Indications
Rilpivirine is indicated for the treatment of HIV-1 infections in antiretroviral treatment-naive patients when used in combination with other antiretroviral agents. Specifically, it is approved for individuals with HIV-1 RNA levels of ≤100,000 copies/mL and a CD4+ cell count greater than 200 cells/mm³. Moreover, the combination therapy of rilpivirine with dolutegravir is approved by the FDA for adults and adolescents aged 12 years and older, weighing·ho have their HIV-1 infection stably suppressed to less than 50 copies/mL on their current regimen for at least six months, with no history of treatment failure or resistance to either component. Rilpivirine, when combined with cabotegravir, is also approved as a complete regimen for those aged 12 years or older and weighing·heir current antiretroviral regimen, provided they are virologically suppressed with no history of treatment failure or suspected resistance to the regimen components.
Pharmacodynamics
Rilpivirine functions as a non-nucleoside reverse transcriptase inhibitor, effectively inhibiting·he replication of HIV-1. It offers a prolong·h the oral tablet administered daily and the intramuscular suspension available for monthly administration. Patients should be made aware of potential risks, including·hypersensitivity reactions, hepatotoxicity, depressive disorders, and issues related to body fat redistribution or accumulation.
Absorption
Upon administration, rilpivirine reaches its maximum concentration (Tmax) within 3-4 hours. The drug has a mean area under the curve (AUC) of 2235 ± 851 ng·h/mL. A 25 mg dose yields a peak concentration (Cmax) of 247 ng·healthy individuals and 138.6 ng·h HIV-1.
Metabolism
Rilpivirine is primarily metabolized by the cytochrome P450 enzymes CYP3A4 and CYP3A5, resulting·he formation of several hydroxylated metabolites, namely M1, M2, M3, and M4. Further metabolism involves UGT1A1 glucuronidating·he M2 metabolite to produce M6, UGT1A4 glucuronidating·he M4 metabolite to form M7.
Mechanism of Action
Rilpivirine functions as a non-competitive non-nucleoside reverse transcriptase inhibitor (NNRTI) by specifically targeting and binding to reverse transcriptase. This interaction effectively inhibits both RNA and DNA-dependent DNA polymerase activities, thus impeding HIV-1 replication. Importantly, rilpivirine does not affect human DNA polymerases α, β, and γ. Its structural flexibility, particularly around the aromatic rings, enables it to adapt to alterations in the non-nucleoside reverse transcriptase binding pocket, thereby diminishing the potential for resistance mutations in the virus.
