With only about one-quarter of Americans living with HIV being virally suppressed, more Americans becoming newly infected each year, and an aging cohort of HIV specialty care providers (who started providing care to HIV infected persons in the 1980’s), it is essential that health professional training programs incorporate curricula and experience regarding HIV prevention, diagnosis, care, and treatment.
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.
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.
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.
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.
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.
In early 2011, a single-arm study of the NRTI-sparing regimen of darunavir/ritonavir (800/100 mg QD) plus raltegravir (400 mg BID) reported worrisome rates of virologic failure, particularly among subjects with baseline HIV RNA levels of >100,000 copies/mL.(1) At ICAAC, researchers involved in a second study to evaluate this combination presented their 24-week results.
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.