Trial Outcomes & Findings for The Late Presenter Treatment Optimisation Study (NCT NCT03696160)

Last Updated: 2025-12-17

Results Overview

Composite outcome: treatment failure due to either virological or clinical reasons. Virological reasons can either be insufficient virological response or viral rebound. Clinical reasons can be death related to HIV/AIDS/opportunistic infection or severe bacterial infection, new or recurrent AIDS defining event, any serious non-AIDS defining event or clinically relevant adverse events of any grade or immune reconstitution inflammatory syndrome requiring treatment

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

447 participants

Primary outcome timeframe

Earliest at 12 weeks, latest 48 weeks

Results posted on

2025-12-17

Participant Flow

Number of Subjects Enrolled: 447

Number of Subjects Screened: 475

Participant milestones

Participant milestones
Measure	Biktarvy Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food.	Symtuza Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food.
Overall Study STARTED	222	225
Overall Study COMPLETED	220	222
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Biktarvy Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food.	Symtuza Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food.
Overall Study Withdrew before IMP dosing	2	3

Baseline Characteristics

The Late Presenter Treatment Optimisation Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food.	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food.	Total n=442 Participants Total of all reporting groups
Age, Continuous	44 Years n=6 Participants	42 Years n=5 Participants	43 Years n=5 Participants
Sex: Female, Male Female	40 Participants n=6 Participants	44 Participants n=5 Participants	84 Participants n=5 Participants
Sex: Female, Male Male	180 Participants n=6 Participants	178 Participants n=5 Participants	358 Participants n=5 Participants
Region of Enrollment United Kingdom	45 Participants n=6 Participants	42 Participants n=5 Participants	87 Participants n=5 Participants
Region of Enrollment Spain	61 Participants n=6 Participants	61 Participants n=5 Participants	122 Participants n=5 Participants
Region of Enrollment France	30 Participants n=6 Participants	32 Participants n=5 Participants	62 Participants n=5 Participants
Region of Enrollment Belgium	17 Participants n=6 Participants	17 Participants n=5 Participants	34 Participants n=5 Participants
Region of Enrollment Italy	28 Participants n=6 Participants	30 Participants n=5 Participants	58 Participants n=5 Participants
Region of Enrollment Germany	37 Participants n=6 Participants	38 Participants n=5 Participants	75 Participants n=5 Participants
Region of Enrollment Ireland	2 Participants n=6 Participants	2 Participants n=5 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	43 Participants n=6 Participants	40 Participants n=5 Participants	83 Participants n=5 Participants
Race (NIH/OMB) White	140 Participants n=6 Participants	136 Participants n=5 Participants	276 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	37 Participants n=6 Participants	46 Participants n=5 Participants	83 Participants n=5 Participants

PRIMARY outcome

Timeframe: Earliest at 12 weeks, latest 48 weeks

Population: Each row represents a different analysis using different patient numbers, dependent on mITT or PP analysis

Outcome measures

Outcome measures
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food. Biktarvy: Integrase inhibitor used to treat HIV-1 infection	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food. Symtuza: Protease inhibitor used to treat HIV-1 infection
Treatment Failure mITT analysis	49 Participants	70 Participants
Treatment Failure PP analysis	48 Participants	69 Participants

SECONDARY outcome

Timeframe: Week 24, 36 and 48

at week 24, 36, 48

Outcome measures

Outcome measures
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food. Biktarvy: Integrase inhibitor used to treat HIV-1 infection	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food. Symtuza: Protease inhibitor used to treat HIV-1 infection
Proportion of Patients With HIV-RNA Viral Load <50 Copies/mL <50 at Week 48	151 Participants	136 Participants
Proportion of Patients With HIV-RNA Viral Load <50 Copies/mL <50 at Week 24	127 Participants	112 Participants
Proportion of Patients With HIV-RNA Viral Load <50 Copies/mL <50 at Week 36	135 Participants	134 Participants

SECONDARY outcome

Timeframe: Through study completion, up to 48 weeks.

Outcome measures

Outcome measures
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food. Biktarvy: Integrase inhibitor used to treat HIV-1 infection	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food. Symtuza: Protease inhibitor used to treat HIV-1 infection
Time to Reach CD4 (Cluster of Differentiation 4) Count >200/µL CD4 >200 W36	110 Participants	114 Participants
Time to Reach CD4 (Cluster of Differentiation 4) Count >200/µL CD4 >200 W0	9 Participants	8 Participants
Time to Reach CD4 (Cluster of Differentiation 4) Count >200/µL CD4 >200 W48	115 Participants	121 Participants
Time to Reach CD4 (Cluster of Differentiation 4) Count >200/µL CD4 >200 W4	65 Participants	58 Participants
Time to Reach CD4 (Cluster of Differentiation 4) Count >200/µL CD4 >200 W8	72 Participants	65 Participants
Time to Reach CD4 (Cluster of Differentiation 4) Count >200/µL CD4 >200 W12	74 Participants	71 Participants
Time to Reach CD4 (Cluster of Differentiation 4) Count >200/µL CD4 >200 W24	87 Participants	91 Participants

SECONDARY outcome

Timeframe: 4, 8, 12, 24, 36, 48 weeks

Population: Number analysed differs due to: * some CD4 tests missed at visit * some patients withdraw/miss visits

Outcome measures

Outcome measures
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food. Biktarvy: Integrase inhibitor used to treat HIV-1 infection	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food. Symtuza: Protease inhibitor used to treat HIV-1 infection
Proportion of Patients With CD4 Cell Count <200 and < 350μL at Week 4, 8, 12, 24, 36, 48 <200 at W12	116 Participants	133 Participants
Proportion of Patients With CD4 Cell Count <200 and < 350μL at Week 4, 8, 12, 24, 36, 48 <200 at W24	101 Participants	107 Participants
Proportion of Patients With CD4 Cell Count <200 and < 350μL at Week 4, 8, 12, 24, 36, 48 <200 at W36	76 Participants	81 Participants
Proportion of Patients With CD4 Cell Count <200 and < 350μL at Week 4, 8, 12, 24, 36, 48 <200 at W48	64 Participants	65 Participants
Proportion of Patients With CD4 Cell Count <200 and < 350μL at Week 4, 8, 12, 24, 36, 48 <350 at W4	185 Participants	195 Participants
Proportion of Patients With CD4 Cell Count <200 and < 350μL at Week 4, 8, 12, 24, 36, 48 <350 at W8	162 Participants	187 Participants
Proportion of Patients With CD4 Cell Count <200 and < 350μL at Week 4, 8, 12, 24, 36, 48 <350 at W12	165 Participants	190 Participants
Proportion of Patients With CD4 Cell Count <200 and < 350μL at Week 4, 8, 12, 24, 36, 48 <200 at W4	136 Participants	153 Participants
Proportion of Patients With CD4 Cell Count <200 and < 350μL at Week 4, 8, 12, 24, 36, 48 <200 at W8	114 Participants	136 Participants
Proportion of Patients With CD4 Cell Count <200 and < 350μL at Week 4, 8, 12, 24, 36, 48 <350 at W24	160 Participants	180 Participants
Proportion of Patients With CD4 Cell Count <200 and < 350μL at Week 4, 8, 12, 24, 36, 48 <350 at W36	152 Participants	161 Participants
Proportion of Patients With CD4 Cell Count <200 and < 350μL at Week 4, 8, 12, 24, 36, 48 <350 at W48	137 Participants	151 Participants

SECONDARY outcome

Timeframe: Week 4, 8, 12, 24, 36, 48

Population: Number analysed differs due to: * some CD4:CD8 tests missed at visit * some patients withdraw/miss visits

CD4/CD8 ratio at week 4, 8, 12, 24, 36, 48

Outcome measures

Outcome measures
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food. Biktarvy: Integrase inhibitor used to treat HIV-1 infection	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food. Symtuza: Protease inhibitor used to treat HIV-1 infection
CD4/CD8 (Cluster of Differentiation 8) Ratio Week 36	0.31 Ratio Standard Error 0.01	0.28 Ratio Standard Error 0.01
CD4/CD8 (Cluster of Differentiation 8) Ratio Week 48	0.33 Ratio Standard Error 0.01	0.31 Ratio Standard Error 0.01
CD4/CD8 (Cluster of Differentiation 8) Ratio Week 0	0.11 Ratio Standard Error 0.01	0.11 Ratio Standard Error 0.01
CD4/CD8 (Cluster of Differentiation 8) Ratio Week 4	0.2 Ratio Standard Error 0.01	0.18 Ratio Standard Error 0.01
CD4/CD8 (Cluster of Differentiation 8) Ratio Week 8	0.2 Ratio Standard Error 0.01	0.19 Ratio Standard Error 0.01
CD4/CD8 (Cluster of Differentiation 8) Ratio Week 12	0.22 Ratio Standard Error 0.01	0.2 Ratio Standard Error 0.01
CD4/CD8 (Cluster of Differentiation 8) Ratio Week 24	0.27 Ratio Standard Error 0.01	0.25 Ratio Standard Error 0.01

SECONDARY outcome

Timeframe: Week 48

Incidence of Immune Reconstitution Inflammatory Syndrome

Outcome measures

Outcome measures
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food. Biktarvy: Integrase inhibitor used to treat HIV-1 infection	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food. Symtuza: Protease inhibitor used to treat HIV-1 infection
Incidence of Immune Reconstitution Inflammatory Syndrome	7 Participants	8 Participants

SECONDARY outcome

Timeframe: Week 48

Start/Stop of hospitalization for any reason Start/Stop of opportunistic infections as listed within Appendix 3 (AIDS defining events according to https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5710a2.htm) Start/Stop of severe BI, which consists of any of bacterial pneumonia, invasive bacterial infection (IBI) or any bacterial infectious disorder with grade 3 severity or requiring unscheduled hospital admission. An IBI is defined as the isolation of a bacterial organism from a normally sterile body site, or for bacterial nucleic acid to be detected at a normally sterile body site. Sterile body sites include blood, cerebrospinal fluid, pleural fluid, pericardial fluid, peritoneal fluid, joint fluid, bone aspirate, or a deep tissue abscess.

Outcome measures

Outcome measures
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food. Biktarvy: Integrase inhibitor used to treat HIV-1 infection	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food. Symtuza: Protease inhibitor used to treat HIV-1 infection
Number of Participants With Hospitalisation or Relapse of Specific Opportunistic or Bacterial Infection	41 Participants	53 Participants

SECONDARY outcome

Timeframe: Week 48

Outcome measures

Outcome measures
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food. Biktarvy: Integrase inhibitor used to treat HIV-1 infection	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food. Symtuza: Protease inhibitor used to treat HIV-1 infection
Number of Participants With Treatment-related Adverse Events as Assessed by Division of AIDS Adverse Event (AE) Grading Table Corrected Version 2.1-July 2017 Grade 2 AE's	111 Participants	127 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by Division of AIDS Adverse Event (AE) Grading Table Corrected Version 2.1-July 2017 Grade 3 AE's	37 Participants	46 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by Division of AIDS Adverse Event (AE) Grading Table Corrected Version 2.1-July 2017 Grade 4 AE's	18 Participants	13 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by Division of AIDS Adverse Event (AE) Grading Table Corrected Version 2.1-July 2017 Any AE's ≥Grade 2	124 Participants	139 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by Division of AIDS Adverse Event (AE) Grading Table Corrected Version 2.1-July 2017 Grade 3 or 4 AE's	47 Participants	52 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by Division of AIDS Adverse Event (AE) Grading Table Corrected Version 2.1-July 2017 Drug-Related AE's ≥Grade 2	16 Participants	32 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by Division of AIDS Adverse Event (AE) Grading Table Corrected Version 2.1-July 2017 Drug-Related AE's Grade 3 or 4	3 Participants	4 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by Division of AIDS Adverse Event (AE) Grading Table Corrected Version 2.1-July 2017 AE's leading to study drug interruption	16 Participants	18 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by Division of AIDS Adverse Event (AE) Grading Table Corrected Version 2.1-July 2017 SAE's	48 Participants	52 Participants
Number of Participants With Treatment-related Adverse Events as Assessed by Division of AIDS Adverse Event (AE) Grading Table Corrected Version 2.1-July 2017 Death	9 Participants	3 Participants

SECONDARY outcome

Timeframe: Week 48

Antiretroviral therapy and opportunistic or bacterial infection treatment changes and dose modifications due to toxicities and drug-drug interaction with antiretroviral therapy, and Immune Reconstitution Inflammatory Syndrome

Outcome measures

Outcome measures
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food. Biktarvy: Integrase inhibitor used to treat HIV-1 infection	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food. Symtuza: Protease inhibitor used to treat HIV-1 infection
ART and OI/BI Treatment Changes and Dose Modifications Due to Toxicities and DDI With ART, and IRIS Through Week 48 ART change or study discontinuation due to toxicities	11 Participants	12 Participants
ART and OI/BI Treatment Changes and Dose Modifications Due to Toxicities and DDI With ART, and IRIS Through Week 48 ART change or study discontinuation due to IRIS	2 Participants	1 Participants
ART and OI/BI Treatment Changes and Dose Modifications Due to Toxicities and DDI With ART, and IRIS Through Week 48 ART change or study discontinuation due to DDI	10 Participants	6 Participants
ART and OI/BI Treatment Changes and Dose Modifications Due to Toxicities and DDI With ART, and IRIS Through Week 48 % of participants with ART change or study discontinuation due to toxicities, DDI, or IRIS	23 Participants	19 Participants

SECONDARY outcome

Timeframe: Week 48

Outcome measures

Outcome measures
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food. Biktarvy: Integrase inhibitor used to treat HIV-1 infection	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food. Symtuza: Protease inhibitor used to treat HIV-1 infection
Health Care Resource Use, Including Number of Participants With Critical Care and Emergency Room Visits Incidence of critical care admission	3 Participants	2 Participants
Health Care Resource Use, Including Number of Participants With Critical Care and Emergency Room Visits Incidence of emergency room	28 Participants	33 Participants

SECONDARY outcome

Timeframe: Week 48

EQ-5D-3L (European Quality of life - 5 Dimensions - 3 Levels) and HIV Symptoms Index questionnaires will be completed by patients throughout the study to assess any change throughout their treatment Quality of life (EQ-5D-3L questionnaire) Scale is VAS Score which runs from 0 (worst health imaginable) to 100 (best health imaginable). We report the mean change from Baseline to W48. The HIV Symptom Index score is the sum of frequency ratings for the 20 selected symptoms; the score could range from 0 to 80 (80 being worst score). We report the mean change from Baseline to W48.

Outcome measures

Outcome measures
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food. Biktarvy: Integrase inhibitor used to treat HIV-1 infection	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food. Symtuza: Protease inhibitor used to treat HIV-1 infection
QOL and Functional Status Outcomes, Including Overall Self-reported QOL and Functional Status Compared in the Two Groups at Week 48 Quality of life (EQ-5D-3L questionnaire) Mean difference from Baseline to W48	20.6 Questionnaire Score Standard Error 1.5	16.9 Questionnaire Score Standard Error 1.5
QOL and Functional Status Outcomes, Including Overall Self-reported QOL and Functional Status Compared in the Two Groups at Week 48 HIV Symptoms Index Mean difference from Baseline to W48	-12.0 Questionnaire Score Standard Error 0.9	-9.9 Questionnaire Score Standard Error 0.8

SECONDARY outcome

Timeframe: Week 48

Discontinuation or modification of the single tablet regimen due virological reasons defined as a) Insufficient virological response, either: 1. HIV-1 RNA reduction \< 1 log 10 copies/mL at week 12, or 2. Viral load \> 50 HIV-1 RNA copies/mL at week 48 b) Viral rebound, which is subsequently confirmed at the following scheduled or unscheduled visit, defined as either: a. Rebound of HIV-1 RNA to \>200 copies/mL after having achieved HIV-1 RNA \<50 copies/mL b. Rebound of HIV RNA by \>1 log 10 copies/mL from nadir value, for patients whose viral load has never been suppressed below 50 copies/mL

Outcome measures

Outcome measures
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food. Biktarvy: Integrase inhibitor used to treat HIV-1 infection	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food. Symtuza: Protease inhibitor used to treat HIV-1 infection
Discontinuation or Modification of Study Medication Due to Insufficient Virological Response or Resistance Mutation Development ART change or study discontinuation due to insufficient virological response	1 Participants	0 Participants
Discontinuation or Modification of Study Medication Due to Insufficient Virological Response or Resistance Mutation Development Participants with ART change or discontinuation due to virological response or resistance mutations	3 Participants	1 Participants
Discontinuation or Modification of Study Medication Due to Insufficient Virological Response or Resistance Mutation Development ART change or study discontinuation due to resistance mutations	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Week 48

Duration of hospitalization for any reason

Outcome measures

Outcome measures
Measure	Biktarvy n=220 Participants Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food. Biktarvy: Integrase inhibitor used to treat HIV-1 infection	Symtuza n=222 Participants Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food. Symtuza: Protease inhibitor used to treat HIV-1 infection
Duration of Hospitalisations	10 Days Interval 6.0 to 14.0	13 Days Interval 10.0 to 16.0

Adverse Events

Biktarvy

Serious events: 52 serious events

Other events: 111 other events

Deaths: 9 deaths

Symtuza

Serious events: 54 serious events

Other events: 120 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Project Manager

Research Organisation (KC) Ltd

Phone: +44 (0) 7508 439711

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Biktarvy n=220 participants at risk Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food.	Symtuza n=222 participants at risk Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food.
Respiratory, thoracic and mediastinal disorders Cough	6.8% 15/220 • Number of events 16 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	7.2% 16/222 • Number of events 16 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
Infections and infestations COVID-19	5.9% 13/220 • Number of events 13 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	6.8% 15/222 • Number of events 15 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
Gastrointestinal disorders Diarrhea	5.9% 13/220 • Number of events 14 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	4.1% 9/222 • Number of events 11 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
Gastrointestinal disorders Diarrhoea	5.0% 11/220 • Number of events 11 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	7.7% 17/222 • Number of events 18 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
General disorders Fever	7.3% 16/220 • Number of events 20 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	5.4% 12/222 • Number of events 15 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
Nervous system disorders Headache	9.1% 20/220 • Number of events 23 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	9.9% 22/222 • Number of events 25 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
Vascular disorders Hypertension	7.3% 16/220 • Number of events 17 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	4.5% 10/222 • Number of events 10 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
Psychiatric disorders Insomnia	7.3% 16/220 • Number of events 16 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	6.8% 15/222 • Number of events 16 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
Gastrointestinal disorders Nausea	7.3% 16/220 • Number of events 16 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	9.5% 21/222 • Number of events 23 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
Skin and subcutaneous tissue disorders Rash	5.9% 13/220 • Number of events 13 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	7.7% 17/222 • Number of events 22 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
Investigations Weight gain	5.9% 13/220 • Number of events 13 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	4.5% 10/222 • Number of events 10 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
Gastrointestinal disorders Constipation	2.7% 6/220 • Number of events 7 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	6.3% 14/222 • Number of events 14 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
Infections and infestations Oral Candiasis	1.8% 4/220 • Number of events 5 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	6.8% 15/222 • Number of events 15 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
Metabolism and nutrition disorders Vitamin D deficiency	3.2% 7/220 • Number of events 7 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	5.4% 12/222 • Number of events 12 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.
Gastrointestinal disorders Vomiting	2.3% 5/220 • Number of events 5 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.	6.8% 15/222 • Number of events 15 • The AE reporting period was from consent until the subject's final study visit (Week 52). In addition, any untoward event that may occur subsequent to the reporting period that the Investigator assessed as possibly, probably or definitely related to the study drug medication was reported as an AE.