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

HIV-2 Infection Clinical Trial

— VIH-2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01605890
• Other study ID #: 2011-005038-20
• Secondary ID: ANRS 159 VIH-2
• Status: Completed
• Phase: Phase 2
• Start date: July 2012
• Est. completion date: December 2015

Study information

• Verified date: September 2017
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-2 Infection

Intervention

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.

Locations

Country	Name	City	State
France	Hôpital Bichat-Claude Bernard	Paris

Sponsors (3)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)	Gilead Sciences, Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Median Change in CD4 Lymphocytes Count at Week 12		between Week 0 and Week 12
Secondary	Number of Clinical and Biological Events		from Week 0 to Week 48
Secondary	Median Change of CD4 Lymphocytes at Week 48		between Week 0 and Week 48
Secondary	Percentage of Patients With Plasma HIV-2 RNA < 40 Copies/mL		between Week 0 and Week 48
Secondary	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
Secondary	Minimal Observed Percentage of Participants With Moderate to Good Adherence Evaluated With ANRS Self-administered Questionnaire of Adherence		from Week 4 to Week 48
Secondary	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
Secondary	Number of Participants With Treatment Switch or Discontinuation	Overall (regardless of the molecule)	from Week 0 to Week 48
Secondary	Number of Participants With >6 Copies of HIV-2 DNA in Plasma at Week 48		at Week 48
Secondary	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
Secondary	Number of Participants With >6 Copies of HIV-2 DNA in Plasma at Week 24		Week 24