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

Phase 3TerminatedNCT02247687

ANRS, Emerging Infectious Diseases4 enrolled

Overview

Management of participants with low-level persistent viremia

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HIV-1 Infection Treatment Resistant Disorders Viremia

Interventions

Protease inhibitorDRUG

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)DRUG

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

Counseling armOTHER

No change of antiretroviral treatment but only counseling

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 ...)

Locations (20)

Hôpital Avicenne

Bobigny, France

Hôpital Jean Verdier

Bondy, France

Outcomes

Primary Outcomes

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.

Time frame: week 12

Secondary Outcomes

Proportion of participants with HIV-1 RNA < 50 copies/ml

Time frame: week 4, week 8, week 12, week 24, week 36, week 48

Proportion of participants with HIV-1 RNA < 20 copies/ml

Time frame: week 4, week 8, week 12, week 24, week 36, week 48

Proportion of participants with HIV-1 RNA <1copy/ml

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: day 0

Levels of antiretroviral drugs in plasma

•plasma concentrations of antiretroviral drugs and correlation with success or failure of the strategy

Data from ClinicalTrials.gov

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