ATC Group: J05AR Antivirals for treatment of HIV infections, combinations

Darunavir is an inhibitor of the dimerisation and of the catalytic activity of the HIV-1 protease. It selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in virus infected cells, thereby preventing the formation of mature infectious virus particles. Cobicistat is a mechanism-based inhibitor of cytochromes P450 of the CYP3A subfamily. Inhibition of CYP3A-mediated metabolism by cobicistat enhances the systemic exposure of CYP3A substrates, such as darunavir, where bioavailability is limited and half-life is shortened due to CYP3A-dependent metabolism.

Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) and nucleoside analogue of 2'-deoxycytidine. Tenofovir alafenamide is a nucleotide reverse transcriptase inhibitor (NtRTI) and phosphonamidate prodrug of tenofovir (2'-deoxyadenosine monophosphate analogue). They both inhibit HIV replication through incorporation into viral DNA by the HIV RT, which results in DNA chain-termination. They have activity against HIV-1, HIV-2, and HBV.

Efavirenz is an NNRTI of HIV-1. Efavirenz non-competitively inhibits HIV-1 reverse transcriptase (RT) and does not significantly inhibit human immunodeficiency virus-2 (HIV-2) RT or cellular deoxyribonucleic acid (DNA) polymerases (α, β, γ, and δ). Emtricitabine is a nucleoside analogue of cytidine. Tenofovir disoproxil is converted in vivo to tenofovir, a nucleoside monophosphate (nucleotide) analogue of adenosine monophosphate. Emtricitabine and tenofovir are phosphorylated by cellular enzymes to form emtricitabine triphosphate and tenofovir diphosphate, respectively, which competitively inhibit HIV-1 reverse transcriptase, resulting in DNA chain termination.

Emtricitabine is a nucleoside analogue of cytidine. Tenofovir disoproxil is converted in vivo to tenofovir, a nucleoside monophosphate (nucleotide) analogue of adenosine monophosphate. Both emtricitabine and tenofovir have activity that is specific to HIV-1, HIV-2 and, HBV. Rilpivirine is a diarylpyrimidine NNRTI of HIV-1. Rilpivirine activity is mediated by non-competitive inhibition of HIV-1 reverse transcriptase (RT).

Abacavir and lamivudine are NRTIs, and are potent selective inhibitors of HIV-1 and HIV-2 (LAV2 and EHO) replication. Both abacavir and lamivudine are metabolised sequentially by intracellular kinases to the respective 5'-triphosphate (TP) which are the active moieties. Their main antiviral activity is through incorporation of the monophosphate form into the viral DNA chain, resulting in chain termination.

Lamivudine and dolutegravir combination is indicated for the treatment of Human Immunodeficiency Virus type 1 (HIV-1) infection in adults and adolescents. Dolutegravir inhibits HIV integrase and lamivudine, via its active metabolite 5'-triphosphates (TP) (an analogue for cytidine), inhibits reverse transcriptase of HIV-1 and HIV-2.

Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral Deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle. Abacavir and lamivudine are potent selective inhibitors of HIV-1 and HIV-2.

Lamivudine is a nucleoside analogue. Intracellularly, lamivudine is phosphorylated to its active 5'-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC-TP is inhibition of HIV-1 reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue. Tenofovir diphosphate inhibits the activity of HIV-1 RT by competing with the natural substrate deoxyadenosine 5'-triphosphate and, after incorporation into DNA, by DNA chain termination. Doravirine is a pyridinone non-nucleoside reverse transcriptase inhibitor of HIV-1 and inhibits HIV-1 replication by non-competitive inhibition of HIV-1 RT.

Lopinavir provides the antiviral activity of lopinavir/ritonavir. Lopinavir is an inhibitor of the HIV-1 and HIV-2 proteases. Inhibition of HIV protease prevents cleavage of the gag-pol polyprotein resulting in the production of immature, non-infectious virus.

Emtricitabine is a nucleoside analogue of cytidine. Tenofovir disoproxil is converted in vivo to tenofovir, a nucleoside monophosphate (nucleotide) analogue of adenosine monophosphate. Both emtricitabine and tenofovir have activity that is specific to human immunodeficiency virus (HIV-1 and HIV-2) and hepatitis B virus.

Lamivudine and zidovudine are nucleoside analogues which have activity against HIV. Additionally, lamivudine has activity against hepatitis B virus (HBV). Both medicinal products are metabolised intracellularly to their active moieties, lamivudine 5'-triphosphate (TP) and zidovudine 5'-TP respectively. Their main modes of action are as chain terminators of viral reverse transcription.

Abacavir, lamivudine and zidovudine are all NRTIs, and are potent selective inhibitors of HIV-1 and HIV-2.All three medicinal products are metabolised sequentially by intracellular kinases to the respective 5′-triphosphate (TP). Lamivudine-TP, carbovir-TP (the active triphosphate form of abacavir) and zidovudine-TP are substrates for and competitive inhibitors of HIV reverse transcriptase (RT). However, their main antiviral activity is through incorporation of the monophosphate form into the viral DNA chain, resulting in chain termination. Abacavir, lamivudine and zidovudine triphosphates show significantly less affinity for host cell DNA polymerases.