XIX International AIDS Conference

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Efficacy and safety outcomes for rilpivirine (RPV) versus efavirenz (EFV) plus emtricitabine/tenofovir DF (FTC/TDF) in treatment-naïve, HIV-1-positive adults with baseline viral load ≤ 100,000 copies/mL-pooled 48-week ECHO and THRIVE analysis

Presented by Calvin Cohen (United States).

G. Behrens1, B. Rijnders2, M. Nelson3, C. Orkin4, C. Cohen5, K. Boven6, L. Rimsky7, K. White8, J. DeMorin8, D. Thorpe9, M. Bosse9, L. Zhong8, S. Chuck8


1Medical School of Hannover, Clinic for Immunology and Rheumatology, Hannover, Germany, 2Erasmus Medical Centre, Internal Medicine- D418, Rotterdam, Netherlands, 3Chelsea & Westminster Hospital, Thomas McCauley Ward, London, United Kingdom, 4Barts and the London NHS Trust, London, United Kingdom, 5Community Research Initiative of New England, Boston, United States, 6Janssen Research & Development LLC, Titusville, United States, 7Janssen Infectious Diseases BVBA, Beerse, Belgium, 8Gilead Sciences, Inc., Foster City, United States, 9Gilead Sciences, Inc., Stockley Park, United Kingdom

Background: At Week 48, RPV+FTC/TDF demonstrated high virologic response and non-inferiority to EFV+FTC/TDF overall and by baseline HIV-1 RNA (BLVL) above or below 100,000copies/mL in the pooled ECHO and THRIVE studies. However, there were more virologic failures (VF) at higher BLVL. The increasing availability of the single-tablet regimen FTC/RPV/TDF around the world, in addition to the European Medicines Agency's (EMEA) approval of FTC/RPV/TDF for use in HIV-1 infected, antiretroviral-naïve adults with BLVL ≤100,000copies/mL makes an analysis of efficacy, safety, and resistance outcomes for RPV subjects receiving FTC/TDF with BLVL ≤100,000copies/mL particularly relevant.
Methods: ECHO and THRIVE subjects with BLVL ≤100,000copies/mL who received FTC/TDF with either RPV (N=288) or EFV (N=256) were included in this 48-week post-hoc, pooled analysis of efficacy, safety and resistance outcomes.
Results: Of the 544 subjects, 75% were male, 59% White race, 26% Black race, median age 36 years, median BLVL 4.5 log10 copies/mL, and median CD4 279 cells/mm3. For subjects with BLVL ≤100,000copies/mL, RPV+FTC/TDF was non-inferior to EFV+FTC/TDF with higher virologic response (VR) of 90% vs. 85% [VL< 50copies/mL, ITT-TLOVR; 95%CI: 5% (-0.8%, 10.5%)]. In both treatment arms, VR was ~20% lower with self-reported adherence ≤95% vs. >95% and VF rates were low for RPV+FTC/TDF and EFV+FTC/TDF (4.2% and 2.3%). There were fewer discontinuations due to adverse events (AEs) with RPV+FTC/TDF (2% vs. 6%). Mean CD4 increases from baseline were similar (202 and 195cells/mm3), respectively.

Virologic Outcome (ITT-TLOVR), n (%)RPV+FTC/TDF
N=288
EFV+FTC/TDF
N=256
p-value or 95% CI
Virologic Responder (HIV-1 RNA <50copies/mL)258 (90)217 (85)5% (-0.8%, 10.5%)
Virologic Failure*
- Rebounder
- Never Suppressed
12 (4)
7 (2)
5 (2)
6 (2)
6 (2)
0
0.337
1
0.064
Discontinued due to AE7 (2)16 (6)0.033
Discontinued due to other reason? than AE11 (4)17 (7)0.174
Death00ND
*Virologic failure = virologic failure determined by TLOVR in the ITT population: confirmed response before Week 48 and confirmed rebound (rebounders) at or before Week 48, or no confirmed response before Week 48 (never suppressed)
?Lost to follow-up, non-compliance, withdrew consent, ineligible to continue, sponsor's decision
ND=Not done
[Virologic Outcome by ITT-TLOVR in BL VL ≤100K]



Genotypic Resistance*RPV+FTC/TDF
N=288
EFV+FTC/TDF
N=256
Genotypic data, n146
Developing any NNRTI RAMs, n/N(%)
- K103N, n
- E138K, n
4/288 (1)

0
3
2/256 (1)

2
0
Developing any N(t)RTI RAMs, n/N(%)
- M184I/V, n
- K65R, n
5/288 (2)

5
0
0

0
0
RAMs = resistant associated mutations
*Virologic Failure in resistance analysis = all ITT patients with virologic failure regardless of time of failure and/or discontinuation reason provided the following criteria were met: first achieved two consecutive viral load values <50 copies/mL followed by two consecutive (or single, when last available) viral load values ≥50 copies/mL or never achieved two consecutive viral load values <50 copies/mL and had an increase in viral load ≥0.5 log10 copies/mL above the nadir (never suppressed)
[Resistance in BL VL ≤100K]



Incidence of Select Adverse Events & Lab Abnormalities, n (%)RPV+FTC/TDF
N=288
EFV+FTC/TDF
N=256
p-value
Treatment-related Grade 2-4 AEs46 (16)74 (29)0.0004
Treatment-related Neurologic AEs
- Somnolence
- Dizziness
- Disturbance in attention
54 (19)

8 (3)
30 (10)
2 (1)
99 (39)

16 (6)
72 (28)
6 (2)
< 0.0001

0.06
< 0.0001
0.16
Treatment-related Psychiatric AEs
- Abnormal dreams/nightmares
44 (15)

21 (7)
59 (23)

34 (13)
0.02

0.02
Grade 3+ laboratory abnormalities
- Aspartate aminotransferase
- Alanine aminotransferase
23 (8)

12 (4)

14 (5)
39 (16)

25 (10)

26 (10)
0.01

0.01

0.02
Grade 2+ lipids abnormalities
- Total cholesterol (>6.2mmol/L; >240mg/dL)
- LDL-cholesterol (>4.13mmol/L; >160mg/dL)


11 (4)


16 (6)




45 (18)


33 (13)




<0.0001


0.003


Treatment-related = At least possibly related to treatment
[Summary of Adverse Events & Labs Abnormalities]


Conclusions: In subjects with BLVL ≤100,000copies/mL, RPV+FTC/TDF demonstrated non-inferior virologic efficacy to EFV+FTC/TDF with low VF rates at Week 48. Overall, RPV+FTC/TDF had an improved safety profile vs. EFV+FTC/TDF with significantly less Grade 2-4 AEs, treatment-related neurologic and psychiatric AEs, dizziness, abnormal dreams/nightmares, Grade 3+ laboratory abnormalities, Grade 2+ total cholesterol and LDL- cholesterol. While RPV+FTC/TDF subjects had more N(t)RTI RAMs than EFV+FTC/TDF, few subjects developed NNRTIs RAMs in both treatment groups.

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