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

Phase 4

Completed

Conditions: HIV-1

Interventions: Drug: Efavirenz or Nevirapine
Drug: Ritonavir-boosted lopinavir

Registration Number: NCT01192035

Lead Sponsor: University of Aarhus

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 400

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NNRTI	Efavirenz or Nevirapine	-
Protease inhibitor	Ritonavir-boosted lopinavir	-

Primary Outcome Measures

Name	Time	Method
Fraction of patients with viral load suppression <400 copies/ml	12 months after enrolment

Secondary Outcome Measures

Name	Time	Method
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
Compliance.	Within 12 months	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.
Frequency of adverse events and severe adverse events	Within 12 months
Weight	Within 12 months	Increase in body mass index (BMI) and frequency of severe weight loss (\>10% of presumed or measured body weight).
Plasma cytokine levels	Within 12 months
Death.	Within 12 months	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.
Incidence of tuberculosis.	Within 12 months