Clinical trial NCT00928187: Evaluation of Three Strategies of Second-line Antiretroviral Treatment in Africa (Dakar - Bobo-Dioulasso - Yaoundé)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
HIV Infections
Keywords: HIV
Second line treatment
WHO recommendations
Africa
Treatment strategies
treatment experienced
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Gilead Sciences
name: Janssen Pharmaceutica
First posted: 2009-06-25
Enrollment: 454
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Patients With Plasma HIV RNA < 50 Copies/mL
timeFrame: 48 weeks
Secondary outcomes:
measure: Number of Patients With WHO Stage 3 and 4 HIV Related Events
timeFrame: between baseline and 48 weeks
measure: Patients With Plasma HIV RNA < 200 Copies/ml
timeFrame: 48 weeks
measure: Gain in CD4 Cells Between Baseline and W48
timeFrame: between baseline and 48 weeks
measure: Number of Patients Discontinuing Study Treatment
timeFrame: between baseline and W48
measure: Tolerance: Gastrointestinal Complains
timeFrame: between baseline and 48 weeks
measure: Tolerance: Neuropathies (Grade 1 to 4)
timeFrame: between baseline and W48
measure: Tolerance: Equal or Superior to a 25% Reduction in eGFR (Glomerular Filtration Rate)
timeFrame: between baseline and W48
measure: Adherence
timeFrame: between baseline and W48
measure: Number of Patients With Resistance Mutations
timeFrame: between W12 and W48
measure: Development of Metabolic Syndrome
timeFrame: from baseline to week 48
measure: Number of Patients With HIV Plasma Viral Load < 50 Copies/ml
timeFrame: Week 24
measure: Number of Patients With HIV Plasma Viral Load < 200 Copies/ml
timeFrame: Week 24
Other outcomes:
Locations:
city: Bobo Dioulasso
country: Burkina Faso
facility: Day Hospital, CHU Sanou Souro
city: Yaounde
country: Cameroon
facility: Day Hospital, Central Hospital
city: Dakar
country: Senegal
facility: Clinical Research and Training Center, Fann Hospital
Study officials:
affiliation: Infectious diseases department, Central Hospital, Yaounde, Cameroon
name: Sinata Koulla Shiro, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Infectious Diseases Department, Fann Hospital, Dakar, Senegal
name: Papa Salif Sow, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Day Hospital, CHU Sanou Souro, Bobo Dioulasso, Burkina Faso
name: Adrien Sawadogo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.