Management of Participants With Low-level Persistent Viremia (ANRS 161 L-VIR)

Management of participants with low-level persistent viremia

Study Overview

• Status: Terminated
• Conditions: Viremia; HIV-1 Infection; Treatment Resistant Disorders
• Intervention / Treatment: Other: Counseling arm; Drug: Protease inhibitor; Drug: Isentress® (raltegravir)

Detailed Description

ANRS 161 L-Vir is a phase III prospective, randomized, multicenter, open-label, superiority trial for participants with low-level persistent viremia.

Participants will be randomized with a 1:1:1 ratio to the following three arms,

• Reference arm : counseling without antiretroviral treatment modification
• Switch arm : switch of current PI/r for Prezista® (darunavir)/ Norvir® (ritonavir) (switch for a drug with a higher genetic barrier) 600/100 mg two times a day (BID) with counseling.
• Addition of Isentress® (raltégravir) arm : Isentress® (raltegravir) 400 mg two times a day (BID) added to current antiretroviral treatment with counseling

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bobigny, France, 93000
    • Hôpital Avicenne
  • Bondy, France, 93143
    • Hôpital Jean Verdier
  • Bordeaux, France, 33075
    • Hôpital Saint André
  • Bordeaux, France, 33076
    • Hôpital Pellegrin
  • Caen, France, 14033
    • Hôpital de la Côte de Nacre
  • Creteil, France, 94010
    • Hôpital Henry Mondor
  • France, France, 75674
    • Hôpital Européen Georges Pompidou
  • Nantes, France, 44093
    • Hopital de l'Hotel Dieu
  • Paris, France, 75674
    • Hôpital COCHIN
  • Paris, France, 75877
    • Hôpital Bichat
  • Paris, France, 75651
    • Hopital Pitie Salpetriere
  • Paris, France, 75020
    • Hôpital Tenon
  • Paris, France, 75475
    • Hopital Saint Louis
  • Paris, France, 75015
    • Hôpital Necker
  • Paris, France, 75475
    • Hôpital Lariboisière
  • Paris, France, 75181
    • Hôpital Hotel Dieu
  • Rennes, France, 35033
    • Hôpital Pontchaillou
  • Rouen, France, 76031
    • Hôpital Charles Nicoll
  • Toulouse, France, 31059
    • Hopital Purpan
  • le Kremlin Bicêtre, France, 94275
    • Hopital de Bicetre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• HIV-1 infection
• On combined antiretroviral regimen for at least 18 months
• Participant with a stable antiretroviral regimen for at least 6 months, including 2 Reverse-transcriptase inhibitor (INTI) + 1 Boosted Protease Inhibitor IP/r ,
• participant with at least 2 consecutive viral load between 50 and 500 copies/milliliter over the last 9 months (with at least 2 months between the two measurements) quantified with the same commercial kit.
• 50 <or= VL < 500 copies/milliliter at screening visit quantified with the same commercial kit than previous one.
• Participant naïve to raltegravir (RAL)
• failure of amplification or successful realization of genotypic resistance test without evidence for resistance mutations against current treatment (3TC/FTC accepted with M184V mutation)
• creatinin < 3 Upper Limit normal (ULN)
• Aspartate Amino Transférase (ASAT), Alanine Amino Transférase (ALAT) < 5 Upper Limit normal (ULN)
• hemoglobin > 8 g/dL
• platelets > 50 000/mm3
• In women, lack of current pregnancy verified by Beta Human Chorionic Gonadotropin (βHCG) at week -4 visit and use of a mechanical contraceptive method
• Informed consent
• Participants with an active health insurance coverage (article L1121-11 du Code de la Santé Publique)

Exclusion Criteria:

• HIV-2 infection,
• severe medical condition in the last month (inclusion is possible for a stable condition at screening)
• breastfeeding women, current pregnancy or planned pregnancy within 12 months.
• participant currently receiving Prezista® (darunavir)/ Norvir® (ritonavir) (600/100 mg) two times a day (BID) (of note, participants receiving Prezista® (darunavir)/ Norvir® (ritonavir) one time a day (QD) can be included)
• Hypersensitivity Prezista® (darunavir)/ Norvir® (ritonavir) or to any of the excipients of the study treatment
• participant under judicial protection (judicial protection due to temporarily and slightly diminished mental or physical faculties), or under legal guardianship
• planned absence that could prevent the patient from participating in the trial (travel abroad, moving, pending work transfer ...)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Counseling arm; Counseling without antiretroviral treatment modification	Other: Counseling arm; No change of antiretroviral treatment but only counseling
Active Comparator: Switch arm for protease inhibitor; Switch arm for protease inhibitor : intervention is the switch of current boosted protease inhibitor for Prezista® (darunavir)/ Norvir® (ritonavir) (switch for a drug with a higher genetic barrier) 600/100 mg two times a day (BID) with counseling.	Drug: Protease inhibitor; Modification in the antiretroviral treatment •Switch arm for protease inhibitor : intervention switch of current boosted protease inhibitor for Prezista® (darunavir)/ Norvir® (ritonavir) (switch for a drug with a higher genetic barrier) 600/100 mg two times a day (BID) with counseling.; Other Names: Prezista® / Norvir®
Active Comparator: Addition of Isentress® (raltegravir); Drug: Addition of Isentress® (raltegravir) arm • Addition of Isentress® (raltegravir) arm :Isentress® (raltegravir) 400 mg two times a day (BID) added to current antiretroviral treatment with counseling	Drug: Isentress® (raltegravir); • Addition of Isentress® (raltegravir) arm :Isentress® (raltegravir) 400 mg two times a day (BID) added to current antiretroviral treatment with counseling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients in Virologic success by week 12	A virologic success is defined by a patient having plasma HIV-1 RNA levels <50 copies/ml at weeks 8 and 12.	week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with HIV-1 RNA < 50 copies/ml		week 4, week 8, week 12, week 24, week 36, week 48
Proportion of participants with HIV-1 RNA < 20 copies/ml		week 4, week 8, week 12, week 24, week 36, week 48
Proportion of participants with HIV-1 RNA <1copy/ml		week 8, week 12, week 24, week 36, week 48
Change in CD4 cells count from baseline	•Change was calculated as the CD4 count at the corresponding week minus the baseline CD4 count	week 12, week 24, week 48 and end visit
Number of Participants With Virologic Failure and Emergence of Resistance	•resistance patterns at failure time compared with day 0, in HIV-DNA and in HIV-RNA	day 0 and visit at failure time
Quantification of HIV DNA in peripheral blood mononucleated cell (PBMC)	Quantification of HIV DNA in PBMC at day 0 and its association with the proportion of success in each arm	day 0
Levels of antiretroviral drugs in plasma	•plasma concentrations of antiretroviral drugs and correlation with success or failure of the strategy	day 0 and end visit
Levels of antiretroviral drugs in hair	•measurement of concentrations of antiretroviral drugs treatments in hair	day 0, week 12, week 24and end visit
Levels of HIV-1 RNA in seminal plasma	quantification of HIV RNA in seminal plasma	day 0, week 12, week 48 and end visit
Incidence of Study interruption	•proportion of participants who discontinued the strategy assigned by randomization at day 0 because of failure	From day 0 to week 24
Incidence of clinical and biological adverse events	• proportions of participants experiencing a clinical or biological adverse events (ANRS scale)	from day 0 to week 48
Self-reported adherence	•self-reported percentage of antiretroviral treatment participant had taken during the last 4 weeks	day 0, week 4, week 8, week 12, week 24, week 36, week 48 and end visit

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: Janssen-Cilag Ltd.
• Investigators: Principal Investigator: Jade Ghosn, MD, PhD, APHP

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: September 9, 2014
• First Submitted That Met QC Criteria: September 23, 2014
• First Posted (Estimate): September 25, 2014

Study Record Updates

• Last Update Posted (Estimate): October 12, 2015
• Last Update Submitted That Met QC Criteria: October 9, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: HIV-1; antiretroviral treatment; viral load
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Viremia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Viral Protease Inhibitors; Raltegravir Potassium; Protease Inhibitors; HIV Protease Inhibitors
• Other Study ID Numbers: ANRS 161 L-Vir; 2014-001663-13 (EudraCT Number)