HIV
Conditions
Keywords
HIV, Second line antiretroviral treatment, Sub saharian Africa, Generic
Brief summary
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.
Interventions
DRUGLopinavir
Evaluation of second line antiretroviral regimen including boosted lopinavir
DRUGAtazanavir
Evaluation of second line antiretroviral regimen including boosted atazanavir
Sponsors
European and Developing Countries Clinical Trials Partnership (EDCTP)
Ludwig-Maximilians - University of Munich
Institute of Tropical Medicine, Belgium
Institut de Recherche pour le Developpement
Swiss National Science Foundation
University of Limpopo
NIMR-Mbeya Medical Research Program (MMRP)/ Mbeya Referral Hospital, Tanzania
ANRS, Emerging Infectious Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Virological response | 48 weeks | Proportion of patients with plasma HIV RNA \< 50 copies/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Viral resistance | 12, 24 and 48 weeks | Incidence of resistance mutations after treatment failure (HIV RNA \< 1000 copies/mL) |
| Clinical course of HIV infection | Up to 48 weeks | Mortality, occurence of clinical events stage 3 or 4 (WHO classification), immune reconstitution sundrome, non-AIDS clinical events including bacterial infections |
| Tolerance assessment | 24 and 48 weeks | 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. |
| Virological response | 12 and 24 weeks | Proportion of patients with plasma HIV RNA \< 400 copies/mL |
| Hepatitis B evaluation | At entry | Prevalence of HBs AG, HBe Ag, HBV viremia, and HBV asociated drug resistance mutations at baseline |
| Immunologic response | 24 and 48 weeks | Variation of circulating total and CD4+ lymphocyte count between second line treatment initiation and 24 weeks/48 weeks |
| Adherence assessment | At each protocol visit : week 2, 4, 12, 24, 36 and 48 | Measurement of pills consumption at each visit, face-to-face questionnaire with the pharmacist |
Countries
South Africa, Tanzania
Outcome results
None listed