Dolutegravir (formerly known as S/GSK 572) is an investigational integrase inhibitor that is in the late stages of development. It is administered once daily and does not require pharmacokinetic boosting. Two recently presented Phase 3 studies evaluated dolutegravir in combination with nucleoside/nucleotide analogues in treatment-naive subjects.
Elvitegravir is a once-daily integrase inhibitor that requires PK boosting with either ritonavir or cobicistat. It recently received FDA approval for initial therapy as part of a fixed-dose combination that includes cobicistat, tenofovir, and emtricitabine (Stribild).
Boceprevir and telaprevir, the hepatitis C virus (HCV) serine protease inhibitors, are likely to play important roles in the treatment of individuals with HIV/HCV coinfection, as well as in persons with HCV monoinfection. However, both boceprevir and telaprevir are inhibitors and substrates of cytochrome P450 3A4 (CYP3A4); thus, interactions with antiretroviral (ARV) medications used for treatment of HIV are expected, particularly HIV protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). Few studies have examined drug-drug interactions between HCV protease inhibitors and ARVs, but the available data do make it clear that the HCV PIs have significant interactions with certain ARVs. Interactions, especially those involving HIV PIs and NNRTIs, may substantially affect the efficacy or toxicity of either HCV therapy or HIV therapy (though in many cases the clinical impact of these interactions has not been studied). The table below presents a summary of known interactions between ARVs and HCV PIs, along with recommendations for coadministration.
It has been reported previously that efavirenz reduces serum levels of rilpivirine and that this effect may be prolonged, even after discontinuation of efavirenz (see Sustained Effect of Efavirenz on Rilpivirine Serum Concentrations). A small, nonrandomized study was designed to answer the question of whether it is possible to switch directly from efavirenz to rilpivirine without loss of virologic control.
Rilpivirine and Boceprevir
Boceprevir (BOC) is a hepatitis C virus (HCV) NS3/4A protease inhibitor used in combination with pegylated interferon + ribavirin for the treatment of HCV. As BOC is an inhibitor of hepatic cytochrome (CYP) 3A4, and many protease inhibitors and NNRTIs affect or are affected by this hepatic isoenzyme, interactions are expected.
Cobicistat is a derivative of ritonavir and a potent inhibitor of CYP3A. As does ritonavir, it "boosts" blood levels of other substrates of this enzyme but, unlike ritonavir, it has no activity against HIV. It has been developed as a pharmacokinetic enhancer of the integrase inhibitor elvitegravir and of some PIs.
Tenofovir alafenamide fumarate (TAF) is an investigational prodrug of tenofovir. You will recall that the current tenofovir product, tenofovir disoproxil fumarate (TDF), also is a prodrug; so why are we interested in a new prodrug? This largely has to do with efforts to decrease the toxicity associated with tenofovir.
It has been demonstrated previously that ritonavir significantly increases serum levels of inhaled and intranasal fluticasone and that coadministration with fluticasone should be avoided. Few studies have examined interactions between PIs and other corticosteroids. At the 19th Conference on Retroviruses and Opportunistic Infections, researchers presented results from a randomized controlled PK study of interactions of both darunavir/ritonavir and ritonavir (alone) with inhaled beclomethasone.