Evaluation of Three Strategies of Second-line Antiretroviral Treatment in Africa (Dakar - Bobo-Dioulasso - Yaoundé)
Condition: HIV; HIV Infections
MeSH terms: HIV Infections
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)
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; 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 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
Intervention MeSH terms: Ritonavir; Lopinavir; Darunavir; Tenofovir; Emtricitabine; Abacavir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Didanosine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 454.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; Second line treatment; WHO recommendations; Africa; Treatment strategies; treatment experienced

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.
    

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