First-Line Treatment for HIV-2

HIV-2 Infection Clinical Trial

— FIT-2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02150993
• Other study ID #: ANRS 12294 FIT-2
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: January 26, 2016
• Est. completion date: May 15, 2019

Study information

• Verified date: July 2019
• 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

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 210
• Est. completion date: May 15, 2019
• Est. primary completion date: May 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV-2 Infection

Intervention

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)
• 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)
• 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)

Locations

Country	Name	City	State
Burkina Faso	CHU Sourô Sanou	Bobo-Dioulasso
Burkina Faso	CHU Yalgado Ouedraogo	Ouagadougou
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	CIRBA	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	Abidjan
Senegal	CHNU Fann	Dakar
Togo	ONG Espoirs Vie Togo (EVT)	Lome

Sponsors (1)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Countries where clinical trial is conducted

Burkina Faso,  Côte D'Ivoire,  Senegal,  Togo, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	The evolution of CD4 counts	Evolution of the absolute and percentage CD4 counts during follow-up	between Week 0 and Week 96
Secondary	The evolution of plasma HIV-2 RNA load	Evolution of the plasma viral load during follow-up	between at W0 and W96
Secondary	The observance of antiretroviral treatment	To describe the antiretroviral possession ratio and assessment of compliance by questionnaire	between W0 and W96
Secondary	The resistance mutations profile	Description of new resistance mutations profiles in cases of treatment failure	Weeks 96
Secondary	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
Secondary	The frequency of treatment switches and discontinuations	The frequency of modifications and discontinuations of treatment per arm	between Week 0 and Week 96
Secondary	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

External Links

•   Related Info
•   sponsor site