- ICH GCP
- US-Register für klinische Studien
- Klinische Studie 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.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 4
Kontakte und Standorte
Studienorte
-
-
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Bissau, Guinea-Bissau
- Centro de Tratamento Ambulatoria do Hospital Nacional Simão Mendes
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Aktiver Komparator: 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.
Andere Namen:
|
Aktiver Komparator: Protease inhibitor
|
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).
Andere Namen:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
Fraction of patients with viral load suppression <400 copies/ml
Zeitfenster: 12 months after enrolment
|
12 months after enrolment
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Fraction of patients with viral load suppression <50 copies/ml
Zeitfenster: 12 months after enrolment
|
12 months after enrolment
|
|
Increment of CD4+ cell count of at least 100 cells/µL
Zeitfenster: 12 months after enrolment
|
12 months after enrolment
|
|
Development of ≥1 resistance mutations involving the treatment regimens used in patients with viral load >400 copies/ml
Zeitfenster: 12 months after enrolment
|
12 months after enrolment
|
|
Frequency of adverse events and severe adverse events
Zeitfenster: Within 12 months
|
Within 12 months
|
|
Compliance.
Zeitfenster: Within 12 months
|
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.
|
Within 12 months
|
Incidence of tuberculosis.
Zeitfenster: Within 12 months
|
Within 12 months
|
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Death.
Zeitfenster: Within 12 months
|
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.
|
Within 12 months
|
Weight
Zeitfenster: Within 12 months
|
Increase in body mass index (BMI) and frequency of severe weight loss (>10% of presumed or measured body weight).
|
Within 12 months
|
Plasma cytokine levels
Zeitfenster: Within 12 months
|
Within 12 months
|
Mitarbeiter und Ermittler
Sponsor
Mitarbeiter
Ermittler
- Hauptermittler: Sanne Jespersen, MD, Aarhus University Hospital Skejby
- Studienleiter: Alex L Laursen, MD, DMSc, Aarhus University Hospital Skejby
- Studienleiter: Lars Oestergaard, Prof MD DMSc, Aarhus University Hospital Skejby
- Studienstuhl: Christian Wejse, MD, PhD, Aarhus University Hospital Skejby
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antiinfektiva
- Antivirale Mittel
- Reverse-Transkriptase-Inhibitoren
- Inhibitoren der Nukleinsäuresynthese
- Enzym-Inhibitoren
- Anti-HIV-Agenten
- Antiretrovirale Mittel
- Protease-Inhibitoren
- Cytochrom P-450 CYP3A-Inhibitoren
- Cytochrom-P-450-Enzym-Inhibitoren
- Cytochrom P-450-Enzyminduktoren
- Cytochrom P-450 CYP3A-Induktoren
- HIV-Protease-Inhibitoren
- Virale Protease-Inhibitoren
- Cytochrom P-450 CYP2B6-Induktoren
- Cytochrom P-450 CYP2C9-Inhibitoren
- Cytochrom P-450 CYP2C19-Inhibitoren
- Nevirapin
- Ritonavir
- Lopinavir
- Efavirenz
Andere Studien-ID-Nummern
- 11/CNES/2010
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
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