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

HIV-1 Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02247687
• Other study ID #: ANRS 161 L-Vir
• Secondary ID: 2014-001663-13
• Status: Terminated
• Phase: Phase 3
• First received: September 9, 2014
• Last updated: October 9, 2015
• Start date: December 2014
• Est. completion date: September 2015

Study information

• Verified date: October 2015
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

Management of participants with low-level persistent viremia

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 (ßHCG) 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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV-1 Infection
• Treatment Resistant Disorders
• Viremia

Intervention

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.
• Isentress® (raltegravir)
• Addition of Isentress® (raltegravir) arm :Isentress® (raltegravir) 400 mg two times a day (BID) added to current antiretroviral treatment with counseling

Other:
• Counseling arm
No change of antiretroviral treatment but only counseling

Locations

Country	Name	City	State
France	Hôpital Avicenne	Bobigny
France	Hôpital Jean Verdier	Bondy
France	Hôpital Pellegrin	Bordeaux
France	Hôpital Saint André	Bordeaux
France	Hôpital de la côte de Nacre	Caen
France	Hôpital Henry Mondor	Creteil
France	Hôpital Européen Georges Pompidou	France
France	Hôpital de Bicêtre	le Kremlin Bicêtre
France	Hôpital de l'Hôtel Dieu	Nantes
France	Hôpital Bichat	Paris
France	Hôpital Cochin	Paris
France	Hôpital Hôtel Dieu	Paris
France	Hôpital Lariboisière	Paris
France	Hôpital Necker	Paris
France	Hôpital pitié Salpetrière	Paris
France	Hôpital Saint Louis	Paris
France	Hôpital Tenon	Paris
France	Hôpital Pontchaillou	Rennes
France	Hôpital Charles Nicoll	Rouen
France	Hôpital Purpan	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)	Janssen-Cilag Ltd.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Proportion of participants with HIV-1 RNA < 50 copies/ml		week 4, week 8, week 12, week 24, week 36, week 48	No
Secondary	Proportion of participants with HIV-1 RNA < 20 copies/ml		week 4, week 8, week 12, week 24, week 36, week 48	No
Secondary	Proportion of participants with HIV-1 RNA <1copy/ml		week 8, week 12, week 24, week 36, week 48	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Levels of antiretroviral drugs in hair	•measurement of concentrations of antiretroviral drugs treatments in hair	day 0, week 12, week 24and end visit	No
Secondary	Levels of HIV-1 RNA in seminal plasma	quantification of HIV RNA in seminal plasma	day 0, week 12, week 48 and end visit	No
Secondary	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	No
Secondary	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	No
Secondary	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	No