Switching From Protease Inhibitor (PI) to Etravirine in HIV-1 Infected Subjects With Viremia Suppression

• CD4+/CD8+ T lymphocytes count [ Time Frame: evolution from baseline to week 48 ] [ Designated as safety issue: No ]
• Genotypic test [ Time Frame: if virologic failure occurs ] [ Designated as safety issue: No ]
• Lipid profile: total, HDL-, LDL-cholesterol and triglyceride levels [ Time Frame: evolution from baseline to week 48 ] [ Designated as safety issue: No ]
• Administration of lipid-lowering drugs throughout the study [ Time Frame: from baseline to week 48 ] [ Designated as safety issue: No ]
• Cardiovascular risk assessed by the SCORE equation [ Time Frame: evolution from baseline to week 48 ] [ Designated as safety issue: No ]
• Patient's satisfaction assessed by 2 scales of type Likert [ Time Frame: evolution from baseline to week 48 ] [ Designated as safety issue: No ]
• Adverse events related to antiretroviral treatment [ Time Frame: from baseline to week 48 ] [ Designated as safety issue: No ]
• Etravirine plasma trough concentration [ Time Frame: Week 4 ] [ Designated as safety issue: Yes ]

• CD4+/CD8+ T lymphocytes count [ Time Frame: Baseline, weeks 4, 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
• Genotypic test [ Time Frame: if virologic failure occurs ] [ Designated as safety issue: No ]
• Lipid profile: total, HDL-, LDL-cholesterol and triglyceride levels [ Time Frame: Baseline, weeks 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
• Administration of lipid-lowering drugs throughout the study [ Time Frame: Baseline, weeks 12, 24, 36 and 48 ] [ Designated as safety issue: No ]
• Cardiovascular risk assessed by the SCORE equation [ Time Frame: Baseline and week 48 ] [ Designated as safety issue: No ]
• Patient's satisfaction assessed by 2 scales of type Likert [ Time Frame: Baseline, weeks 24 and 48 ] [ Designated as safety issue: No ]
• Adverse events related to antiretroviral treatment [ Time Frame: Baseline, weeks 12, 24, 36 and 48 ] [ Designated as safety issue: No ]

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.

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.

• Drug: Etravirine 400 mg dissolved in water every 24 hours
  Switch from the PI to Etravirine 400 mg dissolved in water every 24 hours
  Other Name: ETV
• Drug: Continue with the same antiretroviral regimen
  Continue with the same antiretroviral regimen
  Other Name: CNT

• Experimental: Etravirine group
  To switch from the PI to Etravirine 400 mg dissolved in water every 24 hours
  Intervention: Drug: Etravirine 400 mg dissolved in water every 24 hours
• Active Comparator: Control group
  Continue with the same antiretroviral regimen
  Intervention: Drug: Continue with the same antiretroviral regimen

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.