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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Aarhus University Hospital Skejby
Bandim Health Project
Ministry of Health, Guinea-Bissau
Abbott
Information provided by (Responsible Party):
University of Aarhus
ClinicalTrials.gov Identifier:
NCT01192035
First received: August 9, 2010
Last updated: December 30, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
HIV-1
Drug: Efavirenz or Nevirapine
Drug: Ritonavir-boosted lopinavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PI or NNRTI as First-line Treatment of HIV in a West African Population With Low Adherence - the PIONA Trial

Resource links provided by NLM:


Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • Fraction of patients with viral load suppression <400 copies/ml [ Time Frame: 12 months after enrolment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Fraction of patients with viral load suppression <50 copies/ml [ Time Frame: 12 months after enrolment ] [ Designated as safety issue: No ]
  • Increment of CD4+ cell count of at least 100 cells/µL [ Time Frame: 12 months after enrolment ] [ Designated as safety issue: No ]
  • Development of ≥1 resistance mutations involving the treatment regimens used in patients with viral load >400 copies/ml [ Time Frame: 12 months after enrolment ] [ Designated as safety issue: No ]
  • Frequency of adverse events and severe adverse events [ Time Frame: Within 12 months ] [ Designated as safety issue: Yes ]
  • Compliance. [ Time Frame: Within 12 months ] [ Designated as safety issue: No ]
    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.

  • Incidence of tuberculosis. [ Time Frame: Within 12 months ] [ Designated as safety issue: No ]
  • Death. [ Time Frame: Within 12 months ] [ Designated as safety issue: Yes ]
    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.

  • Weight [ Time Frame: Within 12 months ] [ Designated as safety issue: No ]
    Increase in body mass index (BMI) and frequency of severe weight loss (>10% of presumed or measured body weight).

  • Plasma cytokine levels [ Time Frame: Within 12 months ] [ Designated as safety issue: No ]

Enrollment: 400
Study Start Date: May 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: NNRTI Drug: 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.
Other Names:
  • Stocrin
  • Sustiva
  • Viramune
Active Comparator: Protease inhibitor 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).
Other Names:
  • Kaletra
  • Aluvia

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01192035

Locations
Guinea-Bissau
Centro de Tratamento Ambulatoria do Hospital Nacional Simão Mendes
Bissau, Guinea-Bissau
Sponsors and Collaborators
University of Aarhus
Aarhus University Hospital Skejby
Bandim Health Project
Ministry of Health, Guinea-Bissau
Abbott
Investigators
Principal Investigator: Sanne Jespersen, MD Aarhus University Hospital Skejby
Study Director: Alex L Laursen, MD, DMSc Aarhus University Hospital Skejby
Study Director: Lars Oestergaard, Prof MD DMSc Aarhus University Hospital Skejby
Study Chair: Christian Wejse, MD, PhD Aarhus University Hospital Skejby
  More Information

No publications provided

Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT01192035     History of Changes
Other Study ID Numbers: 11/CNES/2010
Study First Received: August 9, 2010
Last Updated: December 30, 2013
Health Authority: Guinea-Bissau: Ministry of Health

Keywords provided by University of Aarhus:
Africa, Western
Antiretroviral Therapy, Highly Active

Additional relevant MeSH terms:
Nevirapine
Efavirenz
Ritonavir
Lopinavir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on September 11, 2014