First-Line Treatment for HIV-2 (FIT-2)

A Randomized, Non-comparative, Phase IIb, Unblinded Trial, Evaluating the Efficacy and Safety of Tenofovir-emtricitabine or Lamivudine Plus Zidovudine, Lopinavir/Ritonavir, or Raltegravir, Among ARV-naïve HIV-2 Infected Adult Patients, in West Africa

FIT-2 is a multi-country, phase IIb, randomized, non-comparative study, carried out in West Africa (Côte d'Ivoire, Burkina Faso, Senegal, Togo).

ARV-naïve HIV-2 infected adult patients will be recruited and followed during 96 weeks.

The objective is to evaluate the efficacy and safety of 3 first-line treatments in HIV-2 infected adult patients, in West Africa. A treatment will be considered as effective if more than 55% of patients in that arm attain "global success" at 96 weeks.

Study Overview

• Status: Completed
• Conditions: HIV-2 Infection
• Intervention / Treatment: Drug: Tenofovir + Emtricitabine or Lamivudine + Zidovudine; Drug: Tenofovir + Emtricitabine or Lamivudine + Lopinavir/ritonavir; Drug: Tenofovir + Emtricitabine or Lamivudine + Raltegravir

Detailed Description

Main objective

To determine in treatment-naïve HIV-2 infected patients, with CD4 counts above 200 cells/mm3, which of the following three regimens of first line treatment, Tenofovir (TDF), Emtricitabine or lamivudine (FTC or 3TC) plus Zidovudine (ZDV); TDF-FTC (3TC) plus Lopinavir/ritonavir (LPV / r); or TDF-FTC (3TC) plus raltegravir (RAL), will result in an "global success" rate of > 55% at week 96.

Number of participants : 210

Main outcome :

The proportion of patients with "global success" at W96, defined by survival with a plasma HIV-2 RNA viral load of <50 copies/ml and the non-occurrence of AIDS classified events (excluding tuberculosis) and the non-occurrence of severe morbidities non-AIDS-defining illness (cardiovascular disease, kidney disease, severe bacterial disease) and a delta of CD4 depending on the initial CD4 count (CD4 delta > +100cells/mm3 for initial CD4s between 201 and 500 cells/mm3 or delta ≥0 cells/mm3 for initial CD4s > +500 cells/mm3)

Inclusion criteria:

• Infection by HIV-2 only;
• Age > or = 18 years;
• Naïve for antiretroviral therapy (including antiretroviral treatment in the context of PMTCT except taking a dose of Nevirapine for PMTCT)
• CD4 >200 cells/mm3
• Resident of the city where the study is held or of city suburbs to facilitate participation
• Signed informed consent document

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Burkina Faso
  • Bobo-Dioulasso, Burkina Faso
    • CHU Souro Sanou
  • Ouagadougou, Burkina Faso
    • CHU Yalgado Ouedraogo
• Côte D'Ivoire
  • Abidjan, Côte D'Ivoire
    • CIRBA
  • Abidjan, Côte D'Ivoire
    • Centre de Prise en Charge et de Formation (CePReF), Association ACONDA
  • Abidjan, Côte D'Ivoire
    • Centre Médical du Suivi des Donneurs de Sang (Blood Bank Medical Centre)
  • Abidjan, Côte D'Ivoire
    • o L'Unité de soins ambulatoires et de conseils (USAC), CHU de Treichville
  • Abidjan, Côte D'Ivoire
    • Service des Maladies Infectieuses et Tropicales (SMIT), CHU de Treichville
• Senegal
  • Dakar, Senegal
    • CHNU Fann
• Togo
  • Lome, Togo
    • ONG Espoirs Vie Togo (EVT)

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:

• Infection by HIV-2 only;
• Age > ou = 18 years;
• Naïve for antiretroviral therapy (including antiretroviral treatment in the context of PMTCT except taking a dose of Nevirapine for PMTCT)
• CD4 >200 cells/mm3
• Resident of the city where the study is held or of city suburbs to facilitate participation
• Signed informed consent document

Exclusion Criteria:

• Current participation in any other clinical trial
• Presence of opportunistic non-stabilized infections, of any serious or progressive disease, or of any clinical signs consistent with severe disease whose diagnosis is not yet confirmed, such as fever, weight loss, diarrhea or cough not yet explained (non-exhaustive list).
• All pathology that leads in daily life to prefer one or the other of the three therapeutic regimens for medical reasons or to change the dosages specified in the test. This includes (but not limited to):
• Hemoglobin ≤ 8 g / dL
• Neutrophil count <500 cells/mm3
• Renal impairment with creatinine clearance <50mL/mn
• Blood platelet <50 000 cells/mm3
• Decompensated heart failure
• Hepatic failure Severe (TP<50% or cytolysis severe (ALAT> 3x ULN)
• Active TB during treatment with rifampicin
• Taking drugs that interact with the drugs of the clinical trial (as specified in the SPC)
• Pregnancy, breastfeeding or planning to become pregnant during study follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A : TDF + FTC (or 3TC) + ZDV; Tenofovir + Emtricitabine or Lamivudine + Zidovudine	Drug: Tenofovir + Emtricitabine or Lamivudine + Zidovudine; TDF +FTC or 3TC (Tenofovir disoproxil fumarate 245 mg and emtricitabine 200 mg or lamivudine 300mg) QD (evenings orally with meals) + ZDV (Zidovudine 300 mg) 1 tb BID (mornings and evenings orally); Other Names: TDF+FTC (or 3TC) + ZDV; TDF+FTC (or 3TC) + AZT
Experimental: TDF+FTC (or 3TC) +LPV/r; Tenofovir + Emtricitabine or Lamivudine + Lopinavir/ritonavir	Drug: Tenofovir + Emtricitabine or Lamivudine + Lopinavir/ritonavir; TDF +FTC or 3TC (Tenofovir disoproxil fumarate 245 mg and emtricitabine 200 mg or lamivudine 300mg) QD (evenings orally with meals) + Lop/r (Lopinavir/ritonavir lopinavir 200/50 mg) 2 tbs BID (mornings and evenings orally); Other Names: TDF +FTC (or 3TC) +LPV/r
Experimental: Arm C : TDF +FTC (or 3TC) + RAL; Tenofovir + Emtricitabine or Lamivudine + Raltegravir	Drug: Tenofovir + Emtricitabine or Lamivudine + Raltegravir; TDF +FTC or 3TC (Tenofovir disoproxil fumarate 245 mg and emtricitabine 200 mg or lamivudine 300mg) QD (evenings orally with meals) + RAL (Raltegravir 400 mg) 1 tb BID (mornings and evenings orally); Other Names: TDF +FTC (or 3TC) + RAL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The "overall success"	The proportion of patients with "global success" at W96, defined by survival with a plasma HIV-2 RNA viral load of <50 copies/ml and the non-occurrence of AIDS classified events (excluding tuberculosis) and the non-occurrence of severe morbidities non-AIDS-defining illness (cardiovascular disease, kidney disease, severe bacterial disease) and a delta of CD4 depending on the initial CD4 count (CD4 delta> +100cells/mm3 for initial CD4s between 201 and 500 cells/mm3 or delta ≥0 cells/mm3 for initial CD4s > +500 cells/mm3) A treatment is considered to be effective if the "global success" is > 55 % at 96 weeks.	96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Therapeutic failure	The percentage of patients in "treatment failure" defined by : death or; a delta ≤0 CD4 cells / mm3 between W2 and W24 (or W48) for patients with baseline CD4 between 201 and 500 cells / mm3 or if % of decrease in CD4 > 20% between W2 and W24 (or W48) for patients with baseline CD4 > 500 cellules/mm3 or; a plasma HIV-2 RNA viral load of > or =50 copies/ml or; the occurrence of an AIDS defining event (excluding tuberculosis).	24 weeks
Therapeutic failure	The percentage of patients in "treatment failure" defined by : death or; a delta ≤0 CD4 cells / mm3 between W2 and W24 (or W48) for patients with baseline CD4 between 201 and 500 cells / mm3 or if % of decrease in CD4 > 20% between W0 and W24 (or W48) for patients with baseline CD4 > 500 cellules/mm3 or; a plasma HIV-2 RNA viral load of > or = 50 copies/ml or; the occurrence of an AIDS defining event (excluding tuberculosis).	48 weeks
Incidence and type of severe clinical or biological severe adverse events per arm	Incidence and type of severe clinical or biological severe adverse event (grade 3 or 4)	between Week 0 and Week 96
The clinical progression	The incidence of severe morbidity, defined as: AIDS morbidity, non-AIDS cancer, severe non-AIDS bacterial disease, or any disease leading to death	between Week 0 and Week 96
The evolution of CD4 counts	Evolution of the absolute and percentage CD4 counts during follow-up	between Week 0 and Week 96
The evolution of plasma HIV-2 RNA load	Evolution of the plasma viral load during follow-up	between at W0 and W96
The observance of antiretroviral treatment	To describe the antiretroviral possession ratio and assessment of compliance by questionnaire	between W0 and W96
The resistance mutations profile	Description of new resistance mutations profiles in cases of treatment failure	Weeks 96
The evolution of the HIV-2 DNA titers in PBMC	To describe the evolution the HIV-2 DNA titers in PBMC	between Week 0 and Week 96
The frequency of treatment switches and discontinuations	The frequency of modifications and discontinuations of treatment per arm	between Week 0 and Week 96
To model the long-term survival and cost-effectiveness ratio	The probability of survival and the incremental cost-effectiveness of these three treatment regimens	Weeks 96

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Investigators: Principal Investigator: Serge P. Eholié, MD, MSc, Pr, Service des Maladies Infectieuses et Tropicales, CHU de Treichville, Abidjan, Côte d'Ivoire; Principal Investigator: Françoise P. Brun-Vézinet, MD, MSc, Pr, Laboratoire de virologie, Hôpital Bichat-Claude Bernard

Publications and helpful links

Helpful Links

• sponsor site
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2016
• Primary Completion (Actual): May 15, 2019
• Study Completion (Actual): May 15, 2019

Study Registration Dates

• First Submitted: May 28, 2014
• First Submitted That Met QC Criteria: May 29, 2014
• First Posted (Estimate): May 30, 2014

Study Record Updates

• Last Update Posted (Actual): July 22, 2019
• Last Update Submitted That Met QC Criteria: July 19, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Adults; Africa; Antiretroviral Treatment; HIV-2; firsts line ART
• 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; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Raltegravir Potassium; Ritonavir; Lopinavir; Lamivudine; Zidovudine; Lamivudine, zidovudine drug combination
• Other Study ID Numbers: ANRS 12294 FIT-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No