HIV
Conditions
Keywords
Active Comparator, Placebo Comparator, Sham Comparator, No intervention, Other, Treatment Experienced
Brief summary
This is a 48 week randomized, prospective, controlled, open-label, proof-of-concept pilot clinical trial. Patients with HIV-1 infection on HAART PI-based regimen will be randomized to switch from the PI to etravirine (400 mg dissolved in water every 24 hours) or to continue with the same approach. The aim of the study is to compare the virological efficacy of the etravirine-based regimen with standard PI-containing regimen.
Detailed description
Etravirine is a second generation non-nucleoside analogue reverse transcriptase inhibitor (NNRTI) approved by the U.S. Food and Drug Administration (FDA) in January 2008 and by the European Medicines Agency in September 2008 for clinical use in adults with incomplete virologic suppression and resistance to previous NNRTI and other antiretroviral classes. A question that has not been explored is whether subjects with sustained undetectable HIV-1 RNA-levels experiencing antiretroviral-related toxicity can safely switch their current PI to etravirine. This treatment strategy could allow improvements in tolerability and lipid profile and would permit an easy posology (400 mg dissolved in water every 24 hours). We designed a proof-of-concept study to test the efficacy and safety of switching from a Protease Inhibitor (PI) to etravirine in subjects with viral suppression as an antiretroviral strategy of simplification therapy, based on the high antiviral potency, low toxicity, together with its easy posology (in water dissolution). Patients with HIV-1 infection on HAART PI-based regimen will be randomized to switch from the PI to etravirine (400 mg dissolved in water every 24 hours) or to continue with the same approach. The primary endpoint would be the percentage of patients who maintain virological suppression at week 48.
Interventions
DRUGEtravirine 400 mg dissolved in water every 24 hours
Switch from the PI to Etravirine 400 mg dissolved in water every 24 hours
DRUGContinue with the same antiretroviral regimen
Continue with the same antiretroviral regimen
Sponsors
Germans Trias i Pujol Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Adult patient having a diagnosis of HIV-1 infection. 2. Antiretroviral therapy started at least 12 months before, always with a HAART combination including 2 NRTIs plus a PI. 3. Maintained undetectable plasma HIV-1 RNA (VL \< 50 copies/mL) since the beginning of antiretroviral therapy, for at least 6 months. 4. Absence of suspected or documented resistance mutations in the RT associated to NNRTIs or to any NRTI. 5. Patient having at least one of the following conditions: * Dyslipemia (LDL cholesterol \>130 mg/dL or triglycerides \> 350 mg/dL) derived from their current PI regimen or current use of lipid-lowering agents due to dyslipemia, * Antiretroviral-related gastrointestinal disturbances, or * Low patient's satisfaction associated with the current regimen posology (BID regimen, ritonavir use, ritonavir intolerance…). 6. Good treatment adherence. 7. Voluntary written informed consent.
Exclusion criteria
1. Previous therapy with mono or dual antiretroviral therapies after initial of HAART era. 2. Previous antiretroviral treatment failures, treatment interruptions (A) or blips (B) in viral load (VL \> 50 copies/mL). 3. Acute infections or uncontrolled chronic infection in the 2 months previous to the inclusion. 4. Pregnancy or fertile women willing to be pregnant. 5. Clinically significant malabsorption syndrome within 30 days prior to randomization. (A) Patients who in the past made any interruption of treatment (provide that it has not been in the last year) may be considered candidates for the study, if they meet other criteria for inclusion, since the break in the treatment should not assume the emergence of mutations. (B) Small blips that are preceded or forwarded by 2 undetectable viral loads will not be taken in care.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Viral load | week 48 after baseline |
Secondary
| Measure | Time frame |
|---|---|
| Genotypic test | if virologic failure occurs |
| Lipid profile: total, HDL-, LDL-cholesterol and triglyceride levels | evolution from baseline to week 48 |
| Administration of lipid-lowering drugs throughout the study | from baseline to week 48 |
| CD4+/CD8+ T lymphocytes count | evolution from baseline to week 48 |
| Patient's satisfaction assessed by 2 scales of type Likert | evolution from baseline to week 48 |
| Adverse events related to antiretroviral treatment | from baseline to week 48 |
| Etravirine plasma trough concentration | Week 4 |
| Cardiovascular risk assessed by the SCORE equation | evolution from baseline to week 48 |
Countries
Spain
Outcome results
None listed