Clinical trial NCT01605890: Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients
Official title: ANRS 159 VIH-2 : Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-2 Infection
Keywords: HIV-2
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Gilead Sciences
name: Merck Sharp & Dohme LLC
First posted: 2012-05-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants in Therapeutic Success
timeFrame: at Week 48
Secondary outcomes:
measure: Median Change in CD4 Lymphocytes Count at Week 12
timeFrame: between Week 0 and Week 12
measure: Number of Clinical and Biological Events
timeFrame: from Week 0 to Week 48
measure: Median Change of CD4 Lymphocytes at Week 48
timeFrame: between Week 0 and Week 48
measure: Percentage of Patients With Plasma HIV-2 RNA < 40 Copies/mL
timeFrame: between Week 0 and Week 48
measure: Number of Participants With Clinical Progression
timeFrame: from Week 0 to Week 48
measure: Minimal Observed Percentage of Participants With Moderate to Good Adherence Evaluated With ANRS Self-administered Questionnaire of Adherence
timeFrame: from Week 4 to Week 48
measure: Number of Virological Failure Participants With Resistance Mutations
timeFrame: from Week 0 to Week 48
measure: Number of Participants With Treatment Switch or Discontinuation
timeFrame: from Week 0 to Week 48
measure: Number of Participants With >6 Copies of HIV-2 DNA in Plasma at Week 48
timeFrame: at Week 48
measure: Minimal Median of the Lower Dimension Out of the 4 Dimensions of the Quality of Life Questionnaire
timeFrame: from Week 0 to Week 48
measure: Number of Participants With >6 Copies of HIV-2 DNA in Plasma at Week 24
timeFrame: Week 24
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Bichat-Claude Bernard
Study officials:
affiliation: Hopital Bichat-Claude Bernard
name: Sophie Matheron, Pr
role: STUDY_CHAIR
References:
citation: 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.