Monitored Antiretroviral Pause in Chronic HIV-Infected Subjects With Long-Lasting Suppressed Viremia (APACHE)

February 7, 2024 updated by: Castagna Antonella, IRCCS San Raffaele

Monitored Antiretroviral Pause in Chronic HIV-Infected Subjects With Long-Lasting Suppressed Viremia (APACHE Study)

Prospective, open-label, single arm, non-randomized, proof-of-concept study. Eligible patients will sign a written informed consent and will be followed-up at screening, baseline (ART interruption) and at 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.

The study visits will include: general clinical assessment, routine laboratory tests including: creatinine, phosphorus, calcium, alkaline phosphatase, AST, ALT, fasting glucose, total cholesterol, HDL- and LDL-cholesterol, triglycerides, CD4+ cell count and CD4+/CD8+ ratio.

Additional 30 mL of peripheral blood will be withdrawn at study visits for further virological, and immunological investigations and for bio-banking purposes.

During follow-up, the occurrence of two consecutive HIV-1 RNA values >50 copies/mL or the occurrence of stage B or C AIDS-defining events or any serious non-AIDS clinical event at least potentially related to treatment interruption will be criteria for ART resumption.

All patients with HIV-RNA<50 copies/mL at week 48 (end of the study) will resume their baseline ART regimen.

The main demographic, clinical and therapy information will be accurately recorded at the study visits in an electronic Case Report Form.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The aim of this proof-of-concept study on adult (>18 and <65 years old), chronically HIV-1 infected individuals with undetectable viremia for ≥10 years, undetectable HIV-DNA, CD4+≥500 cells/µL and no evidence of detectable residual viremia for ≥5 years is to evaluate the frequency of spontaneous control of virus replication after ART pausing for up to 12 months and to identify the virological and immunological markers associated with spontaneous control of viral replication.

Prospective, open-label, single arm, non-randomized, proof-of-concept study.

Eligible patients will sign a written informed consent and will be followed-up at screening, baseline (ART interruption) and at 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.

The clinical assessment (study visit) will include: the evaluation of CDC stage, height, weight, systolic and diastolic blood pressure and smoking status, routine laboratory tests [including creatinine, phosphorus, calcium, alkaline phosphatase, AST, ALT, fasting glucose, total cholesterol, HDL- and LDL-cholesterol, triglycerides, CD4+ cell count and CD4+/CD8+ ratio, urine analysis].

Additional 30 mL of peripheral blood will be withdrawn at study visits and stored in a biobank for further investigations.

During follow-up, the occurrence of two consecutive HIV-1 RNA values >50 copies/mL or the occurrence of stage B or C AIDS-defining events will be criteria for ART resumption or any serious non-AIDS clinical event at least potentially related to treatment interruption.

All patients with HIV-RNA<50 copies/mL at week 48 (end of the study) will resume their baseline ART regimen.

The main demographic, clinical and therapy information will be accurately recorded at the study visits in an electronic Case Report Form (eCRF).

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Milan, Italy, 20127
        • Ospedale San Raffaele Scientific Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

The study will include HIV-1 infected:

  • men and non-pregnant women,
  • ≥18 and <65 years-old,
  • asking to stop therapy,
  • with HIV-1 RNA<50 copies/mL for ≥10 years,
  • current CD4+≥500 cells/µL,
  • HIV-DNA<100 copies/106PBMCs,
  • no evidence of detectable residual viremia for ≥5 years .

Exclusion Criteria:

The study will exclude HIV-1 infected subjects:

  • significant risk of HIV transmission during IMAP (including evidence of not adopting effective contraception methods and women who wish to be pregnant) in the opinion of the investigator,
  • pregnancy and breastfeeding,
  • a documented pre-ART HIV-1 RNA<200 copies/mL,
  • reactive Hepatitis B virus (HBV) surface antigen,
  • positive HCV-RNA at the time of screening,
  • current AIDS defining event as defined in category C of the 'Centers for disease control and prevention (CDC)' clinical classification,
  • previous diagnosis of diabetes,
  • a previous diagnosis of cancer or major adverse cardiac events (MACE) and currently receiving chemotherapy or immuno-modulating agents at the time of screening,
  • history of HIV-related thrombocytopenia,
  • active renal disease defined as a glomerular filtration rate (calculated by MDRD equation) below 50 mL/min or the presence of HIV associated nephropathy in the past medical history,
  • any condition, including psychiatric or psychological disorders that might interfere with adherence to study requirements or safety of the participant,
  • prior use of any HIV vaccine and/or non-established experimental therapy,
  • active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Interruption of antiretroviral therapy
Patients willing to stop antiretroviral therapy will stop ART.The occurrence of two consecutive HIV-1 RNA values >50 copies/mL or the occurrence of stage B or C AIDS-defining events will be criteria for ART resumption or any serious non-AIDS clinical event at least potentially related to treatment interruption.
Other: Stop of ART
Patients willing to stop antiretroviral therapy will stop ART.The occurrence of two consecutive HIV-1 RNA values >50 copies/mL or the occurrence of stage B or C AIDS-defining events will be criteria for ART resumption or any serious non-AIDS clinical event at least potentially related to treatment interruption.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patients who will not resume antiretroviral regimen
Time Frame: 12 month
Cumulative proportion of patients who will not resume ART 12 months after IMAP (Monitored Antiretroviral Pause) due to the occurrence of two consecutive HIV-1 RNA values >50 copies/mL or the occurrence of stage B or C AIDS-defining events or any serious non-AIDS clinical event at least potentially related to treatment interruption.
12 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in plasma viremia
Time Frame: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.
Change in plasma viremia
1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.
Change in plasma HIV-DNA
Time Frame: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.
Change in plasma HIV-DNA
1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.
Change in CD4+
Time Frame: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.
Change in CD4+
1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.
Change in CD4+/CD8+ ratio
Time Frame: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.
Change in CD4+/CD8+ ratio
1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.
Change in virological biomarkers
Time Frame: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.
Change in virological biomarkers prior to ART interruption and/or at ART resumption
1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.
Change in immunological biomarkers
Time Frame: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.
Change in immunological biomarkers prior to ART interruption and/or at ART resumption
1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 27, 2016

Primary Completion (Actual)

December 1, 2017

Study Completion (Actual)

April 1, 2018

Study Registration Dates

First Submitted

June 21, 2017

First Submitted That Met QC Criteria

June 22, 2017

First Posted (Actual)

June 26, 2017

Study Record Updates

Last Update Posted (Estimated)

February 9, 2024

Last Update Submitted That Met QC Criteria

February 7, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APACHE Study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Congress and scientific pubblications

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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