INTELENCE (étravirine)

Key points

Favourable opinion for reimbursement in the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced children 2 to 6 years of age.

What therapeutic improvement?

Therapeutic improvement in management.

Role in the care pathway?

In the event of virologic failure, treatment should preferably combine a ritonavir-boosted protease inhibitor (active P/r, primarily darunavir/r; in exceptional cases tipranavir/r), combination of two PIs is not recommended, combined with another two active antiretrovirals from among:

• etravirine (which frequently remains active, even in the event of resistance to efavirenz and/or nevirapine, whereas there is cross-resistance with rilpivirine);
• raltegravir (particularly in combination with darunavir/r and etravirine);
• dolutegravir, which generally remains active, at a dosage of 50 mg x2/d, in the event of resistance mutations to raltegravir or elvitegravir. The dolutegravir plus etravirine combination should not be used, except in combination with a PI/r to compensate for the enzyme inducing effect of etravirine on the metabolism of dolutegravir;
• maraviroc, if absence of virus using the CXCR4 coreceptor;
• enfuvirtide (but for which long-term use is limited by its injection form);
• one or more NRTIs. In the event of multiresistance to NRTIs (≥ 3 TAM + M184V), a residual activity of abacavir and tenofovir may persist. However, maintenance of NRTIs in the event of multiresistance to this class of antiretrovirals is not justified when fewer than three fully active antiretrovirals are available.

Role of the medicinal product in the care pathway

INTELENCE (etravirine) is an NNRTI that is frequently active on viruses resistant to the first NNRTIs (efavirenz and/or nevirapine). In accordance with its MA, INTELENCE (etravirine) is not recommended in antiretroviral treatment-naive patients.

In combination with a boosted protease inhibitor and other antiretrovirals, it is a therapeutic option for the treatment of HIV-1 infection in children of 2 to 6 years of age, as it is in previously treated adults, adolescents and children of 6 to < 18 years of age. These patients must have a detectable viral load under current antiretroviral therapy and have viral strains with resistance mutations to non-nucleoside reverse transcriptase inhibitors and protease inhibitors. Since cross-resistance with other NNRTIs is possible, genotype analysis of the reverse transcriptase should be performed prior to its prescription to verify the absence of 3 or more mutations reducing viral sensitivity to this drug.

Very rare cases of severe skin eruption, including toxic epidermal necrolysis and DRESS or severe hypersensitivity (rash, eosinophilia, which may be combined with, to varying degrees, adenopathy, hepatitis, interstitial nephritis, interstitial lung disease) have been reported within a period of 3 to 6 weeks following the start of etravirine therapy, reinforcing the need for monitoring precautions at treatment initiation. Prescribers should be informed that the incidence of skin rash was higher in female subjects (see SPC).