Trial Outcomes & Findings for Trial Evaluating a First Line Combination Therapy With Raltegravir, Emtricitabine and Tenofovir in HIV-2 Infected Patients (NCT NCT01605890)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

at Week 48

Results posted on

2018-07-20

Participant Flow

The study enrolled ART-naïve adults infected with HIV-2 only with history of CDC group B or C event, or a CD4 count \<500 cells/μL, or a CD4 decrease \>50 cells/μL/year over the past 3 years, or a confirmed plasma HIV-2 RNA (pVL) ≥100 copies (cp) /mL from 18 hospital centers in France.The last participant completed in December 2015.

Of the 38 participants screened between July 2012 and January 2015, 30 (78.9%) participants were finally included.

Participant milestones

Participant milestones
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate 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.
Overall Study STARTED	30
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=30 Participants 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.
Age, Categorical <=18 years	0 Participants n=30 Participants
Age, Categorical Between 18 and 65 years	27 Participants n=30 Participants
Age, Categorical >=65 years	3 Participants n=30 Participants
Age, Continuous	48.8 years n=30 Participants
Sex: Female, Male Female	20 Participants n=30 Participants
Sex: Female, Male Male	10 Participants n=30 Participants
Region of Enrollment France	30 participants n=30 Participants

PRIMARY outcome

Timeframe: at Week 48

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

Outcome measures

Outcome measures
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=30 Participants 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.
Percentage of Participants in Therapeutic Success	40 percentage of participants Interval 22.7 to 59.4

SECONDARY outcome

Timeframe: between Week 0 and Week 12

Outcome measures

Outcome measures
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=30 Participants 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.
Median Change in CD4 Lymphocytes Count at Week 12	73 cells/µL Interval 2.0 to 143.0

SECONDARY outcome

Timeframe: from Week 0 to Week 48

Outcome measures

Outcome measures
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=30 Participants 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.
Number of Clinical and Biological Events	61 clinical and biological events

SECONDARY outcome

Timeframe: between Week 0 and Week 48

Outcome measures

Outcome measures
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=28 Participants 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.
Median Change of CD4 Lymphocytes at Week 48	87 cells/µL Interval 38.0 to 213.0

SECONDARY outcome

Timeframe: between Week 0 and Week 48

Outcome measures

Outcome measures
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=28 Participants 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.
Percentage of Patients With Plasma HIV-2 RNA < 40 Copies/mL	96.4 percentage of participants

SECONDARY outcome

Timeframe: from Week 0 to Week 48

Clinical progression is defined as the switch: * from category A to B, C or death. * from category B to C or death.

Outcome measures

Outcome measures
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=30 Participants 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.
Number of Participants With Clinical Progression	0 Participants

SECONDARY outcome

Timeframe: from Week 4 to Week 48

Population: Number of participants with available questionnaire of adherence

Outcome measures

Outcome measures
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=21 Participants 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.
Minimal Observed Percentage of Participants With Moderate to Good Adherence Evaluated With ANRS Self-administered Questionnaire of Adherence	76 percentage of participants

SECONDARY outcome

Timeframe: from Week 0 to Week 48

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.

Outcome measures

Outcome measures
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=30 Participants 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.
Number of Virological Failure Participants With Resistance Mutations	1 Participants

SECONDARY outcome

Timeframe: from Week 0 to Week 48

Overall (regardless of the molecule)

Outcome measures

Outcome measures
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=30 Participants 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.
Number of Participants With Treatment Switch or Discontinuation	4 Participants

SECONDARY outcome

Timeframe: at Week 48

Population: Participants with available measurements

Outcome measures

Outcome measures
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=26 Participants 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.
Number of Participants With >6 Copies of HIV-2 DNA in Plasma at Week 48	3 Participants

SECONDARY outcome

Timeframe: from Week 0 to Week 48

Population: Participants with available PROQOL 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.

Outcome measures

Outcome measures
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=22 Participants 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.
Minimal Median of the Lower Dimension Out of the 4 Dimensions of the Quality of Life Questionnaire	45 Score on a scale Interval 20.0 to 75.0

SECONDARY outcome

Timeframe: Week 24

Population: Participants with available measurement

Outcome measures

Outcome measures
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=24 Participants 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.
Number of Participants With >6 Copies of HIV-2 DNA in Plasma at Week 24	5 Participants

Adverse Events

Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate

Serious events: 4 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=30 participants at risk 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.
Nervous system disorders Lacunar ischemic stroke	3.3% 1/30 • Number of events 1 • 48 weeks
Infections and infestations Helicobacter pylori gastritis, Escherichia coli cystitis	3.3% 1/30 • Number of events 1 • 48 weeks
Respiratory, thoracic and mediastinal disorders Suspected recurrence of bronchopulmonary cancer	3.3% 1/30 • Number of events 1 • 48 weeks
Injury, poisoning and procedural complications Truvada overdose without any adverse event	3.3% 1/30 • Number of events 1 • 48 weeks

Other adverse events

Other adverse events
Measure	Raltegravir / Emtricitabine / Tenofovir Disoproxil Fumarate n=30 participants at risk 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.
Gastrointestinal disorders Nausea	16.7% 5/30 • Number of events 5 • 48 weeks
General disorders Asthenia	13.3% 4/30 • Number of events 4 • 48 weeks
Nervous system disorders Headache	6.7% 2/30 • Number of events 2 • 48 weeks
Gastrointestinal disorders Abdominal pain	6.7% 2/30 • Number of events 2 • 48 weeks
Musculoskeletal and connective tissue disorders Backache	6.7% 2/30 • Number of events 2 • 48 weeks
Infections and infestations Nasopharyngitis	6.7% 2/30 • Number of events 2 • 48 weeks
Blood and lymphatic system disorders Neutropenia	6.7% 2/30 • Number of events 2 • 48 weeks
Blood and lymphatic system disorders Leuco-neutropenia	6.7% 2/30 • Number of events 2 • 48 weeks

Additional Information

Pr Sophie Matheron

Hopital Bichat-Claude Bernard, AP-HP, Paris, France

Phone: +33140257883

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place