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HIV SeropositivityAPACHENCT03198325

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

A study testing Stop of ART in people with HIV Seropositivity, run by IRCCS San Raffaele at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
HIV Seropositivity
What is being tested?
Stop of ART
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteItaly
Study dates
27 Jul 2016to Apr 2018
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 .

Who cannot join

  • 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,
Show all 14Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Ospedale San Raffaele Scientific Institute

    Milan, 20127

Other trials in Italy

About this study

Official title: 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.

Read more

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.

Read the 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).

Being tested
Stop of ART
Keywords
HIV-1
Medical subject headings
HIV Seropositivity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Stop of ARTOther

    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.

Study groups in NCT03198325
Study groupRoleWhat they receive
Interruption of antiretroviral therapyExperimentalPatients 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.
Receives: Other: Stop of ART

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 12 month

Secondary outcomes (6)

  1. Change in plasma viremia

    Change in plasma viremia

    Measured: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.

  2. Change in plasma HIV-DNA

    Change in plasma HIV-DNA

    Measured: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.

  3. Change in CD4+

    Change in CD4+

    Measured: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.

  4. Change in CD4+/CD8+ ratio

    Change in CD4+/CD8+ ratio

    Measured: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.

  5. Change in virological biomarkers

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

    Measured: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.

  6. Change in immunological biomarkers

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

    Measured: 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, 48 weeks thereafter or at ART resumption.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jun 2017
  2. Study start27 Jul 2016
  3. Primary completionDec 2017
  4. Study completionApr 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03198325
Sponsor's protocol ID
APACHE Study
Acronym
APACHE
Status last verified
Feb 2024
First submitted
21 Jun 2017
Last updated
9 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Congress and scientific pubblications

Publications

  • Pau AK, George JM. Antiretroviral therapy: current drugs. Infect Dis Clin North Am. 2014 Sep;28(3):371-402. doi: 10.1016/j.idc.2014.06.001.

    PubMed 25151562

  • Strategies for Management of Antiretroviral Therapy (SMART) Study Group; El-Sadr WM, Lundgren J, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, Cohn D, Cooper D, Darbyshire J, Emery S, Fatkenheuer G, Gazzard B, Grund B, Hoy J, Klingman K, Losso M, Markowitz N, Neuhaus J, Phillips A, Rappoport C. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006 Nov 30;355(22):2283-96. doi: 10.1056/NEJMoa062360.

    PubMed 17135583

  • Strategies for Management of Antiretroviral Therapy (SMART) Study Group; Emery S, Neuhaus JA, Phillips AN, Babiker A, Cohen CJ, Gatell JM, Girard PM, Grund B, Law M, Losso MH, Palfreeman A, Wood R. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis. 2008 Apr 15;197(8):1133-44. doi: 10.1086/586713.

    PubMed 18476292

  • Skiest DJ, Krambrink A, Su Z, Robertson KR, Margolis DM; A5170 Study Team. Improved measures of quality of life, lipid profile, and lipoatrophy after treatment interruption in HIV-infected patients with immune preservation: results of ACTG 5170. J Acquir Immune Defic Syndr. 2008 Dec 1;49(4):377-83. doi: 10.1097/QAI.0b013e31818cde21.

    PubMed 18931631

  • Strategies for Management of Antiretroviral Therapy (SMART) Study Group; Lundgren JD, Babiker A, El-Sadr W, Emery S, Grund B, Neaton JD, Neuhaus J, Phillips AN. Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of CD4+ Cell counts and HIV RNA levels during follow-up. J Infect Dis. 2008 Apr 15;197(8):1145-55. doi: 10.1086/529523.

    PubMed 18476293

  • Saez-Cirion A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I, Lecuroux C, Potard V, Versmisse P, Melard A, Prazuck T, Descours B, Guergnon J, Viard JP, Boufassa F, Lambotte O, Goujard C, Meyer L, Costagliola D, Venet A, Pancino G, Autran B, Rouzioux C; ANRS VISCONTI Study Group. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog. 2013 Mar;9(3):e1003211. doi: 10.1371/journal.ppat.1003211. Epub 2013 Mar 14.

    PubMed 23516360

  • Williams JP, Hurst J, Stohr W, Robinson N, Brown H, Fisher M, Kinloch S, Cooper D, Schechter M, Tambussi G, Fidler S, Carrington M, Babiker A, Weber J, Koelsch KK, Kelleher AD, Phillips RE, Frater J; SPARTACTrial Investigators. HIV-1 DNA predicts disease progression and post-treatment virological control. Elife. 2014 Sep 12;3:e03821. doi: 10.7554/eLife.03821.

    PubMed 25217531

  • Ho YC, Shan L, Hosmane NN, Wang J, Laskey SB, Rosenbloom DI, Lai J, Blankson JN, Siliciano JD, Siliciano RF. Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell. 2013 Oct 24;155(3):540-51. doi: 10.1016/j.cell.2013.09.020. Epub 2013 Oct 24.

    PubMed 24243014

  • Hurst J, Hoffmann M, Pace M, Williams JP, Thornhill J, Hamlyn E, Meyerowitz J, Willberg C, Koelsch KK, Robinson N, Brown H, Fisher M, Kinloch S, Cooper DA, Schechter M, Tambussi G, Fidler S, Babiker A, Weber J, Kelleher AD, Phillips RE, Frater J. Immunological biomarkers predict HIV-1 viral rebound after treatment interruption. Nat Commun. 2015 Oct 9;6:8495. doi: 10.1038/ncomms9495.

    PubMed 26449164

  • Lee SA, Bacchetti P, Chomont N, Fromentin R, Lewin SR, O'Doherty U, Palmer S, Richman DD, Siliciano JD, Yukl SA, Deeks SG, Burbelo PD. Anti-HIV Antibody Responses and the HIV Reservoir Size during Antiretroviral Therapy. PLoS One. 2016 Aug 2;11(8):e0160192. doi: 10.1371/journal.pone.0160192. eCollection 2016.

    PubMed 27483366

  • Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange SJ, Siliciano RF. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med. 2003 Jun;9(6):727-8. doi: 10.1038/nm880. Epub 2003 May 18.

    PubMed 12754504

  • Burbelo PD, Lebovitz EE, Notkins AL. Luciferase immunoprecipitation systems for measuring antibodies in autoimmune and infectious diseases. Transl Res. 2015 Feb;165(2):325-35. doi: 10.1016/j.trsl.2014.08.006. Epub 2014 Sep 1.

    PubMed 25241936

  • Assoumou L, Weiss L, Piketty C, Burgard M, Melard A, Girard PM, Rouzioux C, Costagliola D; ANRS 116 SALTO study group. A low HIV-DNA level in peripheral blood mononuclear cells at antiretroviral treatment interruption predicts a higher probability of maintaining viral control. AIDS. 2015 Sep 24;29(15):2003-7. doi: 10.1097/QAD.0000000000000734.

    PubMed 26355572

  • Calin R, Hamimi C, Lambert-Niclot S, Carcelain G, Bellet J, Assoumou L, Tubiana R, Calvez V, Dudoit Y, Costagliola D, Autran B, Katlama C; ULTRASTOP Study Group. Treatment interruption in chronically HIV-infected patients with an ultralow HIV reservoir. AIDS. 2016 Mar 13;30(5):761-9. doi: 10.1097/QAD.0000000000000987.

    PubMed 26730568

  • Cuzin L, Pugliese P, Saune K, Allavena C, Ghosn J, Cottalorda J, Rodallec A, Chaix ML, Fafi-Kremer S, Soulie C, Ouka M, Charpentier C, Bocket L, Mirand A, Guiguet M; Dat'AIDS study group. Levels of intracellular HIV-DNA in patients with suppressive antiretroviral therapy. AIDS. 2015 Aug 24;29(13):1665-71. doi: 10.1097/QAD.0000000000000723.

    PubMed 26372277

Questions about this trial

What is this clinical trial studying?

A study testing Stop of ART in people with HIV Seropositivity, run by IRCCS San Raffaele at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Patients who will not resume antiretroviral regimen (time frame: 12 month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03198325, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2024.

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