Measurement for Viral Reservoir and Immune Function in HIV-1-infected Patients Under Antiretroviral Therapy

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.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Other: no intervention

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.

• Study Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

• Study Contact: Name: SZU-MIN Hsieh, M.D.; Phone Number: 67736 886-2-23123456; Email: hsmaids@hotmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

HIV-1 infected patients receiving antiretroviral treatment

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Regular treatment; no intervention	Other: no intervention; No intervention
Treatment interruption; no intervention	Other: no intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of Proviral DNA levels	quantitative proviral DNA measurement as the marker of HIV reservoir	The changes of baseline proviral DNA at 48 weeks

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Szu-Min Hsieh, M.D., National Taiwan University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2017
• Primary Completion (Actual): January 21, 2021
• Study Completion (Actual): September 5, 2022

Study Registration Dates

• First Submitted: August 20, 2019
• First Submitted That Met QC Criteria: August 22, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 15, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 201904090RINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No