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Evaluation of Three Strategies of Second-line Antiretroviral Treatment in Africa (Dakar - Bobo-Dioulasso - Yaoundé) (2LADY)

This study is currently recruiting participants.
Verified October 2012 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
Collaborators:
Gilead Sciences
Janssen Pharmaceutica
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )
ClinicalTrials.gov Identifier:
NCT00928187
First received: June 23, 2009
Last updated: October 19, 2012
Last verified: October 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
HIV
HIV Infections
 Drug: emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
Drug: abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
Drug: emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • proportion of patients with plasma HIV RNA < 50 copies/mL [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • clinical outcome (AIDS events, non-AIDS events, death, undesirable effects) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • proportion of patients with plasma HIV RNA < 200 and 50 copies/ml [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • proportion of patients with plasma HIV RNA < 200 copies/ml [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • variation of circulating CD4+ lymphocyte count [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • treatment discontinuation [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
  • tolerance, particularly the occurrence of hypersensitivity syndromes, renal impairment, and changes in lipids profile, gastrointestinal complains and lipodystrophy [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
  • changes in anthropometric measures [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
  • adherence (measured by pill count and questionnaire) [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
  • frequency of resistance mutations after second line treatment failure (HIV RNA> 1000 copies/ml) [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • proportion of patient with lipodystrophia and metabolic syndrome (ANRS122250 associated study) [ Time Frame: at randomisation and at week 48 ] [ Designated as safety issue: No ]

    A sub group of 300 patients will undergo questionnaire on risk factors and following measurement:

    • anthropometric measurement
    • bone mineral density by ultrasonography
    • metabolic serological markers: glycemia, HDL, TG, Cholesterol, vitamin D, insulinemia, ...
    • inflamatory serological markers
    • vitamin


Estimated Enrollment: 450
Study Start Date: November 2009
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
emtricitabine/tenofovir + lopinavir/ritonavir
 Drug: emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
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
Active Comparator: Arm B
abacavir + didanosine + lopinavir/ritonavir
 Drug: abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
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
Active Comparator: Arm C
emtricitabine/tenofovir + darunavir + ritonavir
 Drug: emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00928187

Contacts
Contact: Eric Delaporte, PhD +33 4 67 41 62 97 eric.delaporte@ird.fr
Contact: Sinata Koulla Shiro, PhD +237 22 22 11 55 koullasinata@yahoo.fr

Locations
Burkina Faso
Day Hospital, CHU Sanou Souro Recruiting
Bobo Dioulasso, Burkina Faso
Sub-Investigator: Arserne Hema, MD            
Cameroon
Day Hospital, Central Hospital Recruiting
Yaounde, Cameroon
Sub-Investigator: Elodie Mazoyer, MD            
Senegal
Clinical Research and Training Center, Fann Hospital Recruiting
Dakar, Senegal
Sub-Investigator: Ndeye Fatou Ngom, MD            
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Gilead Sciences
Janssen Pharmaceutica
Investigators
Principal Investigator: Sinata Koulla Shiro, PhD Infectious diseases department, Central Hospital, Yaounde, Cameroon
Principal Investigator: Papa Salif Sow, PhD Infectious Diseases Department, Fann Hospital, Dakar, Senegal
Principal Investigator: Adrien Sawadogo, MD Day Hospital, CHU Sanou Souro, Bobo Dioulasso, Burkina Faso
  More Information

No publications provided

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )
ClinicalTrials.gov Identifier: NCT00928187     History of Changes
Other Study ID Numbers: ANRS12169 2LADY
Study First Received: June 23, 2009
Last Updated: October 19, 2012
Health Authority: Cameroon: Ministry of Public Health

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
HIV
Second line treatment
WHO recommendations
 Africa
Treatment strategies
treatment experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Didanosine
Tenofovir
Tenofovir disoproxil
Abacavir
 Ritonavir
Lopinavir
Darunavir
Emtricitabine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on March 07, 2013