HIV-1 Infection, Treatment Resistant Disorders, Viremia
Conditions
Keywords
HIV-1, antiretroviral treatment, viral load
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
Interventions
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.
DRUGIsentress® (raltegravir)
• Addition of Isentress® (raltegravir) arm :Isentress® (raltegravir) 400 mg two times a day (BID) added to current antiretroviral treatment with counseling
OTHERCounseling arm
No change of antiretroviral treatment but only counseling
Sponsors
Janssen-Cilag Ltd.
ANRS, Emerging Infectious Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 ...)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
| 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 |
| 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 |
| Proportion of participants with HIV-1 RNA < 50 copies/ml | week 4, week 8, week 12, week 24, week 36, week 48 | — |
| 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 |
| 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) |
| 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 |
| 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 |
Countries
France
Outcome results
None listed