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

Phase 3

Completed

Conditions: HIV
HIV Infections

Interventions: 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)

Registration Number: NCT00928187

Lead Sponsor: ANRS, Emerging Infectious Diseases

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 454

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)	emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
Arm B	abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)	abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
Arm C	emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)	emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)

Primary Outcome Measures

Name	Time	Method
Number of Patients With Plasma HIV RNA < 50 Copies/mL	48 weeks

Secondary Outcome Measures

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

Trial Locations

Locations (3): Day Hospital, CHU Sanou Souro
🇧🇫
Bobo Dioulasso, Burkina Faso
Day Hospital, Central Hospital
🇨🇲
Yaounde, Cameroon
Clinical Research and Training Center, Fann Hospital
🇸🇳
Dakar, Senegal