ANRS 12372 MODERATO Study

ANRS, Emerging Infectious Diseases480 enrolled

Overview

MODERATO is a phase III, open-label, randomized, multicenter, non-inferiority trial conducted in West and Central Africa (Cameroon, Côte d'Ivoire, Burkina Faso). HIV-1 infected adults receiving first line ART with TDF+XTC+EFV or DTG+XTC+TDF virologically suppressed will be recruited and followed during 100 weeks. The objective is to assess the non-inferiority of a strategy consisting of switching to a dual maintenance therapy (DTG+3TC or ATV/r+3TC), comparing to WHO standard first line regimen (TDF+3TC+EFV or DTG+3TC+TDF), in terms of virological success at 96 weeks

In HIV-1 infected adults receiving first line ART with TDF+XTC+EFV or DTG+XTC+TDF virologically suppressed (viral load \< detection limit of the technique used) for at least two years: to assess the non-inferiority of a strategy consisting of switching to a dual maintenance therapy (DTG+ 3TC or ATV/r+3TC), comparing to WHO standard first line regimen (TDF+3TC+EFV or DTG+3TC+TDF), in terms of virological success at 96 weeks, in Cameroon, Côte d'Ivoire and Burkina Faso. This is a trial including two strategies (dual maintenance therapy and triple reference therapy) and three ART regimens (DTG+3TC and ATV/r+3TC used in the maintenance strategy and TDF+3TC+EFV/ DTG+3TC+TDF used in the reference strategy). The primary analysis will compare the two strategies. Secondary analyses will compare the three ART regimens two by two. In order to make these secondary analyses possible, participants will be randomly assigned, at inclusion, to each of the three ART regimens (arm 1: DTG+3TC; arm 2: ATV/r+3TC; arm 3: TDF+3TC+EFV / DTG+3TC+TDF). The maintenance strategy will include arm 1 and 2. The reference strategy will include arm 3 Number of participants : 480 (160 in each ART regimen, ie 320 in the dual maintenance therapy strategy and 160 in the triple therapy reference strategy) The primary endpoint is treatment success, as defined by using the FDA snapshot algorithm : patients who are still continuing the assigned strategy and whose last available plasma HIV-1 RNA in the the window analysis (90 to 102 weeks) is \<50 copies/ml at the end of the window analysis (90 to 102 weeks)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

480

Conditions

HIV-1-infection

Interventions

dolutegravirDRUG

One daily tablet (50mg) during 96 weeks

atazanavir boosted with ritonavirDRUG

One daily tablet with atazanavir (300 mg) boosted with ritonavir (100 mg) during 96 weeks

tenofovir + lamivudine +efavirenz or dolutegravir + lamivudine + tenofovirDRUG

One daily tablet with tenofovir 245 mg + lamivudine (300 mg) + efavirenz (400 mg) during 96 weeks OR One daily tablet with dolutegravir 50 mg + lamivudine (300 mg) + tenofovir (300 mg) during 96 weeks

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * HIV-1 infection * Age of legal majority * CD4 \> 200 cells/mm3 at pre-inclusion * Start first-line ART with non-nucleotide reverse transcriptase inhibitors including TDF+XTC+EFV for at least two years without a past history of virological failure, OR * Be on TDF+XTC+EFV for at least two years then DTG+XTC+TDF without a past history of virological failure, OR * Be on DTG+XTC+TDF (1st line regimen) for at least two years without a past history of virological failure * Absence of past history of virological failure (viral load above the threshold corresponding to the test used); two blips between 50 and 200 copies/ml are allowed. * At least 2 consecutive HIV-1 RNA \< 50 copies/ml within past 2 years, including HIV-1 RNA at pre-inclusion * Women with pregnancy potential are required to use an effective contraceptive method throughout the study follow up. * Signed informed consent Exclusion Criteria: * HIV-2 infection or HIV-1+2 infection * CD4 nadir \<100 cells/mm3 * Chronic Hepatitis B (HBs Ag positive in the pre-inclusion balance) * Ongoing active Tuberculosis * Ongoing severe opportunistic infection * Ongoing chemotherapy or immunotherapy * Grade \> 2 hemoglobin, neutrophil or platelet disorder * ALT≥ 3 times the upper limit of normal value * Creatinine clearance \< 50 ml/min (CKD-EPI) * Allergy to a trial drugs or drug component * Ongoing pregnancy or Refusal of contraception * Patient at risk of non-compliance * Ongoing treatment with a drug that should not be associated with one of the drugs used in the study (cf appendix E page 77) * Any symptoms or biological findings suggestive of a systemic disorder (renal, hepatic, cardiovascular, pulmonary) or other medical conditions that may interfere with the interpretation of test results or jeopardize the health of patients

Locations (5)

Hôpital de jour, Service des maladies infectieuses, CHU Sourô Sanou

Bobo-Dioulasso, Burkina Faso

Service de médecine interne, CHU Yalgado Ouédraogo

Ouagadougou, Burkina Faso

Service des Maladies Infectieuses, Hôpital du jour, Hôpital Central

Yaoundé, Cameroon

Centre de Prise en Charge et de Formation (CePReF), Association ACONDA

Abidjan, Côte d’Ivoire

Outcomes

Primary Outcomes

The treatment success, as defined by using the FDA snapshot algorithm

Success : The proportion of patients who are still continuing the assigned strategy and whose last available plasma HIV-1 RNA in the the window analysis is \<50 copies/ml at the end of the window analysis. Failure : patients who have discontinued the assigned strategy or whose last available plasma HIV-1 RNA in the window analysis (90 to 102 weeks) is ≥ 50 copies/ml or with no available HIV-1 RNA in the window analysis

Time frame: 90 to 102 weeks

Secondary Outcomes

Failure combined endpoint

Percentage of participants who reach the following combined endpoint : "new drug-resistant resistance mutations observed", "decline of at least 20% in creatinine clearance" and "occurrence of at least one grade 3-4 neuropsychiatric disorder"

Time frame: Between Day 0 and Week 96

Plasma HIV-1 RNA

Evolution of plasma HIV-1 RNA

Time frame: Between Day 0 and Week 96

Virological success

Evolution of the percentage of participants with virological success (VL\< 50 copies/Ml)

Time frame: Between Day 0 and Week 96

CD4 lymphocyte

Evolution of CD4 lymphocyte absolute count and percentage

Time frame: Between Day 0 and Week 96

Virological failure and new resistance mutations

Percentage of participants with virological failure and new resistance mutations

Time frame: Week 48 and Week 96

New HIV-1 drug resistance mutations

Data from ClinicalTrials.gov

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