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

Study Overview
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Brief Summary
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Management of participants with low-level persistent viremia

Detailed Description
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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

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

Conditions
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Treatment Resistant Disorders, HIV-1 Infection, Viremia

Intervention / Treatment
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* Drug: Protease inhibitor
* Drug: Isentress® (raltegravir)
* Other: Counseling arm


Participation Criteria
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Eligibility Criteria
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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 ...)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Counseling arm<br>Counseling without antiretroviral treatment modification | Other: Counseling arm<br>* No change of antiretroviral treatment but only counseling<br>|
| Active Comparator: Switch arm for protease inhibitor<br>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<br>* 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.<br>* Other names: Prezista® / Norvir®;|
| Active Comparator: Addition of Isentress® (raltegravir)<br>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)<br>* • Addition of Isentress® (raltegravir) arm :Isentress® (raltegravir) 400 mg two times a day (BID) added to current antiretroviral treatment with counseling<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, antiretroviral treatment, viral load