Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients (VIH-2)

ANRS 159 VIH-2 : Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients

The HIV-2 is less common ie 1-2 million people in West Africa. HIV-2 does have the same sensitivity to antiretroviral treatment (ART) compared to HIV-1. The ART strategies that are appropriate for the HIV-1 infection are not as effective for HIV-2. Classical triple therapy including PI is less effective for HIV-2. Also, the choice of ARTs in a second line treatment is limited. The first line optimal treatment has to be defined by a prospective and randomized evaluation of other strategies. The primary endpoint will be adapted to the specificity of the HIV-2 infection. The 1st step is to define, with a phase II clinical trial, whether a strategy including 2 NRTIs and raltegravir, as an alternative strategy to the classical triple therapy, shows an immunovirological response, at least, as good as the one obtained with the triple therapy. The hypothesis is that the low ART response observed in HIV-2 infection is due to a low virological strength of the ARTs used and that the combination of 2 NRTIs and raltegravir should show a therapeutic success of at least 50% at week 48.

Study Overview

• Status: Completed
• Conditions: HIV-2 Infection
• Intervention / Treatment: Drug: emtricitabine / tenofovir disoproxil fumarate / raltegravir .

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75018
    • Hopital Bichat-Claude Bernard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age ≥18 years
• HIV-2 mono infection, confirmed by ELISA and Western Blot test or Immunoblot,
• antiretroviral treatment-naive, whatever the duration and indication of prior treatments,
• indication to treatment, with at least one of the following criteria : type B or C events, CD4 lymphocytes count below 500/mm3 at screening-visit or CD4 lymphocytes count decrease of at least 50 cell/µL/year over the last 3 years with the last CD4 lymphocytes count within -/+ 10 % of the nadir, plasma HIV-2 RNA load over or equal to 100 copies/mL at screening-visit,
• Pneumocystis prophylaxis if CD4 lymphocytes count below 200/mm3, combined to a toxoplasmosis prophylaxis in case of a positive toxoplasmosis serology,
• French residency for at least one year,
• Written informed consent, signed by the participant and the investigator (at the latest on the screening-visit and prior any study related intervention)
• Affiliate or beneficiary of a social security system (State Medical Assistance is not a social security scheme).

Exclusion Criteria:

• Absence of effective contraception method(women),
• Pregnancy, breastfeeding or wish for pregnancy during the trial,
• Curative treatment of a progressive opportunistic infection not compatible with those evaluated in the present study,
• Malignant or tumorous affection requiring chemotherapy or radiotherapy,
• Decompensated cirrhosis,
• Viral hepatitis C with a Metavir score over F2,
• Hemoglobinemia below 7g/dL, polynuclear neutrophils below 500/mm3, platelets below 50 000/mm3, creatinine clearance below 50 mL/mn, transaminase, alkaline phosphatase or bilirubin over 2.5N,
• Contraindication to one of the excipients of study treatments,
• Insuline-dependent diabetes mellitus not well controlled (with glycated haemoglobin (HbA1C) over 7%),
• Long-term corticosteroid treatment (more than 3 weeks of treatment),
• Judicial protection, legal guardianship,
• Participation in other therapeutic trial or comprising an exclusion period ongoing at the time of the screening-visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: raltegravir / emtricitabine / tenofovir disoproxil fumarate	Drug: emtricitabine / tenofovir disoproxil fumarate / raltegravir .; emtricitabine : 200 mg/day and tenofovir disoproxil fumarate : 300 mg/day, included in one pill of Truvada® QD. raltegravir : 400 mg x 2/day, 400 mg in one pill of Isentress® BID.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants in Therapeutic Success	The participants will be considered in therapeutic success at Week 48 if they did not present any of the following events: Plasma HIV-2 RNA load over or equal to 100 copies/mL, starting from Week 24 and confirmed within the next 4 weeks,; CD4 lymphocytes gain below 100/mm3 at Week 48 compared to the CD4 lymphocytes counts average between Week-4 and Week 0,; Raltegravir permanent discontinuation,; Death from any cause,; New B or C events confirmed by an endpoint review committee	at Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Change in CD4 Lymphocytes Count at Week 12		between Week 0 and Week 12
Number of Clinical and Biological Events		from Week 0 to Week 48
Median Change of CD4 Lymphocytes at Week 48		between Week 0 and Week 48
Percentage of Patients With Plasma HIV-2 RNA < 40 Copies/mL		between Week 0 and Week 48
Number of Participants With Clinical Progression	Clinical progression is defined as the switch: from category A to B, C or death.; from category B to C or death.	from Week 0 to Week 48
Minimal Observed Percentage of Participants With Moderate to Good Adherence Evaluated With ANRS Self-administered Questionnaire of Adherence		from Week 4 to Week 48
Number of Virological Failure Participants With Resistance Mutations	Virological failure is defined as plasma HIV-2 RNA load over or equal to 100 copies/mL after plasma HIV-2 RNA load below 100copies/mL, confirmed with a retest within the 4 following weeks. The number and type of mutations in the RT and integrase genes compared to week 0 is being reported.	from Week 0 to Week 48
Number of Participants With Treatment Switch or Discontinuation	Overall (regardless of the molecule)	from Week 0 to Week 48
Number of Participants With >6 Copies of HIV-2 DNA in Plasma at Week 48		at Week 48
Minimal Median of the Lower Dimension Out of the 4 Dimensions of the Quality of Life Questionnaire	The quality of life questionnaire is the Professional Quality of Life (PROQOL) questionnaire, including 4 dimensions: Physical health and symptoms, Relationship with others, Mental and cognitive functioning and Treatment impact For each scale, a score ranging from 0 (the worst answer) to 100 (the best answer) is calculated.	from Week 0 to Week 48
Number of Participants With >6 Copies of HIV-2 DNA in Plasma at Week 24		Week 24

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: Merck Sharp & Dohme LLC; Gilead Sciences
• Investigators: Study Chair: Sophie Matheron, Pr, Hopital Bichat-Claude Bernard

Publications and helpful links

General Publications

• Matheron S, Descamps D, Gallien S, Besseghir A, Sellier P, Blum L, Mortier E, Charpentier C, Tubiana R, Damond F, Peytavin G, Ponscarme D, Collin F, Brun-Vezinet F, Chene G; France REcherche Nord&Sud Sida-Hiv Hepatites (ANRS) 159 HIV-2 Trial Study Group. First-line Raltegravir/Emtricitabine/Tenofovir Combination in Human Immunodeficiency Virus Type 2 (HIV-2) Infection: A Phase 2, Noncomparative Trial (ANRS 159 HIV-2). Clin Infect Dis. 2018 Sep 28;67(8):1161-1167. doi: 10.1093/cid/ciy245.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: May 22, 2012
• First Submitted That Met QC Criteria: May 23, 2012
• First Posted (ESTIMATE): May 25, 2012

Study Record Updates

• Last Update Posted (ACTUAL): July 20, 2018
• Last Update Submitted That Met QC Criteria: September 20, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: HIV-2
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Tenofovir; Emtricitabine; Raltegravir Potassium; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: 2011-005038-20; ANRS 159 VIH-2