A Multicentre Trial of Second-line Antiretroviral Treatment Strategies in African Adults Using Atazanavir or Lopinavir/Ritonavir

Study Overview
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Brief Summary
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In the well recognized context of HIV infection chronicity, it is now crucial to identify and evaluate effective, well tolerated and affordable second line regimen in resources limited countries where patients often change treatment after a long period of viral replication while on first line regimen. This multicentre international, randomized, non-blinded phase III trial aim to demonstrate the non-inferiority of a generic lamivudine-tenofovir-atazanavir/ritonavir regimen (daily intake) as compared to a standard emtricitabine-tenofovir-lopinavir/ritonavir (twice daily intake)regimen for second line HIV-1 treatment. by stratifying on the viral load level (between 1000 and 5000 copies/mL versus > 5000 copies/mL) at inclusion, this trial will also allow to evaluate the optimum moment for instituting the second-line treatment.

Official Title
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A Multicenter Phase III Trial of Second-line Antiretroviral Treatment Strategies in African Adults (Tanzania Ans South Africa) Using Atazanavir or Lopinavir/Ritonavir

Conditions
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HIV

Intervention / Treatment
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* Drug: Lopinavir
* Drug: Atazanavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18 and above out patient documented HIV-1 infection first line treatment failure: after first-line antiretroviral treatment with a combination including a non-nucleoside reverse transcriptase inhibitor and two nucleoside reverse transcriptase inhibitors two measurements of plasma HIV RNA levels > 1000 copies/mL after at least 6 months of uninterrupted treatment or without any major modification satisfactory compliance (>80%) to 1st line antiretroviral treatment signed informed consent agreement for contraception for women of childbearing age Exclusion Criteria: HIV-2 infection or HIV-1/HIV-2 coinfection uncontrolled, ongoing opportunistic infection or of any severe or progressive disease including active TB first line antiretroviral treatment with a protease inhibitor or tenofovir ongoing treatment with rifampicin severe hepatic insufficiency (PT < 50%) ALT < 3 times the upper limit of normal creatinine clearance calculated by Cockcroft's formula < 50 mL/min Hb <=8 g/dL; platelets < 50,000 cells/mm3; neutrophils < 500 cells/mm3 pregnancy and lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A : Lopinavir<br>Emtricitabine/tenofovir : TDF300mg.FTC200mg (Fixed Dose Combination) 1 tablet per day Lopinavir/ritonavir : LPV200mg/RTV50mg 2 tablets twice a day | Drug: Lopinavir<br>* Evaluation of second line antiretroviral regimen including boosted lopinavir<br>|
| Experimental: Arm B : Atazanavir<br>Lamivudine/tenofovir : 3TC300mg/TDF300mg (Fixed Dose Combination) 1 tablet per day Atazanavir/ritonavir : ATV300mg/RTV100mg 2 tablets once a day | Drug: Atazanavir<br>* Evaluation of second line antiretroviral regimen including boosted atazanavir<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological response | Proportion of patients with plasma HIV RNA < 50 copies/mL | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological response | Proportion of patients with plasma HIV RNA < 400 copies/mL | 12 and 24 weeks | 
| Viral resistance | Incidence of resistance mutations after treatment failure (HIV RNA < 1000 copies/mL) | 12, 24 and 48 weeks | 
| Clinical course of HIV infection | Mortality, occurence of clinical events stage 3 or 4 (WHO classification), immune reconstitution sundrome, non-AIDS clinical events including bacterial infections | Up to 48 weeks | 
| Tolerance assessment | Proportion of adverse events related to antiretroviral treatment, proportion of treatement discontinuations due to antiretroviral side effect, variation of biological parameters and metabolic markers between second line antiretroviral initiation and 24/48 weeks. | 24 and 48 weeks | 
| Adherence assessment | Measurement of pills consumption at each visit, face-to-face questionnaire with the pharmacist | At each protocol visit : week 2, 4, 12, 24, 36 and 48 | 
| Hepatitis B evaluation | Prevalence of HBs AG, HBe Ag, HBV viremia, and HBV asociated drug resistance mutations at baseline | At entry | 
| Immunologic response | Variation of circulating total and CD4+ lymphocyte count between second line treatment initiation and 24 weeks/48 weeks | 24 and 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Second line antiretroviral treatment, Sub saharian Africa, Generic