Details of the Drug Combination

General Information of Drug Combination (ID: DCS1C4L)

• Drug Combination Name: Rilpivirine + GSK1265744
• Indication: HIV Infections; Status: Phase 3 [1]
• Component Drugs:
  Rilpivirine (DMJ0QOW): Small molecular drug
  GSK1265744 (DMT8J0I): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Rilpivirine

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[2]
Pain	MG30-MG3Z	Investigative	[3]

Rilpivirine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Inhibitor	[5]
Voltage-gated sodium channel alpha Nav1.8 (SCN10A)	TT90XZ8	SCNAA_HUMAN	Inhibitor	[3]

Rilpivirine Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[7]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[8]
UDP-glucuronosyltransferase 1A4 (UGT1A4)	DELOY3P	UD14_HUMAN	Metabolism	[7]

Indication(s) of GSK1265744

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Phase 3	[4]

GSK1265744 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Integrase (HIV IN)	TT5FH9Y	POL_HV1B1	Inhibitor	[9]

GSK1265744 Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[10]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[10]

References

• [1] ClinicalTrials.gov (NCT05917509) A Study to Evaluate the Efficacy, Safety, Participant Choice and Preference of an Oral Once-daily Regimen or a Long-acting Injectable Regimen Every Two Months for Treatment of Human Immunodeficiency Virus (HIV-1) in Adults Who Have Not Previously Taken Antiretroviral Therapy
• [2] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [3] Structures of muO-conotoxins from Conus marmoreus. I nhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian senso... J Biol Chem. 2004 Jun 11;279(24):25774-82.
• [4] ClinicalTrials.gov (NCT02951052) Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current Antiretroviral Regimen in Virologically Suppressed HIV-1-infected Adults. U.S. National Institutes of Health.
• [5] Emerging antiviral drugs. Expert Opin Emerg Drugs. 2008 Sep;13(3):393-416.
• [6] Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro. Int J Antimicrob Agents. 2013 May;41(5):484-7.
• [7] Human biotransformation of the nonnucleoside reverse transcriptase inhibitor rilpivirine and a cross-species metabolism comparison. Antimicrob Agents Chemother. 2013 Oct;57(10):5067-79.
• [8] Population pharmacokinetics and pharmacogenetics analysis of rilpivirine in HIV-1-infected individuals. Antimicrob Agents Chemother. 2016 Dec 27;61(1).
• [9] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [10] Disposition and metabolism of cabotegravir: a comparison of biotransformation and excretion between different species and routes of administration in humans. Xenobiotica. 2016;46(2):147-62.