Study of Novel Antiretrovirals in Participants With HIV-1

Phase 1

Completed

• Conditions: HIV-1-infection
• Interventions: Drug: B/F/TAF; Drug: Bavtavirine; Drug: bavtavirine; Drug: GS-1720; Drug: GS-6212; Drug: Standard of Care (Substudy 01); Drug: Standard of Care (Substudy 02); Drug: Standard of Care (Substudy 03)

• Registration Number: NCT05585307
• Lead Sponsor: Gilead Sciences

Brief Summary

Master protocol: The goal of this master clinical trial study is to learn how novel antiretrovirals (medicines that stop the virus from multiplying) affect the human immunodeficiency virus-1 (HIV-1) infection in people living with HIV (PWH).

Substudy-01 (GS-US-544-5905-01) will evaluate bavtavirine in PWH.

Substudy-02 (GS-US-544-5905-02) will evaluate GS-1720 in PWH.

Substudy-03 (GS-US-544-5905-03) will evaluate GS-6212 in PWH.

Detailed Description

This umbrella study will begin with a substudy of bavtavirine (Substudy-01), and later substudies GS-1720 (Substudy-02) and GS-6212 (Substudy-03) will be added. Substudies evaluating additional study drugs will be added in a staggered manner when relevant nonclinical and/or clinical data become available.

* Substudy-01 enrollment closed, actual enrollment is 13.

* Substudy-02 enrollment closed, actual enrollment is 28.

* Substudy-03 enrollment closed, actual enrollment is 8.

Study Timeline

• Study First Submitted: 2022-10-14
• Study First Submitted QC: 2022-10-14
• Study First Posted: 2022-10-18
• Study Start: 2022-10-26
• Primary Completion: 2024-02-17
• Study Completion: 2024-03-18
• Results First Submitted: 2025-03-07
• Status Verified: 2025-04
• Results First Submitted QC: 2025-04-18
• Last Update Submitted: 2025-04-18
• Results First Posted: 2025-05-08
• Last Update Posted: 2025-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

All Substudies:

• Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) ≥ 5000 copies/mL but ≤ 400,000 copies/mL at screening.
• Cluster of differentiation 4 (CD4) cell count > 200 cells/mm^3 at screening.
• Antiretroviral (ARV) treatment-naive or treatment-experienced but naive to the investigational ARV drug class being investigated in the given substudy and have not received any ARV within 12 weeks of screening, including medications received for pre-exposure prophylaxis (PrEP) or postexposure prophylaxis (PEP) (note that current or prior receipt of long acting (LA) parenteral ARVs such as monoclonal antibodies (mAbs) targeting HIV-1, injectable cabotegravir (CAB), or injectable rilpivirine (RPV) is exclusionary).
• Have adequate renal function (estimated glomerular filtration rate (eGFR) ≥ 70 mL/min/1.73 m^2)
• No clinically significant abnormalities in electrocardiogram (ECG) at screening.

Substudy-01, Substudy-02, and Substudy-03:

• Participants in substudy-01 should be willing to initiate a non-NNRTI based SOC ART on Day 11.
• Participants in substudy-02 and Substudy-03 should be willing to initiate any SOC ART on Day 11.
• Willing and able to comply with meal requirements on dosing days.

Key

Exclusion Criteria

All Substudies:

• Known historical genotypic or phenotypic resistance to 4 major ARV classes (nucleoside reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI), integrase strand-transfer inhibitor (INSTI)).

• History of an AIDS-defining condition including present at the time of screening.

• Active, serious infections (other than HIV-1) requiring therapy and including active tuberculosis infection < 30 days prior to randomization.

• History of or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).

• Any other serious or active clinical condition or prior therapy that, in the opinion of the investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements.

• Hepatitis C virus (HCV) antibody positive and detectable HCV RNA.

• Chronic hepatitis B virus (HBV) infection, as determined by either:

  • Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit, or
  • Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit.

• Hepatic transaminases (aspartate aminotransferase (AST) or alanine aminotransferase (ALT)) > 5 x upper limit of normal (ULN).

• Current alcohol or substance use judged by the investigator to potentially interfere with individual study compliance.

• Positive serum pregnancy test at screening or a positive pregnancy test prior to Day 1.

• Individuals with plan to breastfeed during the study period including the protocol-defined follow-up period.

• Requirement for ongoing therapy with or prior use of any prohibited medications listed in the protocol. Any prescription medications or over the counter medications, including herbal products, within 28 days prior to start of study drug dosing must be reviewed and approved by the sponsor, with the exception of vitamins and/or acetaminophen and/or ibuprofen.

• Any current or prior receipt of LA parenteral ARVs such as mAbs targeting HIV-1, injectable CAB, or injectable RPV, for treatment or prophylaxis (PrEP, PEP).

Substudy-01, Substudy-02, Substudy-03:

• Requirement for ongoing therapy with any prohibited medications listed in protocol.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Substudy-02: GS-1720	B/F/TAF	Participants will receive GS-1720. After assessments on Day 11 or upon ET, participants will initiate a regimen of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY)), or an alternative SOC ART regimen up to Day 60. SOC ART regimen, example INSTIs: DTG/ABC/3TC or DTG/3TC Approximately 5 cohorts may enroll. Participants will be enrolled in Cohort 1 initially and then dosing in subsequent cohorts will proceed after safety review team (SRT) review of emerging data.
Substudy-02: GS-1720	GS-1720	Participants will receive GS-1720. After assessments on Day 11 or upon ET, participants will initiate a regimen of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY)), or an alternative SOC ART regimen up to Day 60. SOC ART regimen, example INSTIs: DTG/ABC/3TC or DTG/3TC Approximately 5 cohorts may enroll. Participants will be enrolled in Cohort 1 initially and then dosing in subsequent cohorts will proceed after safety review team (SRT) review of emerging data.
Substudy-01: Bavtavirine	B/F/TAF	Participants will receive bavtavirine. After assessments on Day 11 or upon early termination (ET), participants will initiate a regimen of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY)), or other non-nonnucleoside reverse transcriptase inhibitor (NNRTI) based standard of care (SOC) antiretroviral therapy (ART) regimen up to Day 39. Non-NNRTI SOC ART regimen may include: * abacavir (ABC)/dolutegravir (DTG)/lamivudine (3TC), (ABC/DTG/3TC) * DTG plus (tenofovir alafenamide fumarate (TAF) or tenofovir disoproxil fumarate (TDF) plus (emtricitabine (FTC) or 3TC) Approximately 5 cohorts may enroll. Participants will be enrolled in Cohort 1 initially and then dosing in subsequent cohorts will proceed after safety review team (SRT) review of emerging data.
Substudy-01: Bavtavirine	Standard of Care (Substudy 01)	Participants will receive bavtavirine. After assessments on Day 11 or upon early termination (ET), participants will initiate a regimen of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY)), or other non-nonnucleoside reverse transcriptase inhibitor (NNRTI) based standard of care (SOC) antiretroviral therapy (ART) regimen up to Day 39. Non-NNRTI SOC ART regimen may include: * abacavir (ABC)/dolutegravir (DTG)/lamivudine (3TC), (ABC/DTG/3TC) * DTG plus (tenofovir alafenamide fumarate (TAF) or tenofovir disoproxil fumarate (TDF) plus (emtricitabine (FTC) or 3TC) Approximately 5 cohorts may enroll. Participants will be enrolled in Cohort 1 initially and then dosing in subsequent cohorts will proceed after safety review team (SRT) review of emerging data.
Substudy-02: GS-1720	Standard of Care (Substudy 02)	Participants will receive GS-1720. After assessments on Day 11 or upon ET, participants will initiate a regimen of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY)), or an alternative SOC ART regimen up to Day 60. SOC ART regimen, example INSTIs: DTG/ABC/3TC or DTG/3TC Approximately 5 cohorts may enroll. Participants will be enrolled in Cohort 1 initially and then dosing in subsequent cohorts will proceed after safety review team (SRT) review of emerging data.
Substudy-03: GS-6212	B/F/TAF	Participants will receive GS-6212. After assessment on Day 11 or upon ET, participants will initiate a regimen of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY)), or an alternative SOC ART regimen up to Day 25. Approximately 5 cohorts may enroll. Participants will be enrolled in Cohort 1 initially and then dosing in subsequent cohorts will proceed after safety review team (SRT) review of emerging data.
Substudy-03: GS-6212	Standard of Care (Substudy 03)	Participants will receive GS-6212. After assessment on Day 11 or upon ET, participants will initiate a regimen of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY)), or an alternative SOC ART regimen up to Day 25. Approximately 5 cohorts may enroll. Participants will be enrolled in Cohort 1 initially and then dosing in subsequent cohorts will proceed after safety review team (SRT) review of emerging data.
Substudy 01: Cohort 1: Bavtavirine 675 mg (High-Fat Meal)	Bavtavirine	Participants receive a single dose of bavtavirine 675 mg tablet with a high-fat meal on Day 1. After assessments on Day 11 or upon early termination (ET), the participants initiate a regimen of B/F/TAF, or an alternative standard of care (SOC) antiretroviral (ART) regimen (example INSTI + NRTIs: dolutegravir (DTG)/abacavir (ABC)/3TC or DTG/3TC) up to Day 39.
Substudy 01: Cohort 1: Bavtavirine 675 mg (High-Fat Meal)	B/F/TAF	Participants receive a single dose of bavtavirine 675 mg tablet with a high-fat meal on Day 1. After assessments on Day 11 or upon early termination (ET), the participants initiate a regimen of B/F/TAF, or an alternative standard of care (SOC) antiretroviral (ART) regimen (example INSTI + NRTIs: dolutegravir (DTG)/abacavir (ABC)/3TC or DTG/3TC) up to Day 39.
Substudy 01: Cohort 1: Bavtavirine 675 mg (High-Fat Meal)	Standard of Care (Substudy 01)	Participants receive a single dose of bavtavirine 675 mg tablet with a high-fat meal on Day 1. After assessments on Day 11 or upon early termination (ET), the participants initiate a regimen of B/F/TAF, or an alternative standard of care (SOC) antiretroviral (ART) regimen (example INSTI + NRTIs: dolutegravir (DTG)/abacavir (ABC)/3TC or DTG/3TC) up to Day 39.
Substudy 01: Cohort 2: Bavtavirine 1200 mg (Low-Fat Meal)	Bavtavirine	Participants receive a single dose of bavtavirine 1200 mg tablet with a low-fat meal on Day 1. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.
Substudy 01: Cohort 2: Bavtavirine 1200 mg (Low-Fat Meal)	B/F/TAF	Participants receive a single dose of bavtavirine 1200 mg tablet with a low-fat meal on Day 1. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.
Substudy 01: Cohort 2: Bavtavirine 1200 mg (Low-Fat Meal)	Standard of Care (Substudy 01)	Participants receive a single dose of bavtavirine 1200 mg tablet with a low-fat meal on Day 1. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.
Substudy 01: Cohort 3: Bavtavirine 900 mg (High-Fat Meal)	B/F/TAF	Participants receive bavtavirine 900 mg tablet with a high-fat meal on Days 1 and 2. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.
Substudy 01: Cohort 3: Bavtavirine 900 mg (High-Fat Meal)	Bavtavirine	Participants receive bavtavirine 900 mg tablet with a high-fat meal on Days 1 and 2. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.
Substudy 01: Cohort 3: Bavtavirine 900 mg (High-Fat Meal)	Standard of Care (Substudy 01)	Participants receive bavtavirine 900 mg tablet with a high-fat meal on Days 1 and 2. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 39.
Substudy 02: Cohort 1: GS-1720 450 mg	B/F/TAF	Participants receive a single dose of GS-1720 450 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Substudy 02: Cohort 1: GS-1720 450 mg	GS-1720	Participants receive a single dose of GS-1720 450 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Substudy 02: Cohort 1: GS-1720 450 mg	Standard of Care (Substudy 02)	Participants receive a single dose of GS-1720 450 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Substudy 02: Cohort 2: GS-1720 150 mg	B/F/TAF	Participants receive a single dose of GS-1720 150 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Substudy 02: Cohort 2: GS-1720 150 mg	GS-1720	Participants receive a single dose of GS-1720 150 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Substudy 02: Cohort 2: GS-1720 150 mg	Standard of Care (Substudy 02)	Participants receive a single dose of GS-1720 150 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Substudy 02: Cohort 3: GS-1720 30 mg	B/F/TAF	Participants receive a single dose of GS-1720 30 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Substudy 02: Cohort 3: GS-1720 30 mg	GS-1720	Participants receive a single dose of GS-1720 30 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Substudy 02: Cohort 3: GS-1720 30 mg	Standard of Care (Substudy 02)	Participants receive a single dose of GS-1720 30 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Substudy 02: Cohort 4: GS-1720 900 mg	B/F/TAF	Participants receive a single dose of GS-1720 900 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Substudy 02: Cohort 4: GS-1720 900 mg	GS-1720	Participants receive a single dose of GS-1720 900 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Substudy 02: Cohort 4: GS-1720 900 mg	Standard of Care (Substudy 02)	Participants receive a single dose of GS-1720 900 mg tablet on both Days 1 and 2 in fasted condition. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 60.
Substudy 03: Cohort 1: GS- 6212 100 mg	B/F/TAF	Participants receive GS-6212 100 mg tablet twice daily on Days 1 through 10. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 25.
Substudy 03: Cohort 1: GS- 6212 100 mg	GS-6212	Participants receive GS-6212 100 mg tablet twice daily on Days 1 through 10. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 25.
Substudy 03: Cohort 1: GS- 6212 100 mg	Standard of Care (Substudy 03)	Participants receive GS-6212 100 mg tablet twice daily on Days 1 through 10. After assessments on Day 11 or upon ET, the participants initiate a regimen of B/F/TAF, or an alternative SOC ART regimen (example INSTI + NRTIs: DTG/ABC/3TC or DTG/3TC) up to Day 25.
Substudy-01: Bavtavirine	bavtavirine	Participants will receive bavtavirine. After assessments on Day 11 or upon early termination (ET), participants will initiate a regimen of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY)), or other non-nonnucleoside reverse transcriptase inhibitor (NNRTI) based standard of care (SOC) antiretroviral therapy (ART) regimen up to Day 39. Non-NNRTI SOC ART regimen may include: * abacavir (ABC)/dolutegravir (DTG)/lamivudine (3TC), (ABC/DTG/3TC) * DTG plus (tenofovir alafenamide fumarate (TAF) or tenofovir disoproxil fumarate (TDF) plus (emtricitabine (FTC) or 3TC) Approximately 5 cohorts may enroll. Participants will be enrolled in Cohort 1 initially and then dosing in subsequent cohorts will proceed after safety review team (SRT) review of emerging data.
Substudy-03: GS-6212	GS-6212	Participants will receive GS-6212. After assessment on Day 11 or upon ET, participants will initiate a regimen of Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY)), or an alternative SOC ART regimen up to Day 25. Approximately 5 cohorts may enroll. Participants will be enrolled in Cohort 1 initially and then dosing in subsequent cohorts will proceed after safety review team (SRT) review of emerging data.

Primary Outcome Measures

Name	Time	Method
Substudies 01, 02 and 03: Change From Baseline in Plasma Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) (log10 Copies/mL) at Day 11 Relative to Historical Placebo Data	Baseline, Day 11

Secondary Outcome Measures

Name	Time	Method
Substudies 01, 02 and 03: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	First dose up to last dose (Substudy 01: Up to Day 39; Substudy 02: Up to Day 60; Substudy 03: Up to Day 25)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as any AEs with an onset date on or after the study drug start date.; Percentages were rounded-off.
Substudy 03: PK Parameter: Cmax of GS-6212	Days 1 and 10 (Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8 and (optional) 12 hours postdose)	Cmax was defined as the maximum observed concentration of drug.
Substudy 03: PK Parameter: AUC0-8h of GS-6212	Days 1 and 10 (Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8 and (optional) 12 hours postdose)	AUC0-8h was defined as the area under the concentration versus time curve spanning from 0 to 8 hours post dose.
Substudy 03: PK Parameter: AUCtau of GS-6212	Day 10 (Parameter estimated based on observed data from 0 to 8 hours postdose)	AUCtau was defined as the area under the curve from time zero to end of dosing interval.
Substudy 03: PK Parameter: Plasma Concentration of GS-6212	Days 1 and 10: 8 hours postdose
Substudy 03: PK Parameter: Cavg of GS-6212 (Day 10)	Day 10 (predose to 8 hours postdose)	Cavg was defined as average plasma concentration during dose administration.
Substudy 01: Maximum Inhibitory Quotient (IQ) of Bavtavirine by Mean Plasma Concentration (Ct) up to Day 11	Up to Day 11	Inhibitory quotient was calculated as the ratio of bavtavirine in vivo exposure to in vitro plasma concentration. IQ is defined as paEC95. paEC95 = protein-adjusted effective concentration to achieve 95% effective inhibition. The IQ ≥ 2 indicated higher reduction in viral load with less rebound.
Substudies 01, 02 and 03: Change From Baseline in Plasma HIV-1 RNA (log10 Copies/mL) at Day 8 Relative to Historical Placebo Data	Baseline, Day 8
Substudy 01: PK Parameter: AUC of Bavtavirine	Day 1 up to Day 11	AUC was defined as the area under the concentration versus time curve.
Substudy 01: PK Parameter: Plasma Concentration of Bavtavirine	Days 8 and 11
Substudy 02: PK Parameter: AUC of GS-1720	Day 1 up to Day 11	AUC was defined as the area under the concentration versus time curve.
Substudy 02: PK Parameter: Plasma Concentration of GS-1720	Days 8 and 11
Substudies 01, 02 and 03: Percentage of Participants With Graded Laboratory Abnormalities	First dose up to last dose (Substudy 01: Up to Day 39; Substudy 02: Up to Day 60; Substudy 03: Up to Day 25)	Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any time postbaseline. Laboratory abnormalities were graded using Division of AIDS (DAIDS) scale with grade 0 to 4 where 0 = no grade; 1 = mild, 2 = moderate, 3 = severe; 4 = potentially life-threatening. Participants with at least a 1 grade increased from baseline for an individual laboratory test where the maximum post baseline laboratory abnormality was 1) grade 1 or higher and 2) grade 3 or higher were reported. The maximum postbaseline toxicity grade across all tests for an individual participant was used in analysis. Percentages were rounded-off.
Substudy 01: Pharmacokinetic (PK) Parameter: Cmax of Bavtavirine	Cohorts 1, 2 and 3 (Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, and 12 hours postdose); Cohort 3: Day 2: Predose, 0.5, 1, 2, 3, 4, 5, 6, and 8 hours postdose	Cmax was defined as the maximum observed concentration of drug.
Substudy 03: PK Parameter: Ctrough of GS-6212 (Day 10)	Day 10 (Parameter estimated based on observed data from 0 to 8 hours postdose)	Ctrough was defined as concentration at the end of the dosing interval.
Substudies 01, 02 and 03: Percentage of Participants at Any Measurement Achieving HIV-1 RNA < 50 Copies/mL by Day 11 at Each Dose Level	Up to Day 11	Percentages were rounded-off.
Substudies 01, 02 and 03: Percentage of Participants With Emergence of Viral Resistance to the ARV Class of the Given Drug	Up to Day 11	The antiretroviral (ARV) class of given drugs would be BVY or NNRTIs (Substudy 01) or INSTIs (Substudy 02) or INSTIs (Substudy 03).; Percentages were rounded-off.
Substudy 02: Inhibitory Quotient (IQ) of GS-1720 by Mean Plasma Concentration (Ct) at Day 11	Day 11	Inhibitory quotient was calculated as the ratio of GS-1720 in vivo exposure to in vitro plasma concentration. IQ is defined as paEC95. paEC95 = protein-adjusted effective concentration to achieve 95% effective inhibition. The IQ ≥ 2 indicated higher reduction in viral load with less rebound.
Substudy 03: Inhibitory Quotient (IQ) of GS-6212 by Ctrough at Day 11	Day 11	Ctrough is the plasma concentration of the drug just before the next dose. Inhibitory quotient was calculated as the ratio of GS-1720 in vivo exposure to in vitro Ctrough. IQ is defined as paEC95. paEC95 = protein-adjusted effective concentration to achieve 95% effective inhibition. The IQ ≥ 2 indicated higher reduction in viral load with less rebound.
Substudy 02: PK Parameter: Cmax of GS-1720	Days 1 and 2: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8 and (optional) 12 hours postdose	Cmax was defined as the maximum observed concentration of drug.

Trial Locations

Locations (42)

Washington Health Institute,Substudy-02; 🇺🇸 Washington, District of Columbia, United States

Washington Health Institute,Substudy-01; 🇺🇸 Washington, District of Columbia, United States

Washington Health Institute,Substudy-03; 🇺🇸 Washington, District of Columbia, United States

Midland Florida Clinical Research Center, LLC,Substudy-02; 🇺🇸 DeLand, Florida, United States

Midland Florida Clinical Research, LLC,Substudy-03; 🇺🇸 DeLand, Florida, United States

Midway Immunology and Research Center,Substudy-01; 🇺🇸 Fort Pierce, Florida, United States

Midway Immunology and Research Center,Substudy-03; 🇺🇸 Fort Pierce, Florida, United States

Bliss Health,Substudy-02; 🇺🇸 Orlando, Florida, United States

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT),Substudy-02; 🇹🇭 Bangkok, Thailand

Faculty of Medicine, Srinagarind Hospital, Khon Kaen University,Substudy-03; 🇹🇭 Khon Kaen, Thailand

Long Beach Education and Research Consultants,Substudy-03; 🇺🇸 Long Beach, California, United States

Central Texas Clinical Research,Substudy-01; 🇺🇸 Austin, Texas, United States

Central Texas Clinical Research,Substudy-03; 🇺🇸 Austin, Texas, United States

Mills Clinical Research,Substudy-02; 🇺🇸 Los Angeles, California, United States

Mills Clinical Research,Substudy-03; 🇺🇸 Los Angeles, California, United States

Quest Clinical Research,Substudy-02; 🇺🇸 San Francisco, California, United States

Quest Clinical Research,Substudy-03; 🇺🇸 San Francisco, California, United States

Quest Clinical Research,Substudy-01; 🇺🇸 San Francisco, California, United States

Triple O Research Institute, P.A.,Substudy-01; 🇺🇸 West Palm Beach, Florida, United States

Triple O Research Institute, P.A.,Substudy-03; 🇺🇸 West Palm Beach, Florida, United States

Infectious Disease Specialists of Atlanta,Substudy-01; 🇺🇸 Decatur, Georgia, United States

Indiana CTSI Clinical Research Center,Substudy-01; 🇺🇸 Indianapolis, Indiana, United States

University of Cincinnati College of Medicine,Substudy-02; 🇺🇸 Cincinnati, Ohio, United States

University of Cincinnati College of Medicine,Substudy-03; 🇺🇸 Cincinnati, Ohio, United States

Prism Health North Texas,Substudy-02; 🇺🇸 Dallas, Texas, United States

Prism Health North Texas,Substudy-03; 🇺🇸 Dallas, Texas, United States

North Texas Infectious Diseases Consultant, P.A.,Substudy-02; 🇺🇸 Dallas, Texas, United States

North Texas Infectious Diseases Consultants, P.A.,Substudy-03; 🇺🇸 Dallas, Texas, United States

Therapeutic Concepts, PA,Substudy-02; 🇺🇸 Houston, Texas, United States

Therapeutic Concepts, PA,Substudy-03; 🇺🇸 Houston, Texas, United States

The Crofoot Research Center, Inc.,Substudy-01; 🇺🇸 Houston, Texas, United States

AXCES Research,Substudy-02; 🇺🇸 El Paso, Texas, United States

AXES Research Group LLC,Substudy-03; 🇺🇸 El Paso, Texas, United States

MultiCare Rockwood Main Clinic- Research,Substudy-03; 🇺🇸 Spokane, Washington, United States

Yale University; School of Medicine; AIDS Program (Administrative & Study Supplies),Substudy-03; 🇺🇸 New Haven, Connecticut, United States

Orlando Immunology Center,Substudy-01; 🇺🇸 Orlando, Florida, United States

Orlando Immunology Center,Substudy-03; 🇺🇸 Orlando, Florida, United States

Instituto Dominicano de Estudio Virologicos - IDEV,Substudy-02; 🇩🇴 Santo Domingo, Dominican Republic

Bliss Health,Substudy-03; 🇺🇸 Orlando, Florida, United States

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT),Substudy-03; 🇹🇭 Bangkok, Thailand

Yale University,Substudy-02; 🇺🇸 New Haven, Connecticut, United States

Midway Immunology and Research Center,Substudy-02; 🇺🇸 Fort Pierce, Florida, United States