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

NCT00928187 | Completed Phase 3 Results DMC

• 1 other identifier: ANRS12169 2LADY
• Study Type: interventional
• Target: 454
• Locations: 3 countries
• Sites: 3

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.

Conditions

HIV; HIV Infections

Keywords

HIV; Second line treatment; WHO recommendations; Africa; Treatment strategies; treatment experienced

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Plasma HIV RNA < 50 Copies/mL

  48 weeks

Secondary Outcomes (12)

• Number of Patients With WHO Stage 3 and 4 HIV Related Events

  between baseline and 48 weeks

• Patients With Plasma HIV RNA < 200 Copies/ml

  48 weeks

• Gain in CD4 Cells Between Baseline and W48

  between baseline and 48 weeks

• Number of Patients Discontinuing Study Treatment

  between baseline and W48

• Tolerance: Gastrointestinal Complains

  between baseline and 48 weeks

Study Arms (3)

Arm A

ACTIVE COMPARATOR

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

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

Arm B

ACTIVE COMPARATOR

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

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

Arm C

ACTIVE COMPARATOR

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

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

Interventions

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

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

Arm A

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

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

Arm B

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

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

Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patient agrees not to take any concomitant medication during the trial without informing the investigator
• Informed consent signed no later than D-15

You may not qualify if:

• 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

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• Gilead Sciences: collaborator
• Janssen Pharmaceutica: collaborator

Study Sites (3)

Day Hospital, CHU Sanou Souro

Bobo-Dioulasso, Burkina Faso

Location

Day Hospital, Central Hospital

Yaoundé, Cameroon

Location

Clinical Research and Training Center, Fann Hospital

Dakar, Senegal

Location

Related Publications (1)

• 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.

  PMID: 31273686 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Emtricitabine; Tenofovir; Lopinavir; abacavir; Didanosine; Ritonavir; Darunavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrimidinones; Inosine; Purine Nucleosides; Dideoxynucleosides; Ribonucleosides; Thiazoles; Sulfur Compounds; Azoles; Sulfonamides; Amides; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Furans

Limitations and Caveats

Limitations: open label design, random imbalance at baseline. Non-inferiority not shown, results influenced by the hypothesis of 80% viral success (50 copies/mL), not reached (69% in the control group). Therefore, the study power was reduced (80%).

Results Point of Contact

• Title: Dr Laura Ciaffi
• Organization: UMI 233 IRD Montpellier

lauraciaffi2002@yahoo.fr

00237 694926786

Study Officials

• Sinata Koulla Shiro, PhD

  Infectious diseases department, Central Hospital, Yaounde, Cameroon

  PRINCIPAL INVESTIGATOR

• Papa Salif Sow, PhD

  Infectious Diseases Department, Fann Hospital, Dakar, Senegal

  PRINCIPAL INVESTIGATOR

• Adrien Sawadogo, MD

  Day Hospital, CHU Sanou Souro, Bobo Dioulasso, Burkina Faso

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2009
• First Posted: June 25, 2009
• Study Start: November 1, 2009
• Primary Completion: September 1, 2013
• Study Completion: December 1, 2015
• Last Updated: February 27, 2017
• Results First Posted: November 8, 2016

Record last verified: 2017-01

Locations

SE (1); CA (1); BU (1)