Study to Evaluate the Efficacy of GS-9131 Functional Monotherapy in Human Immunodeficiency Virus (HIV)-1-Infected Adults Failing a Nucleos(t)Ide Reverse Transcriptase Inhibitor-Containing Regimen With Nucleos(t)Ide Reverse Transcriptase Inhibitor Resistant Virus

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03472326
• Collaborator: (none)
• Enrollment: 21
• Locations: 2
• Arms: 5
• Actual Duration (Months): 20.2
• Patients Per Site: 10.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the short-term antiviral potency of GS-9131 functional monotherapy compared to placebo-to-match (PTM) GS-9131, each administered once daily with the existing failing antiretroviral (ARV) regimen as demonstrated by the proportion of participants achieving human immunodeficiency virus ribonucleic acid (HIV-1 RNA) > 0.5 log10 decreases from baseline after up to 14 days of therapy in HIV-1 positive, ARV treatment experienced adult participants with nucleos(t)ide resistant virus.

This is a two-part study. Part 1 consists of three cohorts: 2 Sentinel Cohorts and 1 Randomized Cohort. Eligible participants from Part 1 will proceed to Part 2 followed by an optional open-label extension.

Condition or Disease	Intervention/Treatment	Phase
HIV-1-infection	Drug: GS-9131; Drug: BIC; Drug: TAF; Drug: ARV regimen; Drug: DRV; Drug: RTV	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study to Evaluate the Efficacy of GS-9131 Functional Monotherapy in HIV-1-Infected Adults Failing a Nucleos(t)Ide Reverse Transcriptase Inhibitor-Containing Regimen With Nucleos(t)Ide Reverse Transcriptase Inhibitor Resistant Virus
• Actual Study Start Date: Apr 3, 2018
• Actual Primary Completion Date: Dec 9, 2019
• Actual Study Completion Date: Dec 9, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Sentinel Cohort 1: GS-9131 60 mg Treatment experienced participants will receive GS-9131 60 mg in addition to their current failing ARV regimen for a period of 10 days.	Drug: GS-9131; Tablet(s) administered orally once daily; Drug: ARV regimen; ARV regimen may consist of the ARV agents containing nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitor (NNRTI)
Experimental: Part 1 Sentinel Cohort 2: GS-9131 180 mg Treatment experienced participants will receive GS-9131 180 mg in addition to their current failing ARV regimen for a period of 14 days.	Drug: GS-9131; Tablet(s) administered orally once daily; Drug: ARV regimen; ARV regimen may consist of the ARV agents containing nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitor (NNRTI)
Experimental: Part 1: Randomized Cohort Participants will be randomized in 1:1:1:1 so as to receive GS-9131 in 3 active dose levels up to a maximum of 180 mg or Placebo to match GS-9131 in addition to their current failing ARV regimen for a period of 14 days in Part 1.	Drug: GS-9131; Tablet(s) administered orally once daily; Drug: ARV regimen; ARV regimen may consist of the ARV agents containing nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitor (NNRTI)
Experimental: Part 2 Sentinel Cohort 1: GS-9131 + BIC + DRV + RTV Participants who complete dosing in Sentinel Cohort 1 of Part 1 and show a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 11 and discontinue their current failing regimen will receive an optimized regimen consisting of GS-9131 60 mg + bictegravir (BIC) 30 mg + darunavir (DRV) 800 mg + ritonavir (RTV) 100 mg for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 60 mg + BIC 75 mg + tenofovir alafenamide (TAF) 25 mg, for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurs first.	Drug: GS-9131; Tablet(s) administered orally once daily; Drug: BIC; Tablet(s) administered orally once daily; Drug: DRV; Tablet(s) administered orally once daily; Other Names: Prezista® ; Drug: RTV; Tablet(s) administered orally once daily; Other Names: Norvir®
Experimental: Part 2 Sentinel Cohort 2: GS-9131 + BIC + TAF Participants who complete dosing in Sentinel Cohort 2 of Part 1 and show a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 15 and discontinue their current failing regimen will receive an optimized regimen consisting of GS-9131 180 mg + BIC 75 mg + TAF 25 mg, for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 180 mg + BIC 75 mg + TAF 25 mg, for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurs first.	Drug: GS-9131; Tablet(s) administered orally once daily; Drug: BIC; Tablet(s) administered orally once daily; Drug: TAF; Tablet(s) administered orally once daily; Other Names: Vemlidy®

Outcome Measures

Primary Outcome Measures

1. Part 1 Randomized Cohort: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 15 [Day 15]

   The criteria for analyzing percentage of participants with plasma HIV-1 RNA > 0.5 log10 decrease from baseline in randomized cohort was at least 50% of the participants should achieve HIV-1 RNA > 0.5 log10 decrease from baseline in the Part 1 sentinel cohort 2.

Secondary Outcome Measures

1. Part 1 Sentinel Cohort 1: Change From Baseline in Plasma log10 HIV-1 RNA at Day 11 [Baseline, Day 11]

2. Part 1 Sentinel Cohort 2: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15 [Baseline, Day 15]

3. Part 1 Randomized Cohort: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15 [Baseline, Day 15]

4. Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24 [Week 24]

   The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

5. Part 2: Change From Baseline in Plasma log10 HIV-1 RNA at Week 24 [Baseline, Week 24]

6. Part 2: Change From Baseline in CD4+ Cell Count at Week 24 [Baseline, Week 24]

7. Part 2: Number of Participants With Treatment Emergent Nucleos(t)Ide Reverse Transcriptase Inhibitor (NRTI) Mutations at the Time of Virologic Failure [From first dose up to Week 24]

   Treatment emergent virological failure was defined as an event with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of the study drug. Virologic failure was defined as virologic rebound or as suboptimal virologic response in relation to pre-GS-9131 baseline plasma HIV-1 RNA levels. Virological rebound was defined as if participant at any visit after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA ≥ 50 copies/mL, or a >1 log10 increase in HIV-1 RNA from the nadir which was subsequently confirmed at the following scheduled or unscheduled visit. Suboptimal virologic response was defined as plasma HIV-1 RNA ≥ 200 copies/mL and reduction in HIV-1 RNA ≤ 1 log10 from pre-GS-9131 baseline at the Week 8 visit with confirmation at the next scheduled or unscheduled visit.

8. Part 2: Number of Participants With Treatment Emergent Protease Inhibitor (PI) Mutations at the Time of Virologic Failure [From first dose up to Week 24]

   Treatment emergent virological failure was defined as an event with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of the study drug. Virologic failure was defined as virologic rebound or as suboptimal virologic response in relation to pre-GS-9131 baseline plasma HIV-1 RNA levels. Virological rebound was defined as if participant at any visit after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA ≥ 50 copies/mL, or a >1 log10 increase in HIV-1 RNA from the nadir which was subsequently confirmed at the following scheduled or unscheduled visit. Suboptimal virologic response was defined as plasma HIV-1 RNA ≥ 200 copies/mL and reduction in HIV-1 RNA ≤ 1 log10 from pre-GS-9131 baseline at the Week 8 visit with confirmation at the next scheduled or unscheduled visit.

9. Part 2: Number of Participants With Treatment Emergent Integrase Strand Transfer Inhibitor (INSTI) Mutations at the Time of Virologic Failure [From first dose up to Week 24]

   Treatment emergent virological failure was defined as an event with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of the study drug. Virologic failure was defined as virologic rebound or as suboptimal virologic response in relation to pre-GS-9131 baseline plasma HIV-1 RNA levels. Virological rebound was defined as if participant at any visit after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA ≥ 50 copies/mL, or a >1 log10 increase in HIV-1 RNA from the nadir which was subsequently confirmed at the following scheduled or unscheduled visit. Suboptimal virologic response was defined as plasma HIV-1 RNA ≥ 200 copies/mL and reduction in HIV-1 RNA ≤ 1 log10 from pre-GS-9131 baseline at the Week 8 visit with confirmation at the next scheduled or unscheduled visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Plasma HIV-1 RNA ≥ 500 copies/mL at screening Visit

• Currently taking a failing ARV regimen that contains 2 NRTIs and a NNRTI

• No prior or current ARV regimens containing integrase inhibitor (INSTI) or protease inhibitor (PI)

• Screening genotype must show at least the protocol defined resistance mutation profile

Key Exclusion Criteria:

• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1

• Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial

• Use of an investigational drug other than the study drug

• Individuals with chronic hepatitis B virus (HBV) infection are not permitted to participate

• Active tuberculosis infection

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Joint Clinical Research Centre	Kampala		Uganda	10005
2	Joint Research Ethics Committee for the University of Zimbabwe College of Health Sciences and Parirenyatwa Group of Hospitals	Harare		Zimbabwe

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol - Nov 1, 2018
• Statistical Analysis Plan - Mar 3, 2020

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT03472326
• Other Study ID Numbers: GS-US-442-4148
• First Posted: Mar 21, 2018
• Last Update Posted: Jan 5, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: GS-9131

Study Results

Participant Flow

Recruitment Details

Participants were enrolled at study sites in Uganda and Zimbawe. The first participant was screened on 03 April 2018. The last study visit occurred on 09 December 2019.

Pre-assignment Detail

88 participants were screened. The study was conducted in 2 parts. The Part 1 consisted of 3 cohorts- 2 Sentinel Cohorts and 1 Randomized Cohort and Part 2 consisted of 2 Sentinel Cohorts only. The Randomized Cohort in Part 1 was not initiated. The study was terminated because a majority of Sentinel Cohort 2 (Part 1) participants did not meet primary endpoint of human immunodeficiency virus ribonucleic acid (HIV-1 RNA) > 0.5 log10 decrease from baseline in through up to 14 days of therapy.

Arm/Group Title	Part 1 Sentinel Cohort 1: GS-9131 60 mg	Part 1 Sentinel Cohort 2: GS-9131 180 mg	Part 2 Sentinel Cohort 1: GS-9131 + BIC + DRV + RTV	Part 2 Sentinel Cohort 2: GS-9131 + BIC + TAF
Arm/Group Description	Participants received GS-9131 60 mg tablets orally once daily in addition to their current failing antiretroviral (ARV) regimen for a period of 10 days.	Participants received GS-9131 180 mg tablets orally once daily in addition to their current failing ARV regimen for a period of 14 days.	Participants who completed dosing in Sentinel Cohort 1 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 11 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 60 mg tablets + bictegravir (BIC) 30 mg tablets + darunavir (DRV) 800 mg tablets + ritonavir (RTV) 100 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants had the option to participate in an open label extension and receive GS-9131 60 mg tablets + BIC 75 mg tablets + tenofovir alafenamide (TAF) 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.	Participants who completed dosing in Sentinel Cohort 2 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 15 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants had the option to participate in an open label extension and receive GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.
Period Title: Part 1: GS-9131 Functional Monotherapy
STARTED	11	10	0	0
COMPLETED	11	10	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1: GS-9131 Functional Monotherapy
STARTED	0	0	1	3
COMPLETED	0	0	0	0
NOT COMPLETED	0	0	1	3

Baseline Characteristics

Arm/Group Title	Sentinel Cohort 1: GS-9131 60 mg	Sentinel Cohort 2: GS-9131 180 mg	Total
Arm/Group Description	Participants in Sentinel Cohort 1 received GS-9131 60 mg tablets orally once daily in addition to their current failing ARV regimen for a period of 10 days in Part 1.	Participants in Sentinel Cohort 2 received GS-9131 180 mg tablets orally once daily in addition to their current failing ARV regimen for a period of 14 days in Part 1.	Total of all reporting groups
Overall Participants	11	10	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38 (10.7)	37 (6.6)	38 (8.8)
Sex: Female, Male (Count of Participants)
Female	11 100%	10 100%	21 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	11 100%	10 100%	21 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	11 100%	10 100%	21 100%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Uganda	11 100%	5 50%	16 76.2%
Zimbabwe	0 0%	5 50%	5 23.8%
HIV-1 RNA (log10 copies/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 copies/mL]	4.77 (0.703)	4.46 (0.584)	4.62 (0.652)
HIV-1 RNA Category (Count of Participants)
< 50 copies/mL	0 0%	0 0%	0 0%
≥ 50 copies/mL	11 100%	10 100%	21 100%
CD4 Cell Count (cells/µL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/µL]	172 (164.1)	289 (140.4)	228 (161.0)

Outcome Measures

1. Primary Outcome

Title	Part 1 Randomized Cohort: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 15
Description	The criteria for analyzing percentage of participants with plasma HIV-1 RNA > 0.5 log10 decrease from baseline in randomized cohort was at least 50% of the participants should achieve HIV-1 RNA > 0.5 log10 decrease from baseline in the Part 1 sentinel cohort 2.
Time Frame	Day 15

Outcome Measure Data

Analysis Population Description

Data was not analyzed as ≥ 50% participants did not achieve HIV-1 RNA > 0.5 log10 decrease from baseline in Part 1 sentinel cohort 2.

Arm/Group Title	Part 1: Randomized Cohort
Arm/Group Description	Participants were randomized in 1:1:1:1 so as to receive GS-9131 tablets orally once daily in 3 active dose levels up to a maximum of 180 mg or Placebo to match GS-9131 tablets orally once daily in addition to their current failing ARV regimen for a period of 14 days in Part 1.
Measure Participants	0

2. Secondary Outcome

Title	Part 1 Sentinel Cohort 1: Change From Baseline in Plasma log10 HIV-1 RNA at Day 11
Time Frame	Baseline, Day 11

Outcome Measure Data

Analysis Population Description

The Safety Analysis Set included all participants who took at least 1 dose of study medication.

Arm/Group Title	Sentinel Cohort 1: GS-9131 60 mg
Arm/Group Description	Participants in Sentinel Cohort 1 received GS-9131 60 mg tablets orally once daily in addition to their current failing ARV regimen for a period of 10 days in Part 1.
Measure Participants	11
Mean (Standard Deviation) [log10 copies/mL]	-0.13 (0.268)

3. Secondary Outcome

Title	Part 1 Sentinel Cohort 2: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	Sentinel Cohort 2: GS-9131 180 mg
Arm/Group Description	Participants in Sentinel Cohort 2 received GS-9131 180 mg tablets orally once daily in addition to their current failing ARV regimen for a period of 14 days in Part 1.
Measure Participants	8
Mean (Standard Deviation) [log10 copies/mL]	-0.29 (0.207)

4. Secondary Outcome

Title	Part 1 Randomized Cohort: Change From Baseline in Plasma log10 HIV-1 RNA at Day 15
Time Frame	Baseline, Day 15

Outcome Measure Data

Analysis Population Description

Data was not reported as the Randomized Cohort in Part 1 was not initiated as the study was terminated early because a majority of Sentinel Cohort 2 participants did not meet primary endpoint of HIV-1 RNA > 0.5 log10 decrease from baseline in through up to 14 days of therapy.

Arm/Group Title	Part 1: Randomized Cohort
Arm/Group Description	Participants were randomized in 1:1:1:1 so as to receive GS-9131 tablets orally once daily in 3 active dose levels up to a maximum of 180 mg or Placebo to match GS-9131 tablets orally once daily in addition to their current failing ARV regimen for a period of 14 days in Part 1.
Measure Participants	0

5. Secondary Outcome

Title	Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24
Description	The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Data were collected for only 1 participant, and due to participant confidentiality data is not being reported.

Arm/Group Title	Part 2: GS-9131 + BIC + DRV + RTV	Part 2: GS-9131 + BIC + TAF
Arm/Group Description	Participants who completed dosing in Sentinel Cohort 1 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 11 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 60 mg tablets + BIC 30 mg tablets + DRV 800 mg tablets + RTV 100 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 60 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.	Participants who completed dosing in Sentinel Cohort 2 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 15 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.
Measure Participants	0	0

6. Secondary Outcome

Title	Part 2: Change From Baseline in Plasma log10 HIV-1 RNA at Week 24
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Data were collected for only 1 participant, and due to participant confidentiality data is not being reported.

Arm/Group Title	Part 2: GS-9131 + BIC + DRV + RTV	Part 2: GS-9131 + BIC + TAF
Arm/Group Description	Participants who completed dosing in Sentinel Cohort 1 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 11 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 60 mg tablets + BIC 30 mg tablets + DRV 800 mg tablets + RTV 100 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 60 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.	Participants who completed dosing in Sentinel Cohort 2 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 15 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.
Measure Participants	0	0

7. Secondary Outcome

Title	Part 2: Change From Baseline in CD4+ Cell Count at Week 24
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Data were collected for only 1 participant, and due to participant confidentiality data is not being reported.

Arm/Group Title	Part 2: GS-9131 + BIC + DRV + RTV	Part 2: GS-9131 + BIC + TAF
Arm/Group Description	Participants who completed dosing in Sentinel Cohort 1 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 11 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 60 mg tablets + BIC 30 mg tablets + DRV 800 mg tablets + RTV 100 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 60 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.	Participants who completed dosing in Sentinel Cohort 2 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 15 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.
Measure Participants	0	0

8. Secondary Outcome

Title	Part 2: Number of Participants With Treatment Emergent Nucleos(t)Ide Reverse Transcriptase Inhibitor (NRTI) Mutations at the Time of Virologic Failure
Description	Treatment emergent virological failure was defined as an event with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of the study drug. Virologic failure was defined as virologic rebound or as suboptimal virologic response in relation to pre-GS-9131 baseline plasma HIV-1 RNA levels. Virological rebound was defined as if participant at any visit after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA ≥ 50 copies/mL, or a >1 log10 increase in HIV-1 RNA from the nadir which was subsequently confirmed at the following scheduled or unscheduled visit. Suboptimal virologic response was defined as plasma HIV-1 RNA ≥ 200 copies/mL and reduction in HIV-1 RNA ≤ 1 log10 from pre-GS-9131 baseline at the Week 8 visit with confirmation at the next scheduled or unscheduled visit.
Time Frame	From first dose up to Week 24

Outcome Measure Data

Analysis Population Description

Due to early study termination, data were not collected as none of the participants qualified for resistance testing after Week 8.

Arm/Group Title	Part 2: GS-9131 + BIC + DRV + RTV	Part 2: GS-9131 + BIC + TAF
Arm/Group Description	Participants who completed dosing in Sentinel Cohort 1 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 11 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 60 mg tablets + BIC 30 mg tablets + DRV 800 mg tablets + RTV 100 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 60 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.	Participants who completed dosing in Sentinel Cohort 2 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 15 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.
Measure Participants	0	0

9. Secondary Outcome

Title	Part 2: Number of Participants With Treatment Emergent Protease Inhibitor (PI) Mutations at the Time of Virologic Failure
Description	Treatment emergent virological failure was defined as an event with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of the study drug. Virologic failure was defined as virologic rebound or as suboptimal virologic response in relation to pre-GS-9131 baseline plasma HIV-1 RNA levels. Virological rebound was defined as if participant at any visit after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA ≥ 50 copies/mL, or a >1 log10 increase in HIV-1 RNA from the nadir which was subsequently confirmed at the following scheduled or unscheduled visit. Suboptimal virologic response was defined as plasma HIV-1 RNA ≥ 200 copies/mL and reduction in HIV-1 RNA ≤ 1 log10 from pre-GS-9131 baseline at the Week 8 visit with confirmation at the next scheduled or unscheduled visit.
Time Frame	From first dose up to Week 24

Outcome Measure Data

Analysis Population Description

Due to early study termination, data were not collected as none of the participants qualified for resistance testing after Week 8.

Arm/Group Title	Part 2: GS-9131 + BIC + DRV + RTV	Part 2: GS-9131 + BIC + TAF
Arm/Group Description	Participants who completed dosing in Sentinel Cohort 1 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 11 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 60 mg tablets + BIC 30 mg tablets + DRV 800 mg tablets + RTV 100 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 60 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.	Participants who completed dosing in Sentinel Cohort 2 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 15 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.
Measure Participants	0	0

10. Secondary Outcome

Title	Part 2: Number of Participants With Treatment Emergent Integrase Strand Transfer Inhibitor (INSTI) Mutations at the Time of Virologic Failure
Description	Treatment emergent virological failure was defined as an event with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of the study drug. Virologic failure was defined as virologic rebound or as suboptimal virologic response in relation to pre-GS-9131 baseline plasma HIV-1 RNA levels. Virological rebound was defined as if participant at any visit after achieving HIV-1 RNA < 50 copies/mL, a rebound in HIV-1 RNA ≥ 50 copies/mL, or a >1 log10 increase in HIV-1 RNA from the nadir which was subsequently confirmed at the following scheduled or unscheduled visit. Suboptimal virologic response was defined as plasma HIV-1 RNA ≥ 200 copies/mL and reduction in HIV-1 RNA ≤ 1 log10 from pre-GS-9131 baseline at the Week 8 visit with confirmation at the next scheduled or unscheduled visit.
Time Frame	From first dose up to Week 24

Outcome Measure Data

Analysis Population Description

Due to early study termination, data were not collected as none of the participants qualified for resistance testing after Week 8.

Arm/Group Title	Part 2: GS-9131 + BIC + DRV + RTV	Part 2: GS-9131 + BIC + TAF
Arm/Group Description	Participants who completed dosing in Sentinel Cohort 1 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 11 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 60 mg tablets + BIC 30 mg tablets + DRV 800 mg tablets + RTV 100 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 60 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.	Participants who completed dosing in Sentinel Cohort 2 and showed a reduction in plasma HIV RNA > 0.5 log10 from their pre-GS-9131 baseline value at Day 15 and discontinued their current failing regimen received an optimized regimen consisting of GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for a period of 24 weeks. After Week 24, participants will be given the option to participate in an open label extension and receive GS-9131 180 mg tablets + BIC 75 mg tablets + TAF 25 mg tablets, orally once daily for an additional 24 weeks or until Gilead Sciences elects to discontinue the study drug in that country, whichever occurred first.
Measure Participants	0	0

Adverse Events

Time Frame	From first dose date up to 30 days after last study drug for Part 1 (Maximum: 44 days)
Adverse Event Reporting Description	The Safety Analysis Set included all participants (in Sentinal Cohorts 1 and 2 in part 1) who took at least 1 dose of study medication. Due to the early discontinuation of the study, safety analyses were performed for Sentinel Cohorts in Part 1 only. In Part 2, Data were collected for only 1 participant, and due to participant confidentiality data is not being reported.
Arm/Group Title	Part 1 Setinel Cohort 1: GS-9131 60 mg		Part 1 Sentinel Cohort 2: GS-9131 180 mg
Arm/Group Description	Participants in Sentinel Cohort 1 received GS-9131 60 mg tablets orally once daily in addition to their current failing ARV regimen for a period of 10 days in Part 1.		Participants in Sentinel Cohort 2 received GS-9131 180 mg tablets orally once daily in addition to their current failing ARV regimen for a period of 14 days in Part 1.
All Cause Mortality
	Part 1 Setinel Cohort 1: GS-9131 60 mg		Part 1 Sentinel Cohort 2: GS-9131 180 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/10 (0%)
Serious Adverse Events
	Part 1 Setinel Cohort 1: GS-9131 60 mg		Part 1 Sentinel Cohort 2: GS-9131 180 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Part 1 Setinel Cohort 1: GS-9131 60 mg		Part 1 Sentinel Cohort 2: GS-9131 180 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/11 (45.5%)		10/10 (100%)
Blood and lymphatic system disorders
Anaemia	1/11 (9.1%)		1/10 (10%)
Neutropenia	1/11 (9.1%)		0/10 (0%)
Neutrophilia	0/11 (0%)		1/10 (10%)
Gastrointestinal disorders
Abdominal hernia	0/11 (0%)		1/10 (10%)
Abdominal pain	0/11 (0%)		1/10 (10%)
Abdominal tenderness	0/11 (0%)		1/10 (10%)
Diarrhoea	0/11 (0%)		2/10 (20%)
Gastritis	0/11 (0%)		1/10 (10%)
Nausea	0/11 (0%)		2/10 (20%)
Toothache	1/11 (9.1%)		1/10 (10%)
Vomiting	0/11 (0%)		2/10 (20%)
General disorders
Malaise	1/11 (9.1%)		1/10 (10%)
Oedema peripheral	0/11 (0%)		1/10 (10%)
Pain	0/11 (0%)		1/10 (10%)
Infections and infestations
Cellulitis	1/11 (9.1%)		0/10 (0%)
Conjunctivitis	0/11 (0%)		1/10 (10%)
Influenza	0/11 (0%)		1/10 (10%)
Oral herpes	0/11 (0%)		1/10 (10%)
Pharyngitis	0/11 (0%)		1/10 (10%)
Rhinitis	1/11 (9.1%)		1/10 (10%)
Upper respiratory tract infection	1/11 (9.1%)		1/10 (10%)
Urinary tract infection	1/11 (9.1%)		3/10 (30%)
Vulvovaginal candidiasis	0/11 (0%)		1/10 (10%)
Investigations
Amylase increased	0/11 (0%)		1/10 (10%)
Metabolism and nutrition disorders
Decreased appetite	0/11 (0%)		1/10 (10%)
Increased appetite	0/11 (0%)		3/10 (30%)
Musculoskeletal and connective tissue disorders
Myalgia	0/11 (0%)		1/10 (10%)
Nervous system disorders
Dizziness	0/11 (0%)		3/10 (30%)
Headache	1/11 (9.1%)		2/10 (20%)
Hypersomnia	0/11 (0%)		4/10 (40%)
Hypoaesthesia	0/11 (0%)		1/10 (10%)
Psychiatric disorders
Insomnia	0/11 (0%)		1/10 (10%)
Pica	0/11 (0%)		1/10 (10%)
Reproductive system and breast disorders
Metrorrhagia	0/11 (0%)		1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Cough	0/11 (0%)		2/10 (20%)
Skin and subcutaneous tissue disorders
Pruritus	0/11 (0%)		1/10 (10%)
Vascular disorders
Thrombophlebitis superficial	0/11 (0%)		1/10 (10%)

Limitations/Caveats

The study was terminated because a majority of Sentinel Cohort 2 participants did not meet primary endpoint of HIV-1 RNA > 0.5 log10 decrease from baseline through up to 14 days of therapy.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years