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

Primary Purpose

HIV Seropositivity

Status

Completed

Phase

Not Applicable

Locations

Italy

Study Type

Interventional

Intervention

Stop of ART

About this trial

This is an interventional other trial for HIV Seropositivity focused on measuring HIV-1

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Ospedale San Raffaele Scientific Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Interruption of antiretroviral therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

Patients who will not resume antiretroviral regimen

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.

Secondary Outcome Measures

Change in plasma viremia

Change in plasma HIV-DNA

Change in CD4+

Change in CD4+/CD8+ ratio

Change in virological biomarkers

Change in virological biomarkers prior to ART interruption and/or at ART resumption

Change in immunological biomarkers

Change in immunological biomarkers prior to ART interruption and/or at ART resumption

Full Information

NCT ID

NCT03198325

First Posted

June 21, 2017

Last Updated

September 11, 2023

Sponsor

Ospedale San Raffaele

1. Study Identification

Unique Protocol Identification Number

NCT03198325

Brief Title

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

Acronym

APACHE

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Completed

Study Start Date

July 27, 2016 (Actual)

Primary Completion Date

December 2017 (Actual)

Study Completion Date

April 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Ospedale San Raffaele

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Seropositivity

Keywords

HIV-1

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Interruption of antiretroviral therapy

Arm Type

Experimental

Arm Description

Intervention Type

Other

Intervention Name(s)

Stop of ART

Intervention Description

Primary Outcome Measure Information:

Title

Patients who will not resume antiretroviral regimen

Description

Time Frame

12 month

Secondary Outcome Measure Information:

Title

Change in plasma viremia

Description

Change in plasma viremia

Time Frame