Trial

(ClinicalTrials.gov reference number)

Reference(s)

Type of Clinical Trial

Study Period

Geographic Area

No. (Treated: Control) and Type (naïve/virologically suppressed) of Enrolled Patients

Patient Characteristics at Baseline:

- age (mean/median)

- time since treatment started (for treatment-experienced patients)

- cut-off for plasma viral load (copies/ml)

- cut-off for CD4 cell count (μL)

Duration of Follow-Up (weeks)

RPV Regimen Group

Control Group Regimen

Treatment -naïve patients

TMC278-C204

NCT00110305 Pozniak 2010 [33] (week 48 and 96 results)

Wilkin 2012 [6] (week 192 results)

Phase 2b

randomized

open label^*

dose-finding

multicenter

trial

2005-2011

14 countries (USA, Russia, Puerto Rico, South Africa, Uganda, 4 countries in Europe, 3 in Latin America, and 2 in Asia)

93^◊:89

Treatment-naïve

^◊All RPV doses: 279

(not considered: RPV 75 mg: n = 95

RPV 150 mg: n = 91)

- 36 y (median age) in the 25 mg/day RPV arm (35 y all patients)

- pVL > 5000

- CD4 not limited

4-week screening period

96-week treatment

4-week follow-up

RPV (25 mg^◊◊) + one of the following regimens:

TDF/FTC

AZT/3TC

^◊◊3 RPV arms: 25/75/150 mg/day)

EFV (600 mg/day) + one of the following regimens:

TDF/FTC

AZT/3TC

ECHO

NCT00540449

Molina 2011 [3] (week 48 results)

Pooled analysis with THRIVE^§: Cohen 2012 [36]

(week 48 results)

Cohen 2013 [5] (week 96 results)

Phase 3

randomized

double-blind

noninferiority

trial

2008-2011

21 countries (USA, Canada Australia, South Africa, 10 countries in Europe, 3 in Asia, and 4 in Latina America)

346:344

Treatment-naïve

- 36 y (median age) in the RPV group and 36 in the control group

- pVL ≥ 5000

- CD4 not limited

6-week screening period

96-week treatment

4-week follow-up

RPV (25 mg/day) + TDF/FTC

EFV (600 mg/day) +

TDF/FTC

THRIVE

NCT00543725 Cohen 2011 [4]

(week 48 results)

Pooled analysis with THRIVE^§: Cohen 2012 [36]

(week 48 results)

Cohen 2013 [5] (week 96 results)

Phase 3

randomized

double-blind

noninferiority

multicenter

trial

2008-2011

21 countries (USA, Puerto Rico, Canada Australia, South Africa, 7 countries in Europe, 4 in Asia, and 6 in Latina America)

340:338

Treatment-naïve

- 36 y (median age) in the RPV group and 36 in the control group

- pVL ≥ 5000

- CD4 not limited

6-week screening period

96-week treatment

4-week follow-up

RPV (25 mg/day) + one of the following regimens:

TDF/FTC

AZT/3TC

ABC/3TC

EFV (600 mg/day) + one of the following regimens:

TDF/FTC

AZT/3TC

ABC/3TC

STAR

GS-US-264-0110

NCT01309243 Cohen 2014 [32] (week 48 results)

Van Lunzen [7] 2016 (week 96 results)

Phase 3b

randomized

open-label

noninferiority

multicenter

trial

2011-2013

12 countries (USA, Canada, Australia, Puerto Rico and

8 countries in Europe)

394:392

Treatment-naïve

- 37 y (median age) in the RPV group and 35 in the control group

- pVL > 2500

- CD4 not limited

96-week treatment

RPV (25 mg/day) + FTC/TDF

(single tablet)

EFV (600 mg/day)

/FTC/TDF

(single tablet)

Treatment-experienced, virologically controlled patients

SPIRIT

GS-US-264-0106

NCT01252940

Palella 2014 [10]

Phase 3b

randomized

open-label

noninferiority

multicenter

trial

2010-2012

Europe and USA (9 countries)

317:159°

virologically suppressed

(for ≥ 6 months)

°317:152 in the late switch phase

- 42 y (median age) in the immediate switch arm and 43 y in the delayed switch arm

- median time since first ART 2.9 y in the immediate switch arm and 2.6 y in the delayed switch arm

- pVL < 50

48-week treatment

(immediate switch arm)

RPV (25 mg/day) + FTC/TDF

(delayed switch arm)

Day 1-week 24: ongoing PI + RTV + 2NRTIs

week 24-48:

RPV (25 mg/day) + FTC/TDF

LATTE

NCT01641809

Margolis 2015 [28]

Phase 2b

randomized

open label^**

multicenter

trial

2012-2018

USA and Canada

Induction phase:

181^:62

Treatment-naïve

Maintenance phase:

160^*:47

virologically suppressed by week 24 in the induction phase

^*RPV + CAB 10 mg:

n = 52

RPV + CAB 30 mg:

n = 53

RPV + CAB 60 mg:

n = 55

Induction phase:

- 32.5 y (median) in the induction phase and 33.0 y in the maintenance phase

- pVL ≥ 1000 (at start of induction phase); in the maintenance phase: patients who had received CAB in the induction phase and were virologically suppressed at week 24 and patients who had received EFV in the induction phase with a week 24 visit irrespective pVL.

- CD4 ≥ 200

Induction phase:

24-week treatment

Maintenance phase:

72-week treatment

Induction phase:

CAB (10 mg/30 mg/60 mg/day) + one of the following regimens:

- TDF/FTC

- ABC/3TC

Maintenance phase:

RPV (25 mg/day) + CAB (10 mg/30 mg/60 mg/day)

Induction phase:

EFV (600 mg/day) + 2 NRTIs:

- TDF/FTC

- ABC/3TC

Maintenance phase:

EFV (600 mg/day) + one of the following regimens:

- TDF/FTC

- ABC/3TC

Probe

Maggiolo 2016 [11]

Phase 4

randomized

open-label

proof-of-concept

noninferiority

single center

trial

2014

Italy

30:30

virologically suppressed

(on PI + RTV + 2NRTIs for ≥ 6 months)

- 49 y (mean age) in the switch arm and 48 y in the continuation arm

- mean cART duration 93 months in the switch arm and 98 months in the continuation arm

- pVL < 50

- CD4 not limited

48-week treatment

(switch arm)

RPV (25 mg/day) + DRV/RTV

(continuation arm)

Ongoing cART 2NRTIs + PI

GS-US-366-1160

NCT02345226 DeJesus 2017 [34] (week 48 results)

Hagins 2018 [12] (week 96 results)

Phase 3b

randomized

double-blind

noninferiority multicenter

trial

2015-2019

USA, Canada, and 6 countries in Europe

438:437

virologically suppressed (on EFV/FTC/TDF for ≥ 6 months)

- 49 y (median age) in the switch arm and 48 y in the continuation arm

- median duration of baseline ART 6.5 y in the switch arm and 6.6 in the continuation arm

- pVL < 50

- CD4 not limited

96-week treatment

(switch arm)

RPV (25 mg/day) + FTC/TAF

(single tablet)

(continuation arm)

EFV/FTC/TDF

(single tablet)

SWORD-1

NCT02429791

SWORD-2

NCT02422797 Llibre 2018 [9] (week 48 results)

Aboud 2019 [8] (week 100 results)

Aboud 2019 [8] (week 148 results)

Phase 3

randomized

open-label

noninferiority

multicenter

trials

2015-

ongoing

12 countries

(USA, Canada, Argentina, Taiwan, Russian Federation and 7 countries in Europe)

513:511^$

virologically suppressed

(for at least 6 months before enrollment)

^$513:477 in the late switch phase

- 43 y (median age) in both the switch arm and the continuation arm

- median ART duration 51 months in the switch arm and 53 months in the continuation arm

- pVL < 50

- CD4 not limited

148-week treatment

day 1- week 52:

early switch phase

week 52-148: late switch phase

(immediate switch arm)

RPV (25 mg/day) + DTG

(delayed switch arm)

day 1-week 52: ongoing 3-drug ART

Week 52-148: RPV (25 mg/day) + DTG

SALIF

Munderi 2019 [13]

Phase 3b

randomized

open-label

noninferiority

multicenter

trial

2013-2015

Cameroon, Kenya, Senegal, South Africa

213:211

virologically suppressed

(on first line NNRTI-based [EFV or NVP] ART)

- 40.6 y (median age)

- median ART duration 5.2 y

- pVL < 50

- CD4 > 200

48-108 week treatment

RPV (25 mg/day) + FTC/TDF

TDF/FTC/EFV

NCT03664440 Petchkum 2019 [14]

Randomized

noninferiority

single-center

trial

2016-2017

Thailand

51:55

virologically suppressed (on NVP-based ART for ≥ 6 months)

- 48 y (mean age) in the switch arm and 50 y in the continuation arm

- mean ART duration 10.8 y in the switch arm and 11.0 y in the continuation arm

- pVL < 40

- CD4 not limited

48-week treatment

(switch arm)

RPV (25 mg/day) + one of the following regimens:

- TDF/3TC

- TDF/FTC

(continuation arm)

NPV (200 mg twice/day) + one of the following regimens:

- TDF/3TC

- TDF/FTC