Efficacy and pharmacokinetics of a switch from a regimen consisting of emtricitabine, nevirapine and tenofovir to rilpivirine, emtricitabine and tenofovir in virologically suppressed HIV-1 infected patients.

Rationale:

Patients treated for HIV often have to switch from one antiretroviral (ARV) to another for side effects. Nevirapine (NVP) is an
ARV used for the treatment of HIV infected patients. It is a strong
inducer of CYP3A4. Rilpivirine (RPV) is a new ARV that has shown efficacy
and excellent tolerability in 2 recent phase III clinical trials. It is
also metabolised through a CYP3A4 pathway. This study will evaluate the
impact of NVP CYP3A4 induction on the pharmacokinetics (PK) of RPV when
patients switch from NVP to RPV. Furthermore, the safety of a switch from
NVP to RPV will be evaluated.



Objective:

To evaluate the safety of a switch from NVP to RPV. To measure
the impact of NVP CYP 3A4 induction on Cmin serum levels of RPV when
patients switch therapy from NVP to RPV. For this goal RPV trough
concentrations will be compared with the mean Cmin of 80 ng/ml observed in
2 phase III trials in which RPV 25mg qd was given to treatment naïve HIV-
1 infected patients.



Study design:

This is a single arm intervention study.



Study population:

50 adult HIV-1 infected patients treated with NVP,
emtricitabine (FTC) and tenofovir (TDF) with an undetectable HIV plasma
viral load for 6 months will switch from TDF, FTC, NVP to TDF, FTC,
RPV 25mg qd. This latter treatment will be given as a single tablet
regimen (Eviplera®) that includes FTC, TDF and RPV.



Intervention: Switch from NVP to RPV.



Main study parameters/endpoints:

Primary endpoint: Number of subjects with HIV-1 RNA <50 c/mL at Week 12 (ITT
population, snapshot analysis).

Secondary endpoint: Cmin RPV levels in patients that switch from NVP to
RPV at 1, 2, 4, 6, 8, 12 and 24 weeks in comparison with Cmin observed in
fase III RPV trial. Number of subjects with HIV-1 RNA <50 c/mL at Week 24
and 48 post-switch (ITT population, snapshot analysis).

1. Switching from a nevirapine based HAART regimen to a rilpivirine based HAART regimen is save in patients with undetectable plasma HIV RNA at the time of switch;

2. Nevirapine induces the CYP3A4 mediated metabolism of rilpivirine.

12, 24, 48 for HIV RNA plasma load assessment;

1, 2, 3, 4, 8 weeks for PK assessment.

Switch from nevirapine to Eviplera® (=rilpivirine, emtricitabine, tenofovir) in patients treated with nevirapine, tenofovir and emtricitabine.