Overview

This trial is active, not recruiting.

Condition hiv-1
Treatments efavirenz or nevirapine, ritonavir-boosted lopinavir
Phase phase 4
Sponsor University of Aarhus
Collaborator Aarhus University Hospital Skejby
Start date May 2011
End date April 2014
Trial size 400 participants
Trial identifier NCT01192035, 11/CNES/2010

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
efavirenz or nevirapine Stocrin
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.
(Active Comparator)
ritonavir-boosted lopinavir Kaletra
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).

Primary Outcomes

Measure
Fraction of patients with viral load suppression <400 copies/ml
time frame: 12 months after enrolment

Secondary Outcomes

Measure
Fraction of patients with viral load suppression <50 copies/ml
time frame: 12 months after enrolment
Increment of CD4+ cell count of at least 100 cells/µL
time frame: 12 months after enrolment
Development of ≥1 resistance mutations involving the treatment regimens used in patients with viral load >400 copies/ml
time frame: 12 months after enrolment
Frequency of adverse events and severe adverse events
time frame: Within 12 months
Compliance.
time frame: Within 12 months
Incidence of tuberculosis.
time frame: Within 12 months
Death.
time frame: Within 12 months
Weight
time frame: Within 12 months
Plasma cytokine levels
time frame: Within 12 months

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

Official title PI or NNRTI as First-line Treatment of HIV in a West African Population With Low Adherence - the PIONA Trial
Principal investigator Sanne Jespersen, MD
Trial information was received from ClinicalTrials.gov and was last updated in December 2013.
Information provided to ClinicalTrials.gov by University of Aarhus.