PI or NNRTI as First-line Treatment of HIV in West Africa - the PIONA Trial

NCT01192035 | Completed Phase 4 DMC

• 1 other identifier: 11/CNES/2010
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV-1

Keywords

Africa, Western; Antiretroviral Therapy, Highly Active

Outcome Measures

Primary Outcomes (1)

• Fraction of patients with viral load suppression <400 copies/ml

  12 months after enrolment

Secondary Outcomes (9)

• Fraction of patients with viral load suppression <50 copies/ml

  12 months after enrolment

• Increment of CD4+ cell count of at least 100 cells/µL

  12 months after enrolment

• Development of ≥1 resistance mutations involving the treatment regimens used in patients with viral load >400 copies/ml

  12 months after enrolment

• Frequency of adverse events and severe adverse events

  Within 12 months

• Compliance.

  Within 12 months

Study Arms (2)

NNRTI

ACTIVE COMPARATOR

Drug: Efavirenz or Nevirapine

Protease inhibitor

ACTIVE COMPARATOR

Drug: Ritonavir-boosted lopinavir

Interventions

Efavirenz or Nevirapine DRUG

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.

Also known as: Stocrin, Sustiva, Viramune

NNRTI

Ritonavir-boosted lopinavir DRUG

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).

Also known as: Kaletra, Aluvia

Protease inhibitor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital Skejby: collaborator
• Bandim Health Project: collaborator
• Ministry of Health, Guinea-Bissau: collaborator
• Abbott: collaborator

Study Sites (1)

Centro de Tratamento Ambulatoria do Hospital Nacional Simão Mendes

Bissau, Guinea-Bissau

Location

Related Publications (1)

• Jespersen S, Honge BL, Krarup H, Medstrand P, Sorensen A, Medina C, Te DDS, Correira FG, Erikstrup C, Ostergaard L, Wejse C, Laursen AL; Bissau HIV Cohort study group. Protease Inhibitors or NNRTIs as First-Line HIV-1 Treatment in West Africa (PIONA): A Randomized Controlled Trial. J Acquir Immune Defic Syndr. 2018 Nov 1;79(3):386-393. doi: 10.1097/QAI.0000000000001820.

  PMID: 30044302 DERIVED

MeSH Terms

Interventions

efavirenz; Nevirapine; lopinavir-ritonavir drug combination

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Sanne Jespersen, MD

  Aarhus University Hospital Skejby

  PRINCIPAL INVESTIGATOR

• Alex L Laursen, MD, DMSc

  Aarhus University Hospital Skejby

  STUDY DIRECTOR

• Lars Oestergaard, Prof MD DMSc

  Aarhus University Hospital Skejby

  STUDY DIRECTOR

• Christian Wejse, MD, PhD

  Aarhus University Hospital Skejby

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2010
• First Posted: August 31, 2010
• Study Start: May 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: June 25, 2015

Record last verified: 2014-11

Locations

GU (1)