Clinical trial NCT02247687: Management of Participants With Low-level Persistent Viremia (ANRS 161 L-VIR)
Official title: Management of Participants With Low-level Persistent Viremia (ANRS 161 L-VIR)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: HIV-1 Infection
Treatment Resistant Disorders
Viremia
Keywords: HIV-1
antiretroviral treatment
viral load
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Janssen-Cilag Ltd.
First posted: 2014-09-25
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Management of participants with low-level persistent viremia

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

Eligibility criteria: 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 ...)

Primary outcomes:
measure: Proportion of patients in Virologic success by week 12
timeFrame: week 12
Secondary outcomes:
measure: Proportion of participants with HIV-1 RNA < 50 copies/ml
timeFrame: week 4, week 8, week 12, week 24, week 36, week 48
measure: Proportion of participants with HIV-1 RNA < 20 copies/ml
timeFrame: week 4, week 8, week 12, week 24, week 36, week 48
measure: Proportion of participants with HIV-1 RNA <1copy/ml
timeFrame: week 8, week 12, week 24, week 36, week 48
measure: Change in CD4 cells count from baseline
timeFrame: week 12, week 24, week 48 and end visit
measure: Number of Participants With Virologic Failure and Emergence of Resistance
timeFrame: day 0 and visit at failure time
measure: Quantification of HIV DNA in peripheral blood mononucleated cell (PBMC)
timeFrame: day 0
measure: Levels of antiretroviral drugs in plasma
timeFrame: day 0 and end visit
measure: Levels of antiretroviral drugs in hair
timeFrame: day 0, week 12, week 24and end visit
measure: Levels of HIV-1 RNA in seminal plasma
timeFrame: day 0, week 12, week 48 and end visit
measure: Incidence of Study interruption
timeFrame: From day 0 to week 24
measure: Incidence of clinical and biological adverse events
timeFrame: from day 0 to week 48
measure: Self-reported adherence
timeFrame: day 0, week 4, week 8, week 12, week 24, week 36, week 48 and end visit
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bondy
country: France
facility: Hôpital Jean Verdier
city: Bordeaux
country: France
facility: Hôpital Saint André
city: Bordeaux
country: France
facility: Hôpital Pellegrin
city: Caen
country: France
facility: Hôpital de la côte de Nacre
city: Creteil
country: France
facility: Hôpital Henry Mondor
city: France
country: France
facility: Hôpital Européen Georges Pompidou
city: le Kremlin Bicêtre
country: France
facility: Hôpital de Bicêtre
city: Nantes
country: France
facility: Hôpital de l'Hôtel Dieu
city: Paris
country: France
facility: Hôpital Necker
city: Paris
country: France
facility: Hôpital Tenon
city: Paris
country: France
facility: Hôpital Hôtel Dieu
city: Paris
country: France
facility: Hôpital Lariboisière
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Hôpital pitié Salpetrière
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Bichat
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Rouen
country: France
facility: Hôpital Charles Nicoll
city: Toulouse
country: France
facility: Hôpital Purpan
Study officials:
affiliation: APHP
name: Jade Ghosn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: