Clinical trial NCT01192035: PI or NNRTI as First-line Treatment of HIV in West Africa - the PIONA Trial
Official title: PI or NNRTI as First-line Treatment of HIV in a West African Population With Low Adherence - the PIONA Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV-1
Keywords: Africa, Western
Antiretroviral Therapy, Highly Active
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital Skejby
name: Bandim Health Project
name: Ministry of Health, Guinea-Bissau
name: Abbott
First posted: 2010-08-31
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Fraction of patients with viral load suppression <400 copies/ml
timeFrame: 12 months after enrolment
Secondary outcomes:
measure: Fraction of patients with viral load suppression <50 copies/ml
timeFrame: 12 months after enrolment
measure: Increment of CD4+ cell count of at least 100 cells/µL
timeFrame: 12 months after enrolment
measure: Development of ≥1 resistance mutations involving the treatment regimens used in patients with viral load >400 copies/ml
timeFrame: 12 months after enrolment
measure: Frequency of adverse events and severe adverse events
timeFrame: Within 12 months
measure: Compliance.
timeFrame: Within 12 months
measure: Incidence of tuberculosis.
timeFrame: Within 12 months
measure: Death.
timeFrame: Within 12 months
measure: Weight
timeFrame: Within 12 months
measure: Plasma cytokine levels
timeFrame: Within 12 months
Other outcomes:
Locations:
city: Bissau
country: Guinea-Bissau
facility: Centro de Tratamento Ambulatoria do Hospital Nacional Simão Mendes
Study officials:
affiliation: Aarhus University Hospital Skejby
name: Sanne Jespersen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aarhus University Hospital Skejby
name: Alex L Laursen, MD, DMSc
role: STUDY_DIRECTOR
affiliation: Aarhus University Hospital Skejby
name: Lars Oestergaard, Prof MD DMSc
role: STUDY_DIRECTOR
affiliation: Aarhus University Hospital Skejby
name: Christian Wejse, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.