Evaluation of Three Strategies of Second-line Antiretroviral Treatment in Africa (Dakar - Bobo-Dioulasso - Yaoundé) (2LADY)
Primary Purpose
HIV, HIV Infections
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)
Sponsored by
About this trial
This is an interventional treatment trial for HIV focused on measuring HIV, Second line treatment, WHO recommendations, Africa, Treatment strategies, treatment experienced
Eligibility Criteria
Inclusion Criteria:
- Patient over the age of 18 years at pre-inclusion and monitored under outpatient conditions
- Documented HIV-1 infection regardless of clinical stage and CD4 lymphocyte count
- Patient with treatment failure after first-line antiretroviral treatment with a combination including a non-nucleoside reverse transcriptase inhibitor and two nucleoside reverse transcriptase inhibitors, failure being defined as 2 measurements (at 1 month interval) of plasma HIV RNA levels > 1000 copies/ml after at least 6 months of uninterrupted treatment
- Adherence (> 80%) to first- line antiretroviral treatment (questionnaire) at pre inclusion
- Patient agrees not to take any concomitant medication during the trial without informing the investigator
- Informed consent signed no later than D-15
- For women in childbearing age: negative pregnancy test at inclusion, with no plan of pregnancy in the coming 12 months and agreeing to use mechanical contraception (with or without hormonal contraception) during the study
Exclusion Criteria:
- Infection with HIV-2 or HIV-1 groups O or N or HIV1+2
- Deficiency of the patient, making it difficult, if not impossible, for him/her to take part in the trial or understand the information provided to him/her
- Participation in any other clinical trial
- Presence of an uncontrolled, ongoing opportunistic infection or of any severe or progressive disease
- First-line treatment with a protease inhibitor, abacavir, tenofovir or ddI
- Ongoing treatment with rifampicin
- Severe hepatic insufficiency (TP < 50%)
- ALAT > 3 x ULN
- Creatinine clearance calculated by Cockcroft formula < 50 ml/min
- Hb ≤ 8 g/dl
- Platelets < 50,000 cells/mm3
- Neutrophiles < 500 cells/ mm3
- Use of drugs prohibited in the context of this trial (drugs contraindicated by the SCP of the trial drugs) - in the event of tuberculosis or malaria during the trial, a list of authorized medicines and, if necessary, a dose adjustment of the antiretroviral medication will be provided
- Pregnancy or lactation
Sites / Locations
- Day Hospital, CHU Sanou Souro
- Day Hospital, Central Hospital
- Clinical Research and Training Center, Fann Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Arm A
Arm B
Arm C
Arm Description
emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)
Outcomes
Primary Outcome Measures
Number of Patients With Plasma HIV RNA < 50 Copies/mL
Secondary Outcome Measures
Number of Patients With WHO Stage 3 and 4 HIV Related Events
patients having a diagnosis of HIV related event classified as stage 3 or 4
Patients With Plasma HIV RNA < 200 Copies/ml
number of patients with plasma HIV RNA below 200 copies/ml
Gain in CD4 Cells Between Baseline and W48
median gain in circulating CD4 cells between baseline and W48
Number of Patients Discontinuing Study Treatment
number of patients discounting treatment because of adverse events
Tolerance: Gastrointestinal Complains
Gastrointestinal complaints (grade 1 to 4) between baseline and W48.
Tolerance: Neuropathies (Grade 1 to 4)
any symptom of peripheral neuropathy
Tolerance: Equal or Superior to a 25% Reduction in eGFR (Glomerular Filtration Rate)
evaluation of estimated glomerular filtration rate and number of participant with a decrease equal or superior to 25% of the baseline value
Adherence
number of patients in different categories of adherence as measured by questionnaire
Number of Patients With Resistance Mutations
number of patients with resistance mutations after second line treatment failure (HIV RNA> 1000 copies/ml)
Development of Metabolic Syndrome
number of patients developing metabolic syndrome over a period of 48 weeks
Number of Patients With HIV Plasma Viral Load < 50 Copies/ml
Snapshot of patients with HIV viral load less then 50 copies/ml at week 24
Number of Patients With HIV Plasma Viral Load < 200 Copies/ml
number of patients having a plasma viral load below 200 copies/ml at week 24
Full Information
NCT ID
NCT00928187
First Posted
June 23, 2009
Last Updated
January 12, 2017
Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Gilead Sciences, Janssen Pharmaceutica
1. Study Identification
Unique Protocol Identification Number
NCT00928187
Brief Title
Evaluation of Three Strategies of Second-line Antiretroviral Treatment in Africa (Dakar - Bobo-Dioulasso - Yaoundé)
Acronym
2LADY
Official Title
Multicentric, Non-inferiority, Randomized, Non-blinded Phase 3 Trial Comparing Virological Response at 48 Weeks of 3 Antiretroviral Treatment Regimens in HIV-1-infected Patients With Treatment Failure After 1st Line Antiretroviral Therapy (Cameroon, Burkina Faso, Senegal)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
November 2009 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
December 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
Gilead Sciences, Janssen Pharmaceutica
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Since the first line antiretroviral (ARV) treatment is now largely accessible in the Sub-Saharian Africa countries, documentation of virological failure, drug resistance patterns and second line treatment evaluation are still to be consolidated in settings where viral load monitoring is not available and non-B HIV subtype is predominant.
This trial aims at evaluating the efficacy and tolerance of 3 different second line treatment strategies: two recommended by WHO combine two non-nucleoside reverse transcriptase inhibitor associated with a ritonavir boosted protease inhibitor (emtricitabine-tenofovir-lopinavir/ritonavir and abacavir-didanosine-lopinavir/ritonavir); the third strategy combines emtricitabine-tenofovir-darunavir/ritonavir and is not yet evaluated in Sub-Saharian Africa. Darunavir has a potentially superior antiviral efficacy, a better tolerance and its single daily administration may facilitate treatment adherence.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV, HIV Infections
Keywords
HIV, Second line treatment, WHO recommendations, Africa, Treatment strategies, treatment experienced
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
454 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Active Comparator
Arm Description
emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
Arm Title
Arm C
Arm Type
Active Comparator
Arm Description
emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)
Intervention Type
Drug
Intervention Name(s)
emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
Intervention Description
Emtricitabine 200 mg/tenofovir 300 mg 1 tablet/day with food + Lopinavir 200 mg/Ritonavir 50 mg 2 tablets in the morning and 2 tablets in the evening
Intervention Type
Drug
Intervention Name(s)
abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
Intervention Description
Didanosine 1 entero-coated capsule/day in fasting conditions (dosage 250 mg if weight < 60 kg, 400 mg if weight > 60 kg) + abacavir 300 mg 1 tablet in the morning and in the evening + Lopinavir 200 mg/Ritonavir 50 mg 2 tablets morning and evening
Intervention Type
Drug
Intervention Name(s)
emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)
Intervention Description
Emtricitabine 200 mg/tenofovir 300 mg 1 tablet/day with food + darunavir 400 mg 2 tablets + ritonavir 100 mg 1 capsule, in a single dose with food
Primary Outcome Measure Information:
Title
Number of Patients With Plasma HIV RNA < 50 Copies/mL
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Number of Patients With WHO Stage 3 and 4 HIV Related Events
Description
patients having a diagnosis of HIV related event classified as stage 3 or 4
Time Frame
between baseline and 48 weeks
Title
Patients With Plasma HIV RNA < 200 Copies/ml
Description
number of patients with plasma HIV RNA below 200 copies/ml
Time Frame
48 weeks
Title
Gain in CD4 Cells Between Baseline and W48
Description
median gain in circulating CD4 cells between baseline and W48
Time Frame
between baseline and 48 weeks
Title
Number of Patients Discontinuing Study Treatment
Description
number of patients discounting treatment because of adverse events
Time Frame
between baseline and W48
Title
Tolerance: Gastrointestinal Complains
Description
Gastrointestinal complaints (grade 1 to 4) between baseline and W48.
Time Frame
between baseline and 48 weeks
Title
Tolerance: Neuropathies (Grade 1 to 4)
Description
any symptom of peripheral neuropathy
Time Frame
between baseline and W48
Title
Tolerance: Equal or Superior to a 25% Reduction in eGFR (Glomerular Filtration Rate)
Description
evaluation of estimated glomerular filtration rate and number of participant with a decrease equal or superior to 25% of the baseline value
Time Frame
between baseline and W48
Title
Adherence
Description
number of patients in different categories of adherence as measured by questionnaire
Time Frame
between baseline and W48
Title
Number of Patients With Resistance Mutations
Description
number of patients with resistance mutations after second line treatment failure (HIV RNA> 1000 copies/ml)
Time Frame
between W12 and W48
Title
Development of Metabolic Syndrome
Description
number of patients developing metabolic syndrome over a period of 48 weeks
Time Frame
from baseline to week 48
Title
Number of Patients With HIV Plasma Viral Load < 50 Copies/ml
Description
Snapshot of patients with HIV viral load less then 50 copies/ml at week 24
Time Frame
Week 24
Title
Number of Patients With HIV Plasma Viral Load < 200 Copies/ml
Description
number of patients having a plasma viral load below 200 copies/ml at week 24
Time Frame
Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient over the age of 18 years at pre-inclusion and monitored under outpatient conditions
Documented HIV-1 infection regardless of clinical stage and CD4 lymphocyte count
Patient with treatment failure after first-line antiretroviral treatment with a combination including a non-nucleoside reverse transcriptase inhibitor and two nucleoside reverse transcriptase inhibitors, failure being defined as 2 measurements (at 1 month interval) of plasma HIV RNA levels > 1000 copies/ml after at least 6 months of uninterrupted treatment
Adherence (> 80%) to first- line antiretroviral treatment (questionnaire) at pre inclusion
Patient agrees not to take any concomitant medication during the trial without informing the investigator
Informed consent signed no later than D-15
For women in childbearing age: negative pregnancy test at inclusion, with no plan of pregnancy in the coming 12 months and agreeing to use mechanical contraception (with or without hormonal contraception) during the study
Exclusion Criteria:
Infection with HIV-2 or HIV-1 groups O or N or HIV1+2
Deficiency of the patient, making it difficult, if not impossible, for him/her to take part in the trial or understand the information provided to him/her
Participation in any other clinical trial
Presence of an uncontrolled, ongoing opportunistic infection or of any severe or progressive disease
First-line treatment with a protease inhibitor, abacavir, tenofovir or ddI
Ongoing treatment with rifampicin
Severe hepatic insufficiency (TP < 50%)
ALAT > 3 x ULN
Creatinine clearance calculated by Cockcroft formula < 50 ml/min
Hb ≤ 8 g/dl
Platelets < 50,000 cells/mm3
Neutrophiles < 500 cells/ mm3
Use of drugs prohibited in the context of this trial (drugs contraindicated by the SCP of the trial drugs) - in the event of tuberculosis or malaria during the trial, a list of authorized medicines and, if necessary, a dose adjustment of the antiretroviral medication will be provided
Pregnancy or lactation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sinata Koulla Shiro, PhD
Organizational Affiliation
Infectious diseases department, Central Hospital, Yaounde, Cameroon
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Papa Salif Sow, PhD
Organizational Affiliation
Infectious Diseases Department, Fann Hospital, Dakar, Senegal
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Adrien Sawadogo, MD
Organizational Affiliation
Day Hospital, CHU Sanou Souro, Bobo Dioulasso, Burkina Faso
Official's Role
Principal Investigator
Facility Information:
Facility Name
Day Hospital, CHU Sanou Souro
City
Bobo Dioulasso
Country
Burkina Faso
Facility Name
Day Hospital, Central Hospital
City
Yaounde
Country
Cameroon
Facility Name
Clinical Research and Training Center, Fann Hospital
City
Dakar
Country
Senegal
12. IPD Sharing Statement
Citations:
PubMed Identifier
31273686
Citation
Boyer S, Nishimwe ML, Sagaon-Teyssier L, March L, Koulla-Shiro S, Bousmah MQ, Toby R, Mpoudi-Etame MP, Ngom Gueye NF, Sawadogo A, Kouanfack C, Ciaffi L, Spire B, Delaporte E; 2-Lady Group. Cost-Effectiveness of Three Alternative Boosted Protease Inhibitor-Based Second-Line Regimens in HIV-Infected Patients in West and Central Africa. Pharmacoecon Open. 2020 Mar;4(1):45-60. doi: 10.1007/s41669-019-0157-9.
Results Reference
derived
Learn more about this trial
Evaluation of Three Strategies of Second-line Antiretroviral Treatment in Africa (Dakar - Bobo-Dioulasso - Yaoundé)
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