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

ANRS, Emerging Infectious Diseases

Status and phase: Completed; Phase 3

Conditions: HIV; HIV Infections

Treatments: Drug: emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line); Drug: emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation); Drug: abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00928187

ANRS12169 2LADY

Details and patient eligibility

About

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.

Enrollment: 454 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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454 participants in 3 patient groups

Arm A

Active Comparator group

Description:

emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)

Treatment:

Drug: emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)

Arm B

Active Comparator group

Description:

abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)

Treatment:

Drug: abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)

Arm C

Active Comparator group

Description:

emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)

Treatment:

Drug: emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)