Trial Outcomes & Findings for A Trial With TMC278-TIDP6-C222 for Continued TMC278 Access in Patients Infected With Human Immunodeficiency Virus-1 (NCT NCT01266902)

Last Updated: 2021-03-04

Results Overview

An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

482 participants

Primary outcome timeframe

Up to 7 years

Results posted on

2021-03-04

Participant Flow

Total of 482 participants were treated and 437 discontinued at data cut-off date (8 February 2018) because they switched to commercially available rilpivirine (RPV) (371 participants), as planned per protocol. Only 6 of the 482 participants discontinued as they reached a virologic endpoint. At last contact date of last participant under Protocol Amendment 3 (28 February 2020), out of 45 participants 37 switched to commercially available RPV and 6 were lost to follow-up.

Participant milestones

Participant milestones
Measure	Rilpivirine (RPV) (TMC278-C204 [C204]) Participants who rolled over from trial C204 (NCT00110305) continued to receive RPV 25 milligrams (mg) once daily (qd) in combination with an investigator-selected background regimen consisting of 2 nucleos(t)ide reverse transcriptase inhibitors (N\[t\]RTI)s starting Day 1.	RPV (TMC278-TiDP6-C209 [C209] and TMC278-TiDP6-C215 [C215]) Participants who rolled over from trial C209 (NCT00540449) and C215 (NCT00543725) continued to receive RPV 25 mg qd in combination with an investigator-selected background regimen consisting of 2 N(t)RTIs starting Day 1. In trial C209, the background regimen was fixed to tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) and in trial C215, the background regimen was selected by the investigator and contained either abacavir (ABC)/lamivudine (3TC), zidovudine (AZT)/3TC, or TDF/FTC.	RPV 25 mg (After Protocol Amendment 3) All Participants who were continued under a simplified study setting with only a minimum of study-related activities, as per Protocol Amendment 3 continued to receive RPV 25 mg and followed up for safety.
Period 1 (Main Study) STARTED	119	363	0
Period 1 (Main Study) COMPLETED	89	282	0
Period 1 (Main Study) NOT COMPLETED	30	81	0
Period 2 (After Protocol Amendment 3) STARTED	0	0	45
Period 2 (After Protocol Amendment 3) COMPLETED	0	0	37
Period 2 (After Protocol Amendment 3) NOT COMPLETED	0	0	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Rilpivirine (RPV) (TMC278-C204 [C204]) Participants who rolled over from trial C204 (NCT00110305) continued to receive RPV 25 milligrams (mg) once daily (qd) in combination with an investigator-selected background regimen consisting of 2 nucleos(t)ide reverse transcriptase inhibitors (N\[t\]RTI)s starting Day 1.	RPV (TMC278-TiDP6-C209 [C209] and TMC278-TiDP6-C215 [C215]) Participants who rolled over from trial C209 (NCT00540449) and C215 (NCT00543725) continued to receive RPV 25 mg qd in combination with an investigator-selected background regimen consisting of 2 N(t)RTIs starting Day 1. In trial C209, the background regimen was fixed to tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) and in trial C215, the background regimen was selected by the investigator and contained either abacavir (ABC)/lamivudine (3TC), zidovudine (AZT)/3TC, or TDF/FTC.	RPV 25 mg (After Protocol Amendment 3) All Participants who were continued under a simplified study setting with only a minimum of study-related activities, as per Protocol Amendment 3 continued to receive RPV 25 mg and followed up for safety.
Period 1 (Main Study) Investigator's decision/Participant's decision	2	3	0
Period 1 (Main Study) Lost to Follow-up	5	12	0
Period 1 (Main Study) Lack of Efficacy	4	2	0
Period 1 (Main Study) Adverse Event	3	11	0
Period 1 (Main Study) Withdrawal by Subject	2	12	0
Period 1 (Main Study) Subject non-compliant	3	7	0
Period 1 (Main Study) Continued RPV treatment	11	34	0
Period 2 (After Protocol Amendment 3) Withdrawal by Subject	0	0	1
Period 2 (After Protocol Amendment 3) Adverse Event	0	0	1
Period 2 (After Protocol Amendment 3) Lost to Follow-up	0	0	6

Baseline Characteristics

A Trial With TMC278-TIDP6-C222 for Continued TMC278 Access in Patients Infected With Human Immunodeficiency Virus-1

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rilpivirine (RPV) (TMC278-C204 [C204]) n=119 Participants Participants who rolled over from trial C204 (NCT00110305) continued to receive RPV 25 milligrams (mg) once daily (qd) in combination with an investigator-selected background regimen consisting of 2 nucleos(t)ide reverse transcriptase inhibitors (N\[t\]RTI)s starting Day 1.	RPV (TMC278-TiDP6-C209 [C209] and TMC278-TiDP6-C215 [C215]) n=363 Participants Participants who rolled over from trial C209 (NCT00540449) and C215 (NCT00543725) continued to receive RPV 25 mg qd in combination with an investigator-selected background regimen consisting of 2 N(t)RTIs starting Day 1. In trial C209, the background regimen was fixed to tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) and in trial C215, the background regimen was selected by the investigator and contained either abacavir (ABC)/lamivudine (3TC), zidovudine (AZT)/3TC, or TDF/FTC.	Total n=482 Participants Total of all reporting groups
Age, Continuous	42 years STANDARD_DEVIATION 8.18 • n=5 Participants	39.9 years STANDARD_DEVIATION 9.09 • n=7 Participants	40.4 years STANDARD_DEVIATION 8.91 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	84 Participants n=7 Participants	125 Participants n=5 Participants
Sex: Female, Male Male	78 Participants n=5 Participants	279 Participants n=7 Participants	357 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Asian	43 participants n=5 Participants	58 participants n=7 Participants	101 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	17 participants n=5 Participants	64 participants n=7 Participants	81 participants n=5 Participants
Race/Ethnicity, Customized Other	9 participants n=5 Participants	0 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized White	50 participants n=5 Participants	237 participants n=7 Participants	287 participants n=5 Participants
Region of Enrollment ARGENTINA	19 participants n=5 Participants	16 participants n=7 Participants	35 participants n=5 Participants
Region of Enrollment AUSTRALIA	0 participants n=5 Participants	11 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment AUSTRIA	2 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment BELGIUM	0 participants n=5 Participants	13 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment CANADA	0 participants n=5 Participants	21 participants n=7 Participants	21 participants n=5 Participants
Region of Enrollment CHILE	0 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment CHINA	8 participants n=5 Participants	18 participants n=7 Participants	26 participants n=5 Participants
Region of Enrollment DENMARK	0 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment FRANCE	5 participants n=5 Participants	15 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment GERMANY	3 participants n=5 Participants	24 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment ITALY	0 participants n=5 Participants	10 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment NETHERLANDS	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment PUERTO RICO	7 participants n=5 Participants	0 participants n=7 Participants	7 participants n=5 Participants
Region of Enrollment ROMANIA	0 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment RUSSIAN FEDERATION	11 participants n=5 Participants	27 participants n=7 Participants	38 participants n=5 Participants
Region of Enrollment SOUTH AFRICA	13 participants n=5 Participants	35 participants n=7 Participants	48 participants n=5 Participants
Region of Enrollment SPAIN	0 participants n=5 Participants	14 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment SWEDEN	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment TAIWAN	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment THAILAND	34 participants n=5 Participants	31 participants n=7 Participants	65 participants n=5 Participants
Region of Enrollment UNITED KINGDOM	8 participants n=5 Participants	17 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment UNITED STATES	9 participants n=5 Participants	76 participants n=7 Participants	85 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 7 years

Population: The intent-to-treat (ITT) population included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimens.

Outcome measures

Outcome measures
Measure	Rilpivirine (RPV) (TMC278-C204 [C204]) n=119 Participants Participants that rolled over from trial C204 (NCT00110305) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1.	RPV (TMC278-TiDP6-C209 [C209] and TMC278-TiDP6-C215 [C215]) n=363 Participants Participants that rolled over from trial C209 (NCT00540449) and C215 (NCT00543725) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1. In trial C209, the background regimen was fixed to TDF/FTC and in trial C215, the background regimen was selected by the investigator and contained either ABC/3TC, AZT/3TC, or TDF/FTC.
Number of Participants With Adverse Events (AEs)	32 Participants	70 Participants

PRIMARY outcome

Timeframe: Up to 7 years

Population: The ITT population included all participants who have taken at least 1 dose of RPV, regardless of their compliance with the protocol and adherence to the dosing regimens.

Number of participants with grade 3/4 events of rash irrespective of causality were assessed. A grade 3 rash defined as diffuse macular, maculopapular or morbilliform rash with vesicles or limited number of bullae or; rash with superficial ulcerations of mucous membranes limited to 1 anatomical site or; rash with at least one of the following: elevations in aspartate aminotransferase (AST)/alanine aminotransferase (ALT) more than 2\*baseline value and at least 5 times upper limit of normal; fever greater than (\>) 38 degree celsius or 100 degree fahrenheit; eosinophils \> 1000/millimeter (mm)\^3; serum sickness-like reaction. A grade 4 rash defined as the following: extensive or generalized bullous lesions or; Stevens-Johnsons Syndrome (SJS) or ulceration of mucous membrane involving 2 or more distinct mucosal sites or toxic epidermal necrolysis.

Outcome measures

Outcome measures
Measure	Rilpivirine (RPV) (TMC278-C204 [C204]) n=119 Participants Participants that rolled over from trial C204 (NCT00110305) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1.	RPV (TMC278-TiDP6-C209 [C209] and TMC278-TiDP6-C215 [C215]) n=363 Participants Participants that rolled over from trial C209 (NCT00540449) and C215 (NCT00543725) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1. In trial C209, the background regimen was fixed to TDF/FTC and in trial C215, the background regimen was selected by the investigator and contained either ABC/3TC, AZT/3TC, or TDF/FTC.
Number of Participants With Grade 3/4 Events of Rash Irrespective of Causality	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 360

Population: The ITT population included all participants who have taken at least 1 dose of RPV, regardless of their compliance with the protocol and adherence to the dosing regimens.

Time to virologic rebound was time to (first) human immunodeficiency virus type1 (HIV-1) ribonucleic acid (RNA) greater than or equal to (\>=) 50 or \>=200 copies/milliliter (copies/mL). The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.

Outcome measures

Outcome measures
Measure	Rilpivirine (RPV) (TMC278-C204 [C204]) n=119 Participants Participants that rolled over from trial C204 (NCT00110305) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1.	RPV (TMC278-TiDP6-C209 [C209] and TMC278-TiDP6-C215 [C215]) n=363 Participants Participants that rolled over from trial C209 (NCT00540449) and C215 (NCT00543725) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1. In trial C209, the background regimen was fixed to TDF/FTC and in trial C215, the background regimen was selected by the investigator and contained either ABC/3TC, AZT/3TC, or TDF/FTC.
Time to Virologic Rebound >= 200 copies/mL	1901.3 days Standard Error 47.19	1877.3 days Standard Error 25.93
Time to Virologic Rebound >= 50 copies/mL	1670.6 days Standard Error 51.32	1939.3 days Standard Error 52.43

SECONDARY outcome

Timeframe: Up to Week 360

Population: The ITT population included all participants who have taken at least 1 dose of RPV, regardless of their compliance with the protocol and adherence to the dosing regimen.

Time to treatment failure was defined as time to virologic rebound (time to first HIV-1 RNA \>= 50 or \>= 200 copies/mL) or discontinuation for reason other than RPV having become commercially available in the participating country, whichever came first, calculated as the time (in days) from baseline until treatment failure. The mean survival time and its standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.

Outcome measures

Outcome measures
Measure	Rilpivirine (RPV) (TMC278-C204 [C204]) n=119 Participants Participants that rolled over from trial C204 (NCT00110305) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1.	RPV (TMC278-TiDP6-C209 [C209] and TMC278-TiDP6-C215 [C215]) n=363 Participants Participants that rolled over from trial C209 (NCT00540449) and C215 (NCT00543725) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1. In trial C209, the background regimen was fixed to TDF/FTC and in trial C215, the background regimen was selected by the investigator and contained either ABC/3TC, AZT/3TC, or TDF/FTC.
Time To Treatment Failure >= 50 copies/mL	1795.7 days Standard Error 70.03	1694.1 days Standard Error 59.42
Time To Treatment Failure >= 200 copies/mL	1868.7 days Standard Error 63.29	1637.5 days Standard Error 42.42

SECONDARY outcome

Timeframe: Baseline up to weeks 96, 192, 288, 336

Population: The ITT population included all participants who have taken at least 1 dose of RPV, regardless of their compliance with the protocol and adherence to the dosing regimen. Here 'number of participants analyzed' signifies number of participants analyzed in this outcome measure. Here 'number analyzed' included all participants evaluable at specified timepoint categories.

The immunologic assessment was determined by change from baseline in CD4+ cell count for observed case approach.

Outcome measures

Outcome measures
Measure	Rilpivirine (RPV) (TMC278-C204 [C204]) n=119 Participants Participants that rolled over from trial C204 (NCT00110305) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1.	RPV (TMC278-TiDP6-C209 [C209] and TMC278-TiDP6-C215 [C215]) n=363 Participants Participants that rolled over from trial C209 (NCT00540449) and C215 (NCT00543725) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1. In trial C209, the background regimen was fixed to TDF/FTC and in trial C215, the background regimen was selected by the investigator and contained either ABC/3TC, AZT/3TC, or TDF/FTC.
Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count for Observed Case Approach Until Week 336 Week 96	72.63 cells/microliter (cells/mcL) Standard Error 20.581	55.91 cells/microliter (cells/mcL) Standard Error 13.425
Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count for Observed Case Approach Until Week 336 Week 192	148.76 cells/microliter (cells/mcL) Standard Error 24.111	132.73 cells/microliter (cells/mcL) Standard Error 21.989
Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count for Observed Case Approach Until Week 336 Week 288	122.29 cells/microliter (cells/mcL) Standard Error 29.628	101.50 cells/microliter (cells/mcL) Standard Error 24.108
Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count for Observed Case Approach Until Week 336 Week 336	161.73 cells/microliter (cells/mcL) Standard Error 39.851	76.49 cells/microliter (cells/mcL) Standard Error 40.484

SECONDARY outcome

Timeframe: Baseline up to weeks 96, 192, 288, 336

Change from baseline in CD4+ cell count were reported for NC=F approach (participants who discontinued because RPV became commercially available or could be accessed through another source or because the participants switched to other local \[RPV-based\] treatment options or local standard of care, were censored at that time; other participants after discontinuation had their CD4+ values imputed with baseline value. Intermittently missing values were imputed with a last observation carried-forward approach).

Outcome measures

Outcome measures
Measure	Rilpivirine (RPV) (TMC278-C204 [C204]) n=119 Participants Participants that rolled over from trial C204 (NCT00110305) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1.	RPV (TMC278-TiDP6-C209 [C209] and TMC278-TiDP6-C215 [C215]) n=363 Participants Participants that rolled over from trial C209 (NCT00540449) and C215 (NCT00543725) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1. In trial C209, the background regimen was fixed to TDF/FTC and in trial C215, the background regimen was selected by the investigator and contained either ABC/3TC, AZT/3TC, or TDF/FTC.
Change From Baseline in CD4+ Cell Count for Non-Completer Equals Failure (NC=F) Approach Until Week 336 Week 192	133.56 cells/mcL Standard Error 21.906	91.69 cells/mcL Standard Error 15.563
Change From Baseline in CD4+ Cell Count for Non-Completer Equals Failure (NC=F) Approach Until Week 336 Week 288	92.12 cells/mcL Standard Error 22.809	63.33 cells/mcL Standard Error 17.132
Change From Baseline in CD4+ Cell Count for Non-Completer Equals Failure (NC=F) Approach Until Week 336 Week 96	69.76 cells/mcL Standard Error 19.372	42.19 cells/mcL Standard Error 11.525
Change From Baseline in CD4+ Cell Count for Non-Completer Equals Failure (NC=F) Approach Until Week 336 Week 336	70.69 cells/mcL Standard Error 23.558	49.24 cells/mcL Standard Error 16.688

SECONDARY outcome

Timeframe: Up to 7 years

Population: The ITT population included all participants who have taken at least 1 dose of RPV, regardless of their compliance with the protocol and adherence to the dosing regimens.

A SAE is any untoward medical occurrence that at any dose: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	Rilpivirine (RPV) (TMC278-C204 [C204]) n=119 Participants Participants that rolled over from trial C204 (NCT00110305) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1.	RPV (TMC278-TiDP6-C209 [C209] and TMC278-TiDP6-C215 [C215]) n=363 Participants Participants that rolled over from trial C209 (NCT00540449) and C215 (NCT00543725) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1. In trial C209, the background regimen was fixed to TDF/FTC and in trial C215, the background regimen was selected by the investigator and contained either ABC/3TC, AZT/3TC, or TDF/FTC.
Number of Participants With Serious Adverse Events (SAEs)	9 Participants	14 Participants

SECONDARY outcome

Timeframe: Up to 7 years

Population: The ITT population included all participants who have taken at least 1 dose of RPV, regardless of their compliance with the protocol and adherence to the dosing regimens.

Number of participants with AEs related to RPV were assessed. An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non investigational) product.

Outcome measures

Outcome measures
Measure	Rilpivirine (RPV) (TMC278-C204 [C204]) n=119 Participants Participants that rolled over from trial C204 (NCT00110305) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1.	RPV (TMC278-TiDP6-C209 [C209] and TMC278-TiDP6-C215 [C215]) n=363 Participants Participants that rolled over from trial C209 (NCT00540449) and C215 (NCT00543725) continued to receive RPV 25 mg qd in combination with a background regimen consisting of 2 N(t)RTIs starting Day 1. In trial C209, the background regimen was fixed to TDF/FTC and in trial C215, the background regimen was selected by the investigator and contained either ABC/3TC, AZT/3TC, or TDF/FTC.
Number of Participants With AEs Related to Rilpivirine (RPV)	7 Participants	16 Participants

Adverse Events

Rilpivirine (RPV) (TMC278-C204 [C204])

Serious events: 9 serious events

Other events: 25 other events

Deaths: 0 deaths

RPV (TMC278-TiDP6-C209 [C209] and TMC278-TiDP6-C215 [C215])

Serious events: 16 serious events

Other events: 61 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Director

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	Rilpivirine (RPV) (TMC278-C204 [C204]) n=119 participants at risk Participants who rolled over from trial C204 (NCT00110305) continued to receive RPV 25 milligrams (mg) once daily (qd) in combination with an investigator-selected background regimen consisting of 2 nucleos(t)ide reverse transcriptase inhibitors (N\[t\]RTI)s starting Day 1.	RPV (TMC278-TiDP6-C209 [C209] and TMC278-TiDP6-C215 [C215]) n=363 participants at risk Participants who rolled over from trial C209 (NCT00540449) and C215 (NCT00543725) continued to receive RPV 25 mg qd in combination with an investigator-selected background regimen consisting of 2 N(t)RTIs starting Day 1. In trial C209, the background regimen was fixed to tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) and in trial C215, the background regimen was selected by the investigator and contained either abacavir (ABC)/lamivudine (3TC), zidovudine (AZT)/3TC, or TDF/FTC.
Blood and lymphatic system disorders Haemolytic anaemia	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Cardiac disorders Cardiac hypertrophy	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Cardiac disorders Coronary artery disease	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Gastrointestinal disorders Abdominal discomfort	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Gastrointestinal disorders Abdominal pain	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
General disorders Chest pain	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
General disorders Death	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Hepatobiliary disorders Cholelithiasis	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Infections and infestations Bronchitis	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Infections and infestations Dengue fever	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Infections and infestations Liver abscess	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Infections and infestations Lung infection	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Infections and infestations Pneumonia	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Infections and infestations Syphilis	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Injury, poisoning and procedural complications Foot fracture	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Injury, poisoning and procedural complications Hand fracture	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Injury, poisoning and procedural complications Limb injury	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Injury, poisoning and procedural complications Stab wound	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Investigations Blood glucose increased	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal adenoma	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Nervous system disorders Cerebrovascular accident	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Nervous system disorders Ischaemic stroke	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Nervous system disorders Sciatica	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.55% 2/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Psychiatric disorders Anxiety	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Renal and urinary disorders Renal failure	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.84% 1/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.00% 0/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Vascular disorders Thrombophlebitis	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.
Vascular disorders Varicose vein	0.00% 0/119 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.	0.28% 1/363 • Up to 7 years Safety analysis included all participants who have taken at least 1 dose of rilpivirine (RPV), regardless of their compliance with the protocol and adherence to the dosing regimen.