VH4524184 Proof-of-Concept in Treatment-Naïve Adults Livi... | NCT06214052

ID	Type	Description	Link
2023-507173-18-00	Other Identifier	EU CT Number

Status Module

Name	Class
GlaxoSmithKline	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
VH4524184 Dose 1	Experimental	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.	Drug: VH4524184 Drug: Antiretroviral therapy
VH4524184 Dose 2	Experimental	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.	Drug: VH4524184 Drug: Antiretroviral therapy
VH4524184 Dose 3	Experimental	Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.	Drug: VH4524184 Drug: Antiretroviral therapy
Placebo	Placebo Comparator	Participants received matching Placebo to the study intervention on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.

Name	Type	Description	Arm Group Labels	Other Names
VH4524184	Drug	VH4524184 was administered as tablets orally at Day 1.	VH4524184 Dose 1 VH4524184 Dose 2 VH4524184 Dose 3

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Monotherapy: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA)	Plasma samples were collected for the quantitative analysis of plasma HIV-1 RNA. The maximum change from baseline was calculated by determining the largest change from baseline value across all assessment timepoints during the monotherapy period. This is identified by subtracting the lowest post-dose visit value up to Day 10 (inclusive) from the baseline value. The baseline was defined as the most recent pre-dose assessment with a valid, non-missing value, including measurements from any unscheduled visits.	At Day 10

Secondary Outcomes

Measure	Description	Time Frame
Monotherapy and Follow-up: Number of Participants With Any Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE can be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Any AEs = occurrence of the symptom regardless of intensity grade.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participant must be 18 to 65 years of age inclusive at the time of signing the informed consent.
Participants who are overtly healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
Positive HIV antibody test
Documented HIV infection and Screening plasma HIV-1 RNA ≥ 3,000 copies/mL. A single repeat of this test is allowed within a single Screening period to determine eligibility.
Screening CD4+ T-cell count ≥200 cells/mm3
Treatment-naïve: No antiretrovirals (ARVs, in combination or monotherapy) received after the diagnosis of HIV-1 infection.
HIV Pre-exposure or post-exposure prophylaxis: No prior use of any INSTI (including cabotegravir) for HIV pre-exposure or post-exposure prophylaxis.
Body weight ≥50.0 kg (110 lbs.) for men and ≥45.0 kg (99 lbs) for women and BMI within the range 18.5-31.0 kg/m2 (inclusive - applies to males and females).
A participant of childbearing potential must have a negative serum hCG test at screening, and negative urine hCG test at Day 1, before the first dose of study intervention.
If a urine test cannot be confirmed as negative (e.g. ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease risk for inclusion of a female with an early undetected pregnancy.
Capable of giving signed informed consent
Participant must be willing and able to start standard-of-care ART as selected with the investigator on Study Day 10.

Exclusion Criteria:

Participants with primary HIV infection. Any evidence of an active CDC Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy during the study. Untreated syphilis infection [positive RPR at screen] without documentation of treatment. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; or other localized malignancies
Any pre-existing physical or mental condition which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
Any history of significant underlying psychiatric disorder, or a clinical assessment of suicidality based on the responses on the eCSSRS.
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 (>6 months) outpatient treatment.
Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome or sudden cardiac death. Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration.
Past or intended use of over-the-counter or prescription medication including herbal medications within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing. Specific medications listed in Section 6.9.1 may be allowed.
Participants who require concomitant medications known to be associated with a prolonged QTc.
Participants receiving any protocol-prohibited medication(s) and who are unwilling or unable to switch to an alternate medication).
The participant has ever received an investigational HIV vaccine (immunotherapeutic or immunomodulatory).
Exposure to an experimental drug or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of study intervention.
Participation in the study would result in donation of blood in excess of 500 mL within 56 days.
Exposure to more than four new investigational drugs or vaccines within 12 months prior to the first dosing day.
Current enrollment or past participation within the last 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research.

Diagnostic Assessments

Presence of HBsAg or HBcAb at screening
Positive Hepatitis C antibody test result at Screening
Positive Hepatitis C RNA test result at Screening.
Creatinine clearance (eGFR) of < 60 mL/min/1.73 m2 using CKD-EPI equation (2021).

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Bakersfield	California	93301	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
42283218	Derived	Rogg L, Nunez SA, Mingrone MV, Domingo P, Rolle CP, Guerri-Fernandez R, Estrada V, Lopez M, Hanan N, Ghita GL, Jeffrey JL, Underwood M, Castillo-Mancilla JR, Halliday F, Ezeadi E, Gartland M. Proof-of-Concept Phase 2a Trial of VH4524184 (VH-184), an Emerging Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile. Clin Infect Dis. 2026 Jun 12:ciag357. doi: 10.1093/cid/ciag357. Online ahead of print.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 29, 2023	Jun 12, 2025

Arm/Group Information

ID	Title	Description
BG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
BG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
BG002	VH4524184 Dose 3	Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
BG003	Placebo	Participants received matching Placebo to the study intervention on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
BG004	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Monotherapy: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA)

Plasma samples were collected for the quantitative analysis of plasma HIV-1 RNA. The maximum change from baseline was calculated by determining the largest change from baseline value across all assessment timepoints during the monotherapy period. This is identified by subtracting the lowest post-dose visit value up to Day 10 (inclusive) from the baseline value. The baseline was defined as the most recent pre-dose assessment with a valid, non-missing value, including measurements from any unscheduled visits.

Analysis was performed on Full Analysis Set (FAS), which included all randomized participants who received at least 1 full dose of study intervention.

Posted

Mean

Standard Deviation

Copies per milliliter (copies/mL)

At Day 10

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG002	VH4524184 Dose 3	Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG003	Placebo	Participants received matching Placebo to the study intervention on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.

Units	Counts
Participants	OG0006 OG0016 OG0027 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-1.17± 0.460 OG001-2.15± 0.254 OG002-2.31± 0.463 OG003

Secondary

Monotherapy and Follow-up: Number of Participants With Any Adverse Event (AE)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE can be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Any AEs = occurrence of the symptom regardless of intensity grade.

Analysis was performed on the Safety Set, which included all randomized participants who received at least one partial or full dose of the study intervention. As pre-specified in the protocol, the outcome measure data are reported for monotherapy and FU periods combined that includes all participants and all doses administered during the specified duration. Each participant is counted once across both the periods, reflecting the total number of participants affected by any adverse event.

Posted

Count of Participants

Participants

Day 1 to Day 38

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2

Secondary

Monotherapy and Follow-up: Number of Participants With AEs by Severity

The severity was assessed using The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table) Version 2.1 where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening and Grade 5 = Death.

Analysis was performed on Safety Set. As pre-specified in the protocol, the outcome measure data are reported for monotherapy and FU periods combined that includes all participants and all doses administered during the specified duration. Each participant is counted once across both the periods, reflecting the total number of participants affected by any adverse event.

Posted

Count of Participants

Participants

Day 1 to Day 38

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.

Secondary

Monotherapy: Number of Participants With AEs Leading to Study Treatment Discontinuation

Analysis was performed on Safety Set.

Posted

Count of Participants

Participants

Day 1 to Day 7

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG002	VH4524184 Dose 3	Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG003	Placebo

Secondary

Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP)

Blood samples were collected at the indicated timepoints.

Posted

Mean

Standard Deviation

International units per liter (IU/L)

At Baseline (Day 1), Day 2, Day 4, Day 7, Day 10, Day 17, Day 24, Day 31 and Day 38

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG002	VH4524184 Dose 3

Secondary

Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Bilirubin

Blood samples were collected at the indicated timepoints.

Posted

Mean

Standard Deviation

Micromoles per liter (μmol/L)

At Baseline (Day 1), Day 2, Day 4, Day 7, Day 10, Day 17, Day 24, Day 31 and Day 38

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG002	VH4524184 Dose 3

Secondary

Monotherapy and Follow-up: Change From Baseline for Liver Panel Laboratory Parameter: Protein

Blood samples were collected at the indicated timepoints.

Posted

Mean

Standard Deviation

Grams per liter

At Baseline (Day 1), Day 2, Day 4, Day 7, Day 10, Day 17, Day 24, Day 31 and Day 38

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG002	VH4524184 Dose 3	Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.

Secondary

Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: ALT, AST, ALP, Bilirubin

Liver panel parameters assessed were: ALT, AST, ALP, bilirubin. The parameters were graded according to DAIDS grading table Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase is defined as an increase in grade relative to baseline grade.

Posted

Count of Participants

Participants

From Baseline (Day 1) and up to Day 38

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.

Secondary

Monotherapy and Follow-up: Number of Participants With Maximum Toxicity Grade Increase Relative to Baseline in Liver Panel Laboratory Parameters: Protein

Participants are categorized based on changes in their liver panel laboratory parameters (protein) to 'Low,' 'Normal,' or 'High,' unless there is no change in their initial category. Participants whose lab values remain unchanged (e.g., 'High' to 'High') or whose values return to normal are recorded in the 'To Normal or No Change' category. Participants may be counted in both the 'To Low' and 'To High' categories if their values fluctuate between these states. As a result, the percentages may exceed 100% due to dual categorization. Participants with a missing baseline value are assumed to have a normal baseline value.

Posted

Count of Participants

Participants

From Baseline (Day 1) and up to Day 38

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2

Secondary

Monotherapy: Maximum Observed Plasma Drug Concentration (Cmax) of VH4524184

Blood samples were collected at indicated time points for Pharmacokinetic (PK) analysis of VH4524184.

Analysis was performed on PK Set, which included All participants in the Safety analysis set who had at least 1 non-missing PK assessment. Only participants with data available at the specified timepoints were included in this analysis.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram per milliliter (ng/mL)

At Day 1 and Day 7

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG002	VH4524184 Dose 3	Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.

Secondary

Monotherapy: Time to Maximum Observed Plasma Drug Concentration (Tmax) of VH4524184

Blood samples were collected at indicated time points for PK analysis of VH4524184.

Analysis was performed on PK Set. Only participants with data available at the specified timepoints were included in this analysis.

Posted

Median

Full Range

hours

At Day 1 and Day 7

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG002	VH4524184 Dose 3	Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.

Secondary

Monotherapy: Plasma Concentration of VH4524184 at Day 10

Blood samples was collected at indicated time point for PK analysis of VH4524184.

Analysis was performed on PK Set. Only participants with data available at the specified timepoint were included in this analysis.

Posted

Mean

Standard Deviation

ng/mL

At Day 10

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG002	VH4524184 Dose 3	Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.

Secondary

Monotherapy: Correlation of VH4524184 Cmax With Maximum Plasma HIV-1 RNA Log 10 Change From Baseline Through Day 10

Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value. Change from baseline is defined as post-dose visit value minus baseline value. Statistical analysis for relationship between PK parameter (Cmax) and PD measure (change from baseline in logarithm to base 10 (log10) values for maximum plasma HIV-1 RNA) were explored using an Emax non-linear mixed-effects model. The model parameters estimated were maximum response (Emax) which is defined as the maximum change (at infinite exposure) and EC50 which defines the PK parameter value that attains 50 percent (%) of the maximal effect

Analysis was performed on PK Set. Only participants with data available at the specified duration were included in this analysis.

Posted

Mean

Standard Deviation

Log10 copies/mL

From Day 1 to Day 10

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.

Secondary

Monotherapy: Number of Participants With Treatment-emergent Genotypic Resistance

Plasma samples were collected to assess treatment emergent Genotypic Resistance.

Analysis was performed on FAS.

Posted

Count of Participants

Participants

At Baseline (Day 1) and Day 10

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG002	VH4524184 Dose 3	Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.

Secondary

Monotherapy: Number of Participants With Treatment-emergent Phenotypic Resistance

Plasma samples were collected to assess treatment emergent Phenotypic Resistance.

Analysis was performed on FAS.

Posted

Count of Participants

Participants

At Baseline (Day 1) and Day 10

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG002	VH4524184 Dose 3	Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.

Secondary

Monotherapy: Change From Baseline in Cluster of Differentiation 4 (CD4+) T-cell Counts at Day 10

Blood samples were collected for assessment of T-cells subsets (CD4+ T-cells count) by flow cytometry at Day 10 compared to Baseline.

Analysis was performed on Safety Set. Only participants with data available at the specified timepoints were included in this analysis.

Posted

Mean

Standard Deviation

CD4+ million cells per Liter (10^6/L)

At Day 10 compared to Baseline (Day 1)

ID	Title	Description
OG000	VH4524184 Dose 1	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG001	VH4524184 Dose 2	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.
OG002	VH4524184 Dose 3	Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	VH4524184 Dose 1_Monotherapy	Participants received VH4524184 Dose 1 (low dose) on Day 1, Day 4, and Day 7.	6	6	2	6
EG001	VH4524184 Dose 2_Monotherapy	Participants received VH4524184 Dose 2 (medium dose) on Day 1, Day 4, and Day 7.	6	6	3	6
EG002	VH4524184 Dose 3_Monotherapy	Participants received VH4524184 Dose 3 (high) on Day 1, Day 4, and Day 7.	7	7	3	7
EG003	Placebo_Monotherapy	Participants received matching Placebo to the study intervention on Day 1, Day 4, and Day 7.	3	3	2	3
EG004	VH4524184 Dose 1_Follow-up	Participants received VH4524184, administered as Dose 1 (low dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label standard-of-care (SOC) antiretroviral therapy (ART), which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.	6	6	4	6
EG005	VH4524184 Dose 2_Follow-up	Participants received VH4524184, administered as Dose 2 (medium dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.	6	6	5	6
EG006	VH4524184 Dose 3_Follow-up	Participants received VH4524184, administered as Dose 3 (high dose) on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.	7	7	4	7
EG007	Placebo_Follow-up	Participants received matching Placebo to the study intervention on Day 1, Day 4, and Day 7. On Day 10, participants began open-label SOC ART, which was selected by the investigator and locally sourced. Participants were monitored weekly until Day 38.	3	3	2	3

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	v27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG0030 events0 affected3 at risk EG0040 events0 affected6 at risk EG0050 events0 affected6 at risk EG0061 events1 affected7 at risk EG0071 events1 affected3 at risk
Dyspepsia	Gastrointestinal disorders	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Nausea	Gastrointestinal disorders	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0022 events1 affected7 at risk EG003
Vomiting	Gastrointestinal disorders	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0021 events1 affected7 at risk EG003
Fatigue	General disorders	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected7 at risk EG003
Influenza like illness	General disorders	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected7 at risk EG003
Vessel puncture site haematoma	General disorders	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected7 at risk EG003
Rhinitis	Infections and infestations	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected7 at risk EG003
Upper respiratory tract infection	Infections and infestations	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Amylase increased	Investigations	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected7 at risk EG003
Blood pressure increased	Investigations	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Lipase increased	Investigations	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected7 at risk EG003
Dizziness	Nervous system disorders	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected7 at risk EG003
Headache	Nervous system disorders	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0021 events1 affected7 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	v27.0	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Pyrexia	General disorders	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Abdominal distension	Gastrointestinal disorders	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Gastroenteritis	Infections and infestations	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Acute Sinusitis	Infections and infestations	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Ear infection	Infections and infestations	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Herpes simplex	Infections and infestations	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Nasopharyngitis	Infections and infestations	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Skin infection	Infections and infestations	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Tooth abscess	Infections and infestations	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Alanine aminotransferase increased	Investigations	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Irritability	Psychiatric disorders	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Nervousness	Psychiatric disorders	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Hypertension	Vascular disorders	v27.0	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003

ID	Term
D015658	HIV Infections
D000163	Acquired Immunodeficiency Syndrome
D014777	Virus Diseases

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D015229	Sexually Transmitted Diseases, Viral
D012749	Sexually Transmitted Diseases
D016180	Lentivirus Infections
D012192	Retroviridae Infections
D012327	RNA Virus Infections
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D007153	Immunologic Deficiency Syndromes
D007154	Immune System Diseases
D012897	Slow Virus Diseases

ID	Term
D004359	Drug Therapy, Combination
D004358	Drug Therapy
D013812	Therapeutics