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

NCT ID: NCT01192035

Last Updated: 2015-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2014-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NNRTI

Group Type: ACTIVE_COMPARATOR

Efavirenz or Nevirapine

Intervention Type: 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.

Protease inhibitor

Group Type: ACTIVE_COMPARATOR

Ritonavir-boosted lopinavir

Intervention Type: 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).

Interventions

Efavirenz or Nevirapine

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.

Intervention Type: DRUG

Ritonavir-boosted lopinavir

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).

Intervention Type: DRUG

Other Intervention Names

Stocrin; Sustiva; Viramune; Kaletra; Aluvia

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aarhus University Hospital Skejby

OTHER

Sponsor Role: collaborator

Bandim Health Project

OTHER

Sponsor Role: collaborator

Ministry of Health, Guinea-Bissau

UNKNOWN

Sponsor Role: collaborator

Abbott

INDUSTRY

Sponsor Role: collaborator

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sanne Jespersen, MD

Role: PRINCIPAL_INVESTIGATOR

Aarhus University Hospital Skejby

Alex L Laursen, MD, DMSc

Role: STUDY_DIRECTOR

Aarhus University Hospital Skejby

Lars Oestergaard, Prof MD DMSc

Role: STUDY_DIRECTOR

Aarhus University Hospital Skejby

Christian Wejse, MD, PhD

Role: STUDY_CHAIR

Aarhus University Hospital Skejby

Locations

Centro de Tratamento Ambulatoria do Hospital Nacional Simão Mendes

Bissau, , Guinea-Bissau

Countries

Guinea-Bissau

References

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.

Reference Type: DERIVED

PMID: 30044302 (View on PubMed)

Other Identifiers

11/CNES/2010

Identifier Type: -

Identifier Source: org_study_id