Management of Participants With Low-level Persistent Viremia (ANRS 161 L-VIR)
- Conditions
- HIV-1 InfectionTreatment Resistant DisordersViremia
- Interventions
- Registration Number
- NCT02247687
- Lead Sponsor
- ANRS, Emerging Infectious Diseases
- 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
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 4
- 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)
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Switch arm for protease inhibitor 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. Addition of Isentress® (raltegravir) 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 Counseling arm Counseling arm Counseling without antiretroviral treatment modification
- Primary Outcome Measures
Name Time Method Proportion of patients in Virologic success by week 12 week 12 A virologic success is defined by a patient having plasma HIV-1 RNA levels \<50 copies/ml at weeks 8 and 12.
- Secondary Outcome Measures
Name Time Method 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 <1copy/ml 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 Levels of antiretroviral drugs in plasma day 0 and end visit •plasma concentrations of antiretroviral drugs and correlation with success or failure of the strategy
Levels of antiretroviral drugs in hair day 0, week 12, week 24and end visit •measurement of concentrations of antiretroviral drugs treatments in hair
Levels of HIV-1 RNA in seminal plasma day 0, week 12, week 48 and end visit quantification of HIV RNA in seminal plasma
Change in CD4 cells count from baseline week 12, week 24, week 48 and end visit •Change was calculated as the CD4 count at the corresponding week minus the baseline CD4 count
Quantification of HIV DNA in peripheral blood mononucleated cell (PBMC) day 0 Quantification of HIV DNA in PBMC at day 0 and its association with the proportion of success in each arm
Number of Participants With Virologic Failure and Emergence of Resistance day 0 and visit at failure time •resistance patterns at failure time compared with day 0, in HIV-DNA and in HIV-RNA
Self-reported adherence day 0, week 4, week 8, week 12, week 24, week 36, week 48 and end visit •self-reported percentage of antiretroviral treatment participant had taken during the last 4 weeks
Incidence of Study interruption From day 0 to week 24 •proportion of participants who discontinued the strategy assigned by randomization at day 0 because of failure
Incidence of clinical and biological adverse events from day 0 to week 48 • proportions of participants experiencing a clinical or biological adverse events (ANRS scale)
Trial Locations
- Locations (20)
Hôpital Européen Georges Pompidou
🇫🇷France, France
Hôpital Avicenne
🇫🇷Bobigny, France
Hôpital Jean Verdier
🇫🇷Bondy, France
Hôpital Saint André
🇫🇷Bordeaux, France
Hôpital Pellegrin
🇫🇷Bordeaux, France
Hôpital de la côte de Nacre
🇫🇷Caen, France
Hôpital Henry Mondor
🇫🇷Creteil, France
Hôpital de Bicêtre
🇫🇷le Kremlin Bicêtre, France
Hôpital de l'Hôtel Dieu
🇫🇷Nantes, France
Hôpital Necker
🇫🇷Paris, France
Hôpital Tenon
🇫🇷Paris, France
Hôpital Hôtel Dieu
🇫🇷Paris, France
Hôpital Lariboisière
🇫🇷Paris, France
Hôpital Saint Louis
🇫🇷Paris, France
Hôpital pitié Salpetrière
🇫🇷Paris, France
Hôpital Cochin
🇫🇷Paris, France
Hôpital Pontchaillou
🇫🇷Rennes, France
Hôpital Bichat
🇫🇷Paris, France
Hôpital Charles Nicoll
🇫🇷Rouen, France
Hôpital Purpan
🇫🇷Toulouse, France