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

• ClinicalTrials.gov Identifier: NCT00928187
• Recruitment Status: Completed
• First Posted: June 25, 2009
• Results First Posted: November 8, 2016
• Last Update Posted: February 27, 2017
• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: Gilead Sciences; Janssen Pharmaceutica
• Information provided by (Responsible Party): ANRS, Emerging Infectious Diseases

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.

Condition or disease	Intervention/treatment	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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 454 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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)
• Study Start Date: November 2009
• Actual Primary Completion Date: September 2013
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm A; emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)	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 (WHO recommended second line)	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 (Second line strategy under evaluation)	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

Outcome Measures

Primary Outcome Measures :

1. Number of Patients With Plasma HIV RNA < 50 Copies/mL [ Time Frame: 48 weeks ]

Secondary Outcome Measures :

1. Number of Patients With WHO Stage 3 and 4 HIV Related Events [ Time Frame: between baseline and 48 weeks ]
   patients having a diagnosis of HIV related event classified as stage 3 or 4
2. Patients With Plasma HIV RNA < 200 Copies/ml [ Time Frame: 48 weeks ]
   number of patients with plasma HIV RNA below 200 copies/ml
3. Gain in CD4 Cells Between Baseline and W48 [ Time Frame: between baseline and 48 weeks ]
   median gain in circulating CD4 cells between baseline and W48
4. Number of Patients Discontinuing Study Treatment [ Time Frame: between baseline and W48 ]
   number of patients discounting treatment because of adverse events
5. Tolerance: Gastrointestinal Complains [ Time Frame: between baseline and 48 weeks ]
   Gastrointestinal complaints (grade 1 to 4) between baseline and W48.
6. Tolerance: Neuropathies (Grade 1 to 4) [ Time Frame: between baseline and W48 ]
   any symptom of peripheral neuropathy
7. Tolerance: Equal or Superior to a 25% Reduction in eGFR (Glomerular Filtration Rate) [ Time Frame: between baseline and W48 ]
   evaluation of estimated glomerular filtration rate and number of participant with a decrease equal or superior to 25% of the baseline value
8. Adherence [ Time Frame: between baseline and W48 ]
   number of patients in different categories of adherence as measured by questionnaire
9. Number of Patients With Resistance Mutations [ Time Frame: between W12 and W48 ]
   number of patients with resistance mutations after second line treatment failure (HIV RNA> 1000 copies/ml)
10. Development of Metabolic Syndrome [ Time Frame: from baseline to week 48 ]
    number of patients developing metabolic syndrome over a period of 48 weeks
11. Number of Patients With HIV Plasma Viral Load < 50 Copies/ml [ Time Frame: Week 24 ]
    Snapshot of patients with HIV viral load less then 50 copies/ml at week 24
12. Number of Patients With HIV Plasma Viral Load < 200 Copies/ml [ Time Frame: Week 24 ]
    number of patients having a plasma viral load below 200 copies/ml at week 24

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

Burkina Faso

Day Hospital, CHU Sanou Souro

Bobo Dioulasso, Burkina Faso

Cameroon

Day Hospital, Central Hospital

Yaounde, Cameroon

Senegal

Clinical Research and Training Center, Fann Hospital

Dakar, Senegal

Sponsors and Collaborators

ANRS, Emerging Infectious Diseases

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: ANRS, Emerging Infectious Diseases
• ClinicalTrials.gov Identifier: NCT00928187
• Other Study ID Numbers: ANRS12169 2LADY
• First Posted: June 25, 2009
• Results First Posted: November 8, 2016
• Last Update Posted: February 27, 2017
• Last Verified: January 2017

Keywords provided by ANRS, Emerging Infectious Diseases:

HIV; Second line treatment; WHO recommendations; Africa; Treatment strategies; treatment experienced

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Ritonavir; Lopinavir; Darunavir; Tenofovir; Emtricitabine; Abacavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Didanosine; HIV Protease Inhibitors; Viral Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP3A Inhibitors