Evaluation of Three Strategies of Second-line Antiretroviral Treatment in Africa (Dakar - Bobo-Dioulasso - Yaoundé) (2LADY)
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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.
Condition | Intervention | Phase |
---|---|---|
HIV HIV Infections |
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) |
Phase 3 |
Study Type: | Interventional |
Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
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) |
- proportion of patients with plasma HIV RNA < 50 copies/mL [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- clinical outcome (AIDS events, non-AIDS events, death, undesirable effects) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
- proportion of patients with plasma HIV RNA < 200 and 50 copies/ml [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- proportion of patients with plasma HIV RNA < 200 copies/ml [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- variation of circulating CD4+ lymphocyte count [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
- treatment discontinuation [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
- tolerance, particularly the occurrence of hypersensitivity syndromes, renal impairment, and changes in lipids profile, gastrointestinal complains and lipodystrophy [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
- changes in anthropometric measures [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
- adherence (measured by pill count and questionnaire) [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: Yes ]
- frequency of resistance mutations after second line treatment failure (HIV RNA> 1000 copies/ml) [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
- proportion of patient with lipodystrophia and metabolic syndrome (ANRS122250 associated study) [ Time Frame: at randomisation and at week 48 ] [ Designated as safety issue: No ]
A sub group of 300 patients will undergo questionnaire on risk factors and following measurement:
- anthropometric measurement
- bone mineral density by ultrasonography
- metabolic serological markers: glycemia, HDL, TG, Cholesterol, vitamin D, insulinemia, ...
- inflamatory serological markers
- vitamin
Estimated Enrollment: | 450 |
Study Start Date: | November 2009 |
Estimated Study Completion Date: | September 2013 |
Estimated Primary Completion Date: | September 2013 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
Active Comparator: Arm A
emtricitabine/tenofovir + lopinavir/ritonavir
|
Drug: emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
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
|
Active Comparator: Arm B
abacavir + didanosine + lopinavir/ritonavir
|
Drug: abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
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
|
Active Comparator: Arm C
emtricitabine/tenofovir + darunavir + ritonavir
|
Drug: emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)
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
|
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Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
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
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Contact: Eric Delaporte, PhD | +33 4 67 41 62 97 | eric.delaporte@ird.fr |
Contact: Sinata Koulla Shiro, PhD | +237 22 22 11 55 | koullasinata@yahoo.fr |
Burkina Faso | |
Day Hospital, CHU Sanou Souro | Recruiting |
Bobo Dioulasso, Burkina Faso | |
Sub-Investigator: Arserne Hema, MD | |
Cameroon | |
Day Hospital, Central Hospital | Recruiting |
Yaounde, Cameroon | |
Sub-Investigator: Elodie Mazoyer, MD | |
Senegal | |
Clinical Research and Training Center, Fann Hospital | Recruiting |
Dakar, Senegal | |
Sub-Investigator: Ndeye Fatou Ngom, MD |
Principal Investigator: | 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 |
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No publications provided
Responsible Party: | French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis ) |
ClinicalTrials.gov Identifier: | NCT00928187 History of Changes |
Other Study ID Numbers: | ANRS12169 2LADY |
Study First Received: | June 23, 2009 |
Last Updated: | October 19, 2012 |
Health Authority: | Cameroon: Ministry of Public Health |
Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
HIV Second line treatment WHO recommendations |
Africa Treatment strategies treatment experienced |
Additional relevant MeSH terms:
HIV Infections Acquired Immunodeficiency Syndrome Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Didanosine Tenofovir Tenofovir disoproxil Abacavir |
Ritonavir Lopinavir Darunavir Emtricitabine Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Therapeutic Uses Anti-HIV Agents |
ClinicalTrials.gov processed this record on March 07, 2013