Rilpivirine-Tenofovir DF-Emtricitabine ( Complera ) David H. Spach, - - PowerPoint PPT Presentation

Rilpivirine-Tenofovir DF-Emtricitabine (Complera)

David H. Spach, MD Brian R. Wood, MD

Last Updated: December 20, 2019

Rilpivirine-Emtricitabine-Tenofovir DF (Complera)

Image Source: AIDS Info.org

Rilpivirine-Tenofovir DF-Emtricitabine

NRTI NRTI NNRTI

Complera

[kom-PLEH-rah]

25 mg 300 mg 200 mg Dose: 1 tablet once daily with food

Rilpivirine-Tenofovir DF-Emtricitabine (Complera)

• Complera Components:

Rilpivirine 25 mg Tenofovir disoproxil fumarate (DF): 300 mg Emtricitabine: 200 mg

• Dosing: 1 tablet once daily with food
• Common Adverse Events (≥2%)
• Depression, insomnia, headache

• Phase 3 Trials in Treatment Naïve
• ECHO: RPV + TDF-FTC versus EFV + TDF-FTC
• THRIVE: RPV + 2NRTIs versus EFV + 2NRTIs
• STaR: RPV-TDF-FTC versus EFV-TDF-FTC
• Switch/Simplification Trials
• GS-264-0111: EFV-TDF-FTC versus RPV-TDF-FTC
• SPIRIT: Switch to RPV-TDF-FTC from ritonavir-boosted PI + 2NRTIs
• Near Rwanda: Switch to RPV-TDF-FTC from NVP-based regimen
• HIV-HCV Coinfection
• hEPAtic: Hepatic safety of RPV-TDF-FTC in HIV-HCV Coinfection
• Nonoccupational PEP
• EPEP: RPV-TDF-FTC for nonoccupational PEP in MSM

Rilpivirine-Tenofovir DF-Emtricitabine Summary of Key Studies

Rilpivirine-Tenofovir DF-Emtricitabine

INITIAL THERAPY

Rilpivirine + TDF-FTC versus Efavirenz + TDF-FTC

ECHO Trial

Rilpivirine + TDF-FTC versus Efavirenz + TDF-FTC

ECHO: Study Design

Source: Molina J-M, et al. Lancet. 2011;378:238-46.

Rilpivirine + TDF-FTC QD

(n = 346)

Efavirenz + TDF-FTC QD

(n = 344)

Study Design: ECHO Study

• Background: Randomized, double-blind, phase 3

trial comparing rilpivirine and efavirenz in combination with a fixed background regimen consisting of tenofovir DF-emtricitabine in treatment-naïve adult with HIV

• Inclusion Criteria (n = 690)
• Antiretroviral-naïve adults
• Age >18 years
• HIV RNA ≥5000 copies/mL
• No resistance to any study drugs
• Treatment Arms
• Rilpivirine + Tenofovir DF-Emtricitabine
• Efavirenz + Tenofovir DF-Emtricitabine

Rilpivirine + TDF-FTC versus Efavirenz + TDF-FTC

ECHO: Result

48 Week Virologic Response ( ITT-TLOVR)

Source: Molina J-M, et al. Lancet. 2011;378:238-46. 83 90 79 62 83 83 83 81

20 40 60 80 100

All ≤100,000 100,000-500,000 >500,000

HIV RNA <50 copies/mL (%) Baseline HIV RNA (copies/mL)

Rilpivirine + TDF-FTC Efavirenz + TDF-FTC

287/346 285/344 162/181 136/163 104/131 111/134 21/34 38/47

Rilpivirine + TDF-FTC versus Efavirenz + TDF-FTC

ECHO: Result

48 Week Virologic Failure and Discontinuations (ITT-TLOVR)

Source: Molina J-M, et al. Lancet. 2011;378:238-46.

11 2 4 7 5 10 15 20 Virologic Failure Adverse Event Leading to Discontinuation

Participants (%) Rilpivirine + TDF-FTC Efavirenz + TDF-FTC

Rilpivirine + TDF-FTC versus Efavirenz + TDF-FTC

ECHO: Resistance Results

Incidence of NNRTI Resistance Associated Mutations (RAMs)

Source: Molina J-M, et al. Lancet. 2011;378:238-46.

20 40 60 80 100

E138K K101E Y181C V90I H221Y V189I E138Q K103N 69 19 19 15 15 12 8 88 Virologic Failure with NNRTI RAM (%)

Rilpivirine + TDF-FTC (n=26) Efavirenz + TDF-FTC (n=8)

Rilpivirine + TDF-FTC versus Efavirenz + TDF-FTC

ECHO: Resistance Results

Incidence of NNRTI Resistance Associated Mutations (RAMs)

Source: Molina J-M, et al. Lancet. 2011;378:238-46.

20 40 60 80 100

E138K K101E Y181C V90I H221Y V189I E138Q K103N 69 19 19 15 15 12 8 88 Virologic Failure with NNRTI RAM (%)

Rilpivirine + TDF-FTC (n=26) Efavirenz + TDF-FTC (n=8)

Rilpivirine + TDF-FTC versus Efavirenz + TDF-FTC

ECHO: Conclusions

Source: Molina J-M, et al. Lancet. 2011;378:238-46.

Interpretation: “Rilpivirine showed non-inferior efficacy compared with efavirenz, with a higher virological-failure rate, but a more favourable safety and tolerability profile.”

Rilpivirine-TDF-FTC versus Efavirenz-TDF-FTC

STaR Trial

Rilpivirine-TDF-FTC versus Efavirenz-TDF-FTC

STaR Study: Design

Source: Cohen C, et al. AIDS. 2014;28:989-97.

Rilpivirine-TDF-FTC QD

(n = 394)

Efavirenz-TDF-FTC QD

(n = 392)

Study Design: STaR Study

• Background: Randomized, open label, phase 3b

trial comparing safety and efficacy of two single- tablet regimens, RPV-TDF-FTC and EFV-TDF- FTC, in treatment-naïve adults with HIV

• Inclusion Criteria (n = 786)
• Antiretroviral-naïve adults
• Age >18 years
• HIV RNA ≥2500 copies/mL
• No resistance to EFV, RPV, TDF, or FTC
• Treatment Arms
• Rilpivirine-tenofovir DF-emtricitabine
• Efavirenz-tenofovir DF-emtricitabine

Rilpivirine-TDF-FTC versus Efavirenz-TDF-FTC

STaR: Result

Week 48 Virologic Response (Intent-to-Treat Analysis)

Source: Cohen C, et al. AIDS. 2014;28:989-97.

86 89 80 82 82 82

20 40 60 80 100

All ≤100,000 copies/mL >100,000 copies/mL HIV RNA <50 copies/mL (%) Baseline HIV RNA

RPV-TDF-FTC EFV-TDF-FTC

338/394 320/392 231/260 204/250 107/134 110/142

Rilpivirine-TDF-FTC versus Efavirenz-TDF-FTC

STaR: Result

48 Week Virologic Outcomes

Source: Cohen C, et al. AIDS. 2014;28:989-97.

86 8 6 82 6 13 20 40 60 80 100 Virologic Suppression Virologic Failure Missing Data

Patients (%) RPV-TDF-FTC EFV-TDF-FTC

Rilpivirine-TDF-FTC versus Efavirenz-TDF-FTC

STaR Study: Common Adverse Events

Source: Cohen C, et al. AIDS. 2014;28:989-97.

Treatment Emergent Adverse Events in > 5% of Subjects in Either Arm RPV-TDF-FTC

(n = 392)

EFV-TDF-FTC

(n = 394)

Dizziness 6.6% 22.2% Insomnia 9.6% 14.0% Somnolence 2.5% 6.9% Headache 12.4% 13.5% Abnormal Dreams 5.8% 24.5% Depression 6.6% 8.9% Anxiety 5.1% 8.4% Folliculitis 5.3% 1.0% Rash 6.1% 12.0%

RPV-FTC-TDF versus EFV-FTC-TDF

STaR Study: Conclusions from Primary Analysis

Source: Cohen C, et al. AIDS. 2014;28:989-97.

Conclusion: “In treatment-naive participants, RPV/FTC/TDF demonstrated noninferior efficacy and improved tolerability compared with EFV/FTC/TDF, as well as a statistically significant difference in efficacy for participants with baseline HIV-1 RNA 100,000 copies/ml or less at week 48.”

Rilpivirine-TDF-FTC versus Efavirenz-TDF-FTC

STaR Trial: Week 96 Resistance Data

Rilpivirine-TDF-FTC versus Efavirenz-TDF-FTC

STaR Study: Result

Development of Genotypic Resistance at Week 48

Source: Porter D, et al. J Acquir Immune Defic Syndr. 2014;65:318-26.

4.3 4.1 4.1 0.8 0.8 0.3

2 4 6 8 10

Resistance to study drugs Any NNRTI resistance Any NRTI resistance Patients (%)

RPV-TDF-FTC EFV-TDF-FTC

Rilpivirine-TDF-FTC versus Efavirenz-TDF-FTC

STaR Study: Result

Development of Resistance to Study Drugs at 48 weeks, by Viral Load

Source: Porter D, et al. J Acquir Immune Defic Syndr. 2014;65:318-26. .

4.3 1.9 9.0 0.8 0.8 0.7

2 4 6 8 10

All ≤100,000 copies/mL >100,000 copies/mL Patients (%) Baseline HIV RNA

RPV-TDF-FTC EFV-TDF-FTC

RPV-FTC-TDF versus EFV-FTC-TDF STaR Study: Conclusions from Resistance Analysis Population

Source: Porter D, et al. J Acquir Immune Defic Syndr. 2014;65:318-26.

Conclusions: “Among subjects in the primary resistance associated populations (RAP), resistance development to RPV/FTC/TDF consisted

• f NNRTI and NRTI mutations and was more frequent than resistance

development to EFV/FTC/TDF. In subjects with baseline viral load ≤ 100,000 copies/mL, resistance development was low (<2%) for both RPV/FTC/TDF and EFV/FTC/TDF arms and less frequent compared with subjects with baseline viral load >100,000 copies/mL, for RPV/FTC/TDF.”

Rilpivirine-Tenofovir DF-Emtricitabine

SWITCH STUDIES

Switch from EFV-TDF-FTC to RPV-TDF-FTC

GS-264-0111

Switch from EFV-TDF-FTC to RPV-TDF-FTC

GS-264-0111: Study Design

Source: Mills AM, et al. HIV Clin Trials. 2013;14:216-23.

Study Design: GS-264-0111 Study

• Background: Open-label, phase 2b study

evaluating the efficacy and safety of switching from EFV-TDF-FTC to RPV-TDF-FTC in virologically suppressed patients with HIV-1

• Inclusion Criteria (n = 49)
• Age ≥18 years
• On EFV-TDF-FTC for ≥3 months
• Experiencing efavirenz intolerance
• HIV RNA <50 copies/mL for ≥8 weeks
• No resistance to study drugs
• No proton pump inhibitor use
• CrCl ≥50 mL/min
• Switch Arm
• Rilpivirine-tenofovir DF-emtricitabine

RPV-TDF-FTC

(n = 49)

Week 48 Week 0 EFV-TDF-FTC

(n = 49)

Switch from EFV-TDF-FTC to RPV-TDF-FTC

GS-264-0111: Result

Virologic Outcomes at Weeks 12, 24, and 48

Source: Mills AM, et al. HIV Clin Trials. 2013;14:216-23.

100 100 94 20 40 60 80 100 12 Weeks 24 Weeks 48 Weeks HIV RNA <50 copies/mL (%)

Week Following Switch to RPV-TDF-FTC

49/49 49/49 46/49

Switch from EFV-TDF-FTC to RPV-TDF-FTC

GS-264-0111: Result

Week 24: Change in Plasma Lipids from Baseline

Source: Mills AM, et al. HIV Clin Trials. 2013;14:216-23.

• 17
• 8
• 2
• 26
• 40
• 30
• 20
• 10

Total Cholesterol LDL HDL Triglycerides

Change from baseline median (mg/dl)

Lipid Changes in Patients Switched to RPV-TDF-FTC

Switch from EFV-TDF-FTC to RPV-TDF-FTC

GS-264-0111: Conclusions

Source: Mills AM, et al. HIV Clin Trials. 2013;14:216-23.

Conclusions: “Switching from EFV/FTC/TDF to RPV/FTC/ TDF was a safe, efficacious option for virologically suppressed HIV-infected patients with efavirenz intolerance wishing to remain on an single tablet regimen.”

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

SPIRIT STUDY

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Study Design

Source: Palella FJ, et al. AIDS. 2014;28:335-44.

Immediate Switch Arm

RPV-TDF-FTC QD

(n = 317)

Delayed Switch Arm PI/r + 2 NRTIs x 24 weeks, then RPV-TDF-FTC QD

(n = 159)

Study Design: SPIRIT STUDY

• Background: Open label, randomized phase 3b

trial evaluating switching from ritonavir-boosted PI plus 2 NRTIs to single-tablet regimen of rilpivirine-tenofovir DF-emtricitabine once daily

• Inclusion Criteria (n = 476)
• Age >18 years
• HIV RNA <50 copies/mL for >6 months
• On PI/r >6 months
• No known resistance to study drugs
• Treatment Arms
• Rilpivirine-tenofovir DF-emtricitabine
• Ritonavir-boosted PI + 2 NRTIs x 24 weeks,

then rilpivirine-tenofovir DF-emtricitabine

1x 2x

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Study Design

Source: Palella FJ, et al. AIDS. 2014;28:335-44.

Baseline Antiretroviral Regimens Immediate Switch Arm

(n = 317)

Delayed Switch Arm

(n= 159)

NRTI at Screening TDF-FTC 80.4% 81.8% ABC-3TC 13.2% 13.2% Ritonavir-Boosted PI at Screening Atazanavir 38.5% 34.0% Lopinavir 30.6% 36.5% Darunavir 19.9% 20.8% Fosamprenavir 7.9% 7.5% Saquinavir 1.9% 1.3%

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Result

Week 24 Virologic Response (Intent-to-Treat Analysis)

Source: Palella FJ, et al. AIDS. 2014;28:335-44.

94 95 95 90 89 92 20 40 60 80 100 Overall ≤100,000 copies/mL >100,000 copies/mL HIV RNA <50 copies/mL (%)

Baseline HIV RNA Level RPV-FTC-TDF PI/r + 2NRTIs

297/317 143/159 155/163 83/93 125/131 48/52

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Result

Virologic Failure (HIV RNA ≥50 copies/mL) at Weeks 24 and 48

Source: Palella FJ, et al. AIDS. 2014;28:335-44.

0.9 2.5 5.0 1.3 2 4 6 8 24 Weeks 48 Weeks

Virologic Failure (%) Study Week Immediate switch Delayed switch

3/317 8/159 8/317 2/152

Week 24: Change in Plasma Lipids from Baseline

Source: Palella FJ, et al. AIDS. 2014;28:335-44.

• 25
• 16
• 53
• 6
• 1

3 1

• 80
• 60
• 40
• 20

20 Total Cholesterol LDL Triglycerides HDL

Mean change from baseline (mg/dl)

RPV-FTC-TDF PI/r + 2NRTIs

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Result

Week 48: Change in Plasma Lipids from Baseline

Source: Palella FJ, et al. AIDS. 2014;28(3):335-44.

• 24
• 16
• 64
• 2
• 24
• 14
• 80
• 4
• 100
• 80
• 60
• 40
• 20

Total Cholesterol LDL HDL Triglycerides

Mean change from baseline (mg/dl)

Immediate switch Delayed switch

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Result

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Result

Week 48 Virologic Outcomes in Patients with Resistance Mutations*

Source: Porter DP, et al. HIV Clin Trials. 2016;17:29-37.

83 6 11 20 40 60 80 100 Virologic Suppression Virologic Failure No Data in Window

Patients (%) RPV-FTC-TDF-treated patients

*Pre-existing NRTI or NNRTI resistance mutations by baseline proviral DNA or historical RNA genotype

29/35 2/35 4/35

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Conclusions

Source: Palella FJ, et al. AIDS. 2014;28:335-44.

Conclusion: “Switching to the STR RPV/FTC/TDF from an RTV- boosted protease inhibitor regimen in virologically suppressed, HIV-1- infected participants maintained virologic suppression with a low risk of virologic failure, while improving total cholesterol, LDL, and triglycerides.”

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Patient-Reported Outcomes

38 17 29 9 19 28 29 25 19 21 28 23 13 46 17 34 12 50 36 31 30 27 35 32 36 17

10 20 30 40 50 60

Fatigue Fever Memory Loss Nausea Diarrhea Sadness Anxiety Skin Problems Headache Bloating Muscle pain Sex problems Weight loss

Occurrence of HIV-Related Symptoms (%)

PI/r + 2NRTIs RPV-TDF-FTC

Source: Brunetta J, et al. Patient. 2015;8:257-67.

Switch to RPV-TDF-FTC from Ritonavir-boosted PI Regimen

Spirit: Conclusions

Source: Brunetta J, et al. Patient. 2015;8:257-67.

Conclusions: “These data suggest that switching to the STR RPV/FTC/TDF from a PI-based multi-pill regimen is associated with greater patient-reported treatment satisfaction and improved tolerability in HIV-1-infected, virologically suppressed individuals.”

Switch RPV-TDF-FTC from NVP-Based Regimen

NEAR-Rwanda Trial

Switch to RPV-TDF-FTC from NVP-Based Regimen

NEAR-Rwanda: Study Design

Source: Collins SE, et al. Open Forum Infect Dis. 2016;3:ofw141.

Switch Arm

RPV-TDF-FTC

(n = 99)

Continuation Arm

NVP + 2 NRTI’s

(n = 51)

Study Design: NEAR-Rwanda Study

• Background: Randomized, open-label, single-

center, non-inferiority study conducted in Rwanda to evaluate a switch from a NVP-based regimen to a single tablet regimen of RPV-TDF-FTC

• Inclusion Criteria (n = 150 enrolled)
• Rwandan adults with HIV-1 infection
• HIV RNA <50 copies/mL within 12 months of

screening and at screening visit

• On NVP + lamivudine + 2nd NRTI ≥12 months
• No prior virologic failure
• No prior ART change except NRTI substitution
• eGFR >60 mL/min and Hemoglobin >8 g/dL
• No active TB or pregnancy
• Treatment Arms (2:1 randomization)
• Continue NVP + 2 NRTI’s
• Switch to RPV-FTC-TDF

Switch to RPV-TDF-FTC from NVP-Based Regimen

NEAR-Rwanda: Results

24 Week Virologic Response (FDA Snapshot Analysis)

Source: Collins SE, et al. Open Forum Infect Dis. 2016;3:ofw141. 93 90 92 84

20 40 60 80 100

HIV RNA <200 copies/mL HIV RNA <50 copies/mL

Proportion at each endpoint (%)

Rilpivirine-Tenofovir DF-Emtricitabine Nevirapine + 2 NRTI's

92/99 47/51 89/99 43/51

Week 24: Change in Plasma Lipids from Baseline

Source: Collins SE, et al. Open Forum Infect Dis. 2016;3:ofw141.

• 16.6
• 2.8
• 9.2
• 12.0

0.0

• 0.1

2.5

• 30
• 20
• 10

10 20 Total Cholesterol LDL Triglycerides HDL

Mean change from baseline (mg/dL)

Rilpivirine-Tenofovir DF-Emtricitabine Nevirapine + 2 NRTI's

Switch to RPV-TDF-FTC from NVP-Based Regimen

NEAR-Rwanda: Results

Switch to RPV-TDF-FTC from NVP-Based Regimen

NEAR-Rwanda: Conclusions

Source: Collins SE, et al. Open Forum Infect Dis. 2016;3:ofw141.

Conclusions: “A switch from nevirapine-based ART to rilpivirine- emtricitabine-tenofovir disoproxil fumarate had similar virologic efficacy to continued nevirapine-based ART after 24 weeks with few adverse events.”

Rilpivirine-Tenofovir DF-Emtricitabine

HIV-HCV COINFECTION

Rilpivirine-TDF-FTC in HIV-HCV Coinfected Patients

hEPAtic Study

Rilpivirine-TDF-FTC in HIV-HCV Coinfected Patients

hEPAtic: Design

Source: Neukam K, et al. PLoS One. 2016;11:e0155842.

EPA group

RPV-TDF-FTC

(n = 173)

Control Group

Other ART Regimen

(n = 346)

Study Design: hEPAtic STUDY

• Background: Retrospective, case-control study to

evaluate the hepatic safety (as measured by frequency of transaminase and total bilirubin elevations) of rilpivirine-tenofovir DF-emtricitabine

• nce daily in HIV-HCV-coinfected patients.
• Inclusion Criteria (n = 519)
• Age >18 years
• Chronic HCV (detectable HCV RNA)
• Starting new antiretroviral (ART) regimen
• Treatment Arms
• EPA Group: Rilpivirine-tenofovir DF-emtricitabine
• Control Group: Other new antiretroviral regimen

2x 1x

EPA = rilpivirine-tenofovir DF-emtricitabine (Complera)

Rilpivirine-TDF-FTC in HIV-HCV-Coinfected Patients

hEPAtic: Patient characteristics

Source: Neukam K, et al. PLoS One. 2016;11:e0155842.

Newly introduced antiretroviral therapy (ART) in the control group (n=346) Antiretroviral Drug Initiated ART (%) Antiretroviral Drug Initiated ART (%) Tenofovir DF-emtricitabine 21.7 Efavirenz 9.5 Abacavir-lamivudine 12.4 Nevirapine 2.9 Other NRTI combinations 11 Etravirine 8.7 Lopinavir/ritonavir 4.3 Raltegravir 13 Atazanavir/ritonavir 13.9 Maraviroc 6.9 Darunavir/ritonavir 32.9

Rilpivirine-TDF-FTC in HIV-HCV-Coinfected Patients

hEPAtic: Result

Frequency of Severe Hepatic Toxicity

Source: Neukam K, et al. PLoS One. 2016;11:e0155842.

1.2 0.6 3.2 2.3

1 2 3 4 Grade 3-4 Transaminase Elevations (TE) Grade 4 Total Bilirubin Elevations (TBE)

Patients (%) Marker of Severe Hepatic Toxicity

RPV-TDF-FTC Control group

2/173 11/346 1/173 8/346

Grade 3 TE = ALT or AST 5-10x ULN; Grade 4 TE = ALT or AST > 10x ULN; Grade 4 TBE: total bilirubin ≥ 5 mg/dL

Rilpivirine-TDF-FTC in HIV-HCV-Coinfected Patients

hEPAtic: Result

Discontinuation, Decompensation, and Death

Source: Neukam K, et al. PLoS One. 2016;11:e0155842.

8.0 0.6 1 5.2 1.7 0.2

2 4 6 8 10

Discontinuation for any Adverse Event Hepatic Decompensation Death due to Hepatic Event Patients (%)

RPV-TDF-FTC Control group

Rilpivirine-TDF-FTC in HIV-HCV-Coinfected Patients

hEPAtic: Result

Grade 3-4 Transaminase Elevation, by Degree of Hepatic Fibrosis

Source: Neukam K, et al. PLoS One. 2016;11:e0155842.

2 5 2

2 4 6 8

RPV-TDF-FTC Control group

Patients (%) F0-F2 F3-F4

Rilpivirine-FTC-TDF in HIV-HCV Coinfected Patients

hEPAtic: Result

Grade 3-4 Transaminase Elevation, by Presence of Cirrhosis

Source: Neukam K, et al. PLoS One. 2016;11:e0155842.

2 4 3

2 4 6 8 10

RPV-TDF-FTC Control group

Patients (%) No cirrhosis Cirrhosis

Rilpivirine-FTC-TDF in HIV-HCV Coinfected Patients

hEPAtic: Conclusions

Source: Neukam K, et al. PLoS One. 2016;11:e0155842.

Conclusion: “The frequency of severe liver toxicity in HIV/HCV- coinfected subjects receiving EPA under real-life conditions is very low, TE were generally mild and did not lead to drug discontinuation. All these data suggest that EPA can be safely used in this particular subpopulation.”

Rilpivirine-Tenofovir DF-Emtricitabine

NONOCCUPATIONAL PEP

Rilpivirine-Tenofovir DF-Emtricitabine as PEP in MSM

EPEP Study

RPV-TDF-FTC as Postexposure Prophylaxis in MSM

EPEP: Study Design

Source: Foster R, et al. Clin Infect Dis. 2015;61:1336-41.

Study Design: EPEP Study

• Background: Open-label, single-arm study

evaluating the adherence and efficacy of RPV-TDF- FTC as a single-tablet regimen for PEP in men who have sex with men (MSM)

• Inclusion Criteria (n = 100)
• Age ≥18 years
• Healthy MSM without HIV infection
• Eligible for 3-drug PEP based on exposure risk
• No resistance to study drugs
• No previous RPV-TDF-FTC for PEP
• No hepatitis B infection
• Postexposure Prophylaxis Regimen
• Rilpivirine-tenofovir DF-emtricitabine

RPV-TDF-FTC

(n = 100)

Week 12 Week 0

RPV-TDF-FTC as Postexposure Prophylaxis in MSM

EPEP: Result

Week 4: PEP Completion or Premature Cessation

Source: Foster R, et al. Clin Infect Dis. 2015;61:1336-41.

92 6 1 1 20 40 60 80 100 PEP completion Lost to follow-up Cessation due to adverse event Cessation due to study burden Patients (%)

RPV-TDF-FTC as Postexposure Prophylaxis in MSM

EPEP: Result

Week 4: Adherence to 28-day PEP Regimen

Source: Foster R, et al. Clin Infect Dis. 2015;61:1336-41.

99 99 88 20 40 60 80 100 By pill count By self-report By plasma tenofovir level Patients (%)

Adherence Measure

RPV-TDF-FTC as Postexposure Prophylaxis in MSM

EPEP: Result

PEP Efficacy Among Patients Completing 12 Weeks of Follow-up (n=70)

Source: Foster R, et al. Clin Infect Dis. 2015;61:1336-41.

Number of cases of HIV acquisition at week 12:

RPV-TDF-FTC as Postexposure Prophylaxis in MSM

EPEP: Conclusions

Source: Foster R, et al. Clin Infect Dis. 2015;61:1336-41.

Conclusions: “A single-tablet regimen of FTC-RPV-TDF was well tolerated as once-daily PEP, with high levels of adherence and completion.”

Acknowledgment

The National HIV Curriculum is an AIDS Education and Training Center (AETC) Program supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) as part of an award totaling $800,000 with 0% financed with non-governmental sources. This project is led by the University of Washington’s Infectious Diseases Education and Assessment (IDEA) Program.

The content in this presentation are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by HRSA, HHS, or the U.S. Government.