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- Ensayo clínico NCT01192035
PI or NNRTI as First-line Treatment of HIV in West Africa - the PIONA Trial (PIONA)
PI or NNRTI as First-line Treatment of HIV in a West African Population With Low Adherence - the PIONA Trial
BACKGROUND: Since 1996 the combination of three or more drugs has been the mainstay of human immunodeficiency virus (HIV) treatment. The most important types of drugs are called nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleotide reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) Response to treatment is measured as increasing CD4+ cell count and decreasing HIV viral load. A major problem is the development of resistance. NNRTIs are recommended as part of first-line treatment of HIV in Africa but many Africans have a slower NNRTI clearance than Caucasians making them more susceptible for development of resistance in case of treatment interruptions. PIs might therefore be a better option in an African setting with low adherence.
AIM: To evaluate two different treatment regimens in HIV-1 infected patients:
A) A NNRTI (efavirenz/nevirapine) based regimen and B) A PI (ritonavir-boosted lopinavir) based regimen with regard to treatment outcomes. HYPOTHESIS: Treatment with a PI will be superior to treatment with a NNRTI due to less development of resistance.
METHODS: Treatment-naïve adult HIV-1 patients enrolled in an existing cohort The West African Retrovirus and Acquired Immune Deficiency (WARAID) cohort in Guinea Bissau with CD4+ cell count ≤ 350 cells/µL and/or clinical signs of immune suppression (World Health Organization (WHO) clinical stage 3 or 4) will be randomised 1:1 to: Treatment A: 2 NRTIs (lamivudine and either zidovudine or stavudine) and 1 NNRTI (efavirenz or nevirapine) or Treatment B: 2 NRTIs (same as in treatment A) and 1 PI (ritonavir-boosted lopinavir). Primary outcome: Viral load suppression <400 copies/ml 12 months after enrolment.
PERSPECTIVES: Guidelines for treatment of HIV in Africa are more or less a copy of the guidelines used in Europe and North America. Genetic differences in pharmacokinetics, more women infected in Africa and difficulties ensuring good adherence mean that results obtained from Caucasian patients are not directly transferrable to African patients. The results of this study will hopefully help guiding the treatment of HIV in Africa in the future. The investigators believe the HIV infected people in West Africa deserve the same evidence-based medicine as in developed countries.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 4
Contactos y Ubicaciones
Ubicaciones de estudio
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-
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Bissau, Guinea-Bisáu
- Centro de Tratamento Ambulatoria do Hospital Nacional Simão Mendes
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Antiretroviral treatment (ART) naïve HIV-1 infected patients. Women receiving ART during pregnancy can be included.
- Age ≥ 18 years
- CD4+ cell count ≤ 350 cells/µL and/or
- Clinical signs of immune suppression (WHO clinical stage 3 or 4) irrespective of CD4+ cell count.
Exclusion Criteria:
- Tuberculosis (TB) treatment with rifampicin at the time of enrolment.
- Co-infection with HIV-2.
- Grade 3 or 4 alanine transaminase (ALAT) elevation (>5 times upper normal limit).
- Patients with cerebral disturbances that complicates the ability to give informed consent or follow the treatment regime.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Comparador activo: NNRTI
|
2 NRTIs (lamivudine 150 mg "bis in die - twice a day" (BID) and either zidovudine 300 mg BID if hemoglobin is ≥ 8 g/L or stavudine 30 mg BID if hemoglobin is < 8 g/L) and 1 NNRTI (efavirenz 600 mg "omne in die - once daily" (OD) or nevirapine 200 mg OD for the first 2 weeks and after that 200 mg BID).
Efavirenz will be used in all male patients according to national HIV guidelines.
Pregnant patients and female patients with a child bearing potential will be treated with nevirapine if CD4+ cell count is ≤ 350 cells/mm3 with close monitoring of liver enzymes during the first 12 weeks in patients with CD4+ cell count >250 cells/mm3.
Females beyond childbearing age will be treated with efavirenz.
Otros nombres:
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Comparador activo: Protease inhibitor
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2 NRTIs (lamivudine 150 mg BID and either zidovudine 300 mg BID if hemoglobin is ≥ 8 g/L or stavudine 30 mg BID if hemoglobin is < 8 g/L) and 1 PI (ritonavir-boosted lopinavir 400/100 mg BID).
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
---|---|
Fraction of patients with viral load suppression <400 copies/ml
Periodo de tiempo: 12 months after enrolment
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12 months after enrolment
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Fraction of patients with viral load suppression <50 copies/ml
Periodo de tiempo: 12 months after enrolment
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12 months after enrolment
|
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Increment of CD4+ cell count of at least 100 cells/µL
Periodo de tiempo: 12 months after enrolment
|
12 months after enrolment
|
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Development of ≥1 resistance mutations involving the treatment regimens used in patients with viral load >400 copies/ml
Periodo de tiempo: 12 months after enrolment
|
12 months after enrolment
|
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Frequency of adverse events and severe adverse events
Periodo de tiempo: Within 12 months
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Within 12 months
|
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Compliance.
Periodo de tiempo: Within 12 months
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Compliance defined as the actual amount of medicine taken compared to the planned amount for the same treatment period.
A pill count is carried out at each visit.
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Within 12 months
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Incidence of tuberculosis.
Periodo de tiempo: Within 12 months
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Within 12 months
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Death.
Periodo de tiempo: Within 12 months
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Death at 12 month follow-up.
Any patient lost to follow-up will be attempted visited at home by a field assistant 1 month after latest visit due.
Information on patient death from family or neighbors will be recorded as a mortality event and a verbal autopsy conducted.
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Within 12 months
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Weight
Periodo de tiempo: Within 12 months
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Increase in body mass index (BMI) and frequency of severe weight loss (>10% of presumed or measured body weight).
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Within 12 months
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Plasma cytokine levels
Periodo de tiempo: Within 12 months
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Within 12 months
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Sanne Jespersen, MD, Aarhus University Hospital Skejby
- Director de estudio: Alex L Laursen, MD, DMSc, Aarhus University Hospital Skejby
- Director de estudio: Lars Oestergaard, Prof MD DMSc, Aarhus University Hospital Skejby
- Silla de estudio: Christian Wejse, MD, PhD, Aarhus University Hospital Skejby
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Antivirales
- Inhibidores de la transcriptasa inversa
- Inhibidores de la síntesis de ácidos nucleicos
- Inhibidores de enzimas
- Agentes Anti-VIH
- Agentes antirretrovirales
- Inhibidores de la proteasa
- Inhibidores del citocromo P-450 CYP3A
- Inhibidores de enzimas del citocromo P-450
- Inductores de enzimas de citocromo P-450
- Inductores de citocromo P-450 CYP3A
- Inhibidores de la proteasa del VIH
- Inhibidores de la proteasa viral
- Inductores de citocromo P-450 CYP2B6
- Inhibidores del citocromo P-450 CYP2C9
- Inhibidores del citocromo P-450 CYP2C19
- Nevirapina
- Ritonavir
- Lopinavir
- Efavirenz
Otros números de identificación del estudio
- 11/CNES/2010
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
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