Drug-drug Interaction (DDI) Study of GSK3640254 With Darunavir/Ritonavir (DRV/RTV) and Etravirine (ETR)

This is an open-label, single-sequence, multiple-dose, 3 cohort study to investigate the effects of DRV/RTV and/or ETR on the pharmacokinetics (PK) of GSK3640254 and the effects of GSK3640254 on the PK of DRV/RTV and/or ETR. This study will aid in understanding these interactions and resulting changes in exposure (if any) when given in combination with GSK3640254.


Eligibility Criteria:
Inclusion criteria:

* Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
* Participants who are overtly healthy as determined by investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and screening ECG).
* Body weight more than or equal to (\>=)50.0 kilograms (kg) (110 pounds \[lbs\]) for men and \>=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 31.0 kilograms per square meter (kg/m\^2) (inclusive).
* Male or female participants:

  1. Male participants should not engage in intercourse while confined in the study site. There is no need for an extended period of double barrier use or prolonged abstinence after study discharge.
  2. Female participants:

  (i) A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a non-hormonal contraceptive method that is highly effective, with a failure rate of less than (\<)1 percent (%) for 28 days before intervention, during the intervention period, and for at least 28 days after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.

(ii) A WOCBP must have a negative highly sensitive serum or urine pregnancy test at screening and check-in (Day -1).

* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed consent form (ICF) and in this protocol.

Exclusion criteria:

* Participants with current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* A pre-existing condition interfering with normal Gastrointestinal (GI) anatomy or motility (for example \[e.g.\], gastroesophageal reflux disease, gastric ulcers, gastritis) or hepatic and/or renal function that could interfere with the absorption, metabolism, and/or excretion of the study intervention or render the participant unable to take oral study intervention.
* Prior cholecystectomy surgery (prior appendectomy is acceptable).
* Clinically significant illness, including viral syndromes within 3 weeks of dosing.
* A participant with known or suspected active Coronavirus Disease-2019 (COVID-19) infection or contact with an individual with known COVID-19, within 14 days of study enrollment (World Health Organization \[WHO\] definitions).
* Any history of significant underlying psychiatric disorder, including, but not limited to, schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder.
* Any history of major depressive disorder with or without suicidal features, or anxiety disorders that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (more than \[\>\]6 months) outpatient treatment. Participants with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy (\<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the ViiV Healthcare/GlaxoSmithKline (VH/GSK) medical monitor.
* Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the participant's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the participant.
* Medical history of cardiac arrhythmias, prior myocardial infarction in the past 3 months, or cardiac disease or a family or personal history of long QT syndrome.
* Presence of hepatitis B surface antigen at screening or within 3 months prior to starting study intervention.
* Positive hepatitis C antibody test result at screening or within 3 months prior to starting study intervention.
* Positive Human immunodeficiency virus (HIV)-1 and -2 antigen/antibody immunoassay at screening.
* Alanine aminotransferase (ALT) \>1.5 times upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
* Bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). A single repeat of any laboratory abnormality is allowed within a single screening period to determine eligibility.
* Any acute laboratory abnormality at screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
* Any Grade 2 to 4 laboratory abnormality at screening, with the exception of creatine phosphokinase (CPK), lipid abnormalities (e.g., total cholesterol, triglycerides), and ALT (described above), will exclude a participant from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any laboratory abnormality is allowed within a single screening period to determine eligibility.
* Urine drug screen positive (showing presence of): amphetamines, barbiturates, cannabinoids, cocaine, or phencyclidine, or non-prescribed opiates, oxycodone, benzodiazepines, methadone, Methylenedioxymethamphetamine (MDMA), methamphetamines, or tricyclic antidepressants at screening or before the first dose of study intervention.
* Unable to refrain from the use of prescription or nonprescription drugs including vitamins, herbal and dietary supplements (including Saint \[St\] John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study intervention and for the duration of the study.
* Treatment with any vaccine within 30 days prior to receiving study intervention.
* Unwillingness to abstain from excessive consumption of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos or their fruit juices within 7 days prior to the first dose of study intervention(s) until the end of the study.
* Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) prior to the first dosing day in the current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the study intervention (whichever is longer).
* Prior exposure to GSK3640254 or prior intolerance to DRV/RTV or ETR in this or another clinical study.
* Prior intolerance to any other study medications: DRV/RTV or ETR.
* Where participation in the study would result in donation of blood or blood products in excess of 500 milliliters (mL) within 56 days.
* Any positive (abnormal) response confirmed by the investigator on a screening clinician- or qualified designee-administered Columbia-Suicide Severity Rating Scale (C-SSRS).
* Systolic blood pressure \<100 millimeters of mercury (mm Hg). Up to 2 repeats are allowed for confirmation.
* Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the past 3 months, symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, non-sustained or sustained ventricular tachycardia, any degree of atrioventricular block, or conduction abnormality) which, in the opinion of the investigator or VH/GSK medical monitor, will interfere with the safety for the individual participant.
* Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination):

  1. Heart rate: \<50 or \>100 beats per minute (bpm).
  2. PR interval \>200 milliseconds (ms).
  3. Corrected QT interval (QTc) \>450 ms.
* History of regular alcohol consumption within 6 months of the study, defined as an average weekly intake of \>14 units. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits.
* Unable to refrain from tobacco or nicotine-containing products within 3 months prior to screening.
* History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.