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

HIV Infections Clinical Trial

— 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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00928187
• Other study ID #: ANRS12169 2LADY
• Status: Active, not recruiting
• Phase: Phase 3
• First received: June 23, 2009
• Last updated: April 3, 2015
• Start date: November 2009
• Est. completion date: September 2015

Study information

• Verified date: April 2015
• 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
• Health authority: Cameroon: Ministry of Public Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 454
• Est. completion date: September 2015
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV
• HIV Infections

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Burkina Faso	Day Hospital, CHU Sanou Souro	Bobo Dioulasso
Cameroon	Day Hospital, Central Hospital	Yaounde
Senegal	Clinical Research and Training Center, Fann Hospital	Dakar

Sponsors (3)

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

Countries where clinical trial is conducted

Burkina Faso,  Cameroon,  Senegal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	proportion of patients with plasma HIV RNA < 50 copies/mL		48 weeks	No
Secondary	clinical outcome (AIDS events, non-AIDS events, death, undesirable effects)		48 weeks	Yes
Secondary	proportion of patients with plasma HIV RNA < 200 and 50 copies/ml		24 weeks	No
Secondary	proportion of patients with plasma HIV RNA < 200 copies/ml		48 weeks	No
Secondary	variation of circulating CD4+ lymphocyte count		24 and 48 weeks	No
Secondary	treatment discontinuation		24 and 48 weeks	Yes
Secondary	tolerance, particularly the occurrence of hypersensitivity syndromes, renal impairment, and changes in lipids profile, gastrointestinal complains and lipodystrophy		24 and 48 weeks	Yes
Secondary	changes in anthropometric measures		24 and 48 weeks	Yes
Secondary	adherence (measured by pill count and questionnaire)		24 and 48 weeks	Yes
Secondary	frequency of resistance mutations after second line treatment failure (HIV RNA> 1000 copies/ml)		24 and 48 weeks	No
Secondary	proportion of patient with lipodystrophia and metabolic syndrome (ANRS122250 associated study)	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, ...; inflammatory serological markers; vitamin	at randomisation and at week 48	No
Secondary	poroportin of patients with plasma HIV RNA <50 and <200 copies/ml		after 48 weeks	No