiretroviral therapy (ART) is highly effective to suppress plasma viral load to below the detection limit and to restore the host immunity, thus to prolong the survival of HIV-1-infected patients remarkably. However, HIV-1 will rebound to pre-treatment levels within weeks of interruption or irregular medication1,2. The reason why HIV-1 would not be eradicated by powerful ART can be explained by that the reservoir of latent HIV-1 in resting CD4 T cells will persistently exist even long-term suppression of plasma viral RNA. Several therapeutic approaches that aim to prevent or delay viral rebound after treatment interruption, producing a post-treatment remission or functional cure of HIV-1, are being investigated3. This study is to measure the size of viral reservoir and HIV-1-specific T cell response in HIV-1-infected patients during ART to help understand the mechanism of HIV-1 persistence, then to help establish a potential policy for functional cure.

Methods Enrollment criteria

1. Confirmed HIV-1 infected patients under regular follow-up and receiving antiretroviral therapy
2. Men with 20-50 years old

Exclusion criteria

1. Serious co-morbidity
2. Obvious hepatic or renal dysfunction
3. Receiving immunosuppressive therapy

Duration and frequency A total of 48 weeks of follow-up, and laboratory measurement every 8 weeks

Laboratory measurement We will draw the blood specimen from subjects after they sign the informed consent. About 30 mL blood will be taken and sent for the determination of viral reservoir and HIV-1-specific T cell responses, every 8 weeks, from the baseline at enrollment to the end of 48 weeks.

HIV-1 Gag-specific T-cell responses Recombinant HIV-1 Gag p24 (5 ug/mL; Research Diagnostics, Inc.) will be used as HIV-1 antigen. PBMC (106) will be incubated with or without p24 in 24-well plats for 6 days. The frequency of T cells with BrdU incorporation will be measured by flow cytometry.

HIV Viral Reservoirs

Levels and contents of HIV viral reservoirs in the peripheral blood will be analyzed in CD4+ T cells(the major cell type harboring HIV reservoir) in 2 major components:

* Proviral DNA
* Cell-associated (CA) HIV RNAs The quantifications for both HIV pvDNA and CA RNAare based on the PCRbasedquantitative system.

Proviral DNA Assessment The blood samples will be used to isolate CD4+ T cells for cellular DNA extraction.

Standardized aliquot amount of extracted DNA is used to determine HIV pvDNA level throughPCR-based quantitative assay targeting the conserved region of HIV gene. The HIV pvDNAlevel will be presented as copies per million CD4+ T cells.The input cell number is determined by a separate PCR targeting human endogenous gene(s).

Cell-associated (CA) HIV RNA Total cellular RNA will be extracted from CD4+ T cells to generate totalcomplementary DNA (cDNA) through reverse transcription. The cDNA is then used to determine CA HIV RNA level through PCR-based quantitative assay that targets the conserved sequences of HIV at a designated laboratory by Sponsor. The CA RNA level is presented a scopies of endogenous house-keeping gene transcripts, whose copy number will be determined independently by a separate PCR targeting the RNA transcripts of the house-keeping gene.

Eligibility criteria: Inclusion Criteria:

* Confirmed HIV-1-infected patients
* 20-50 years old
* receiving antiretroviral therapy

Exclusion Criteria:

* Serious co-morbidity
* Obvious hepatic or renal dysfunction
* Receiving immunosuppressive therapy

Primary outcomes:
measure: Changes of Proviral DNA levels
timeFrame: The changes of baseline proviral DNA at 48 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Szu-Min Hsieh, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hsieh SM, Pan SC, Huang YS, Chang SC. Reversal of Viral Latency and Induction of Gag-Specific T-Cell Responses in HIV-1-Infected Adults Through Cyclic Treatment Interruption of Rosuvastatin: A Proof-of-Concept Study. J Acquir Immune Defic Syndr. 2021 Apr 1;86(4):500-508. doi: 10.1097/QAI.0000000000002577.