MED—US-6311
Feb-23 1
Patient Reported Outcomes from ATLAS and FLAIR
Summary
• In the pooled analysis of ATLAS and FLAIR:
o Treatment satisfaction with and acceptance of long-acting cabotegravir and rilpivirine
(CAB + RPV LA) increased from baseline through Weeks 44 and 48, respectively.
o Acceptability of injection site reactions improved statistically from Week 5 through Weeks
41 and 48.
• Eighty-eight percent of patients preferred CAB + RPV LA over the daily antiretroviral therapy
(ART) they were receiving previously. Among patients who responded to the question, 98%
preferred CAB + RPV LA.
• Important Safety Information can be found in the Prescribing Information and also at Our
HIV Medicines.
To access additional scientific information related to ViiV Healthcare
medicines, visit the ViiV US Medical Portal at viivhcmedinfo.com.
Patient reported outcomes were assessed in ATLAS and FLAIR utilizing multiple instruments as well one
single-item question on participant preference for CAB + RPV LA.
1,2
See Table 1 below.
Table 1. Patient Reported Outcomes Assessments in ATLAS and FLAIR
1,2
Instrument
Assessment
Timepoints
Pooled
Analysis
Secondary Endpoints (pre-specified)
HIV Treatment
Satisfaction
Questionnaire
(HIVTSQs/c)
Patient satisfaction with HIV treatment
Status: maintenance
baseline, W4, W24,
W44
Change: W48
✔
Chronic Treatment
Acceptance
(ACCEPT)
Patient acceptance of treatment
Maintenance baseline,
W8, W24, W48
✔
Perception of
Injection (PIN)
questionnaire
Tolerability of pain and injection-site reactions
W5, W41, W48
✔
Short Form Health
Survey (SF-12)
General health status and degree of mental
health distress
Maintenance baseline,
W24, W48
HIV/AIDS Targeted
Quality of Life (HAT-
QoL)
Overall function and wellbeing. Only 3 out of 9
dimensions were assessed.
Maintenance baseline,
W24, W48
Numeric Rating
Scale (NRS)
Intensity of post-injection pain
W4, W5, W40, W41
Exploratory Endpoints (pre-specified)
Preference of HIV
treatment (single
question)
Patient preference for CAB + RPV LA versus
CAR
W48
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Reason for switch
(single question)
Patient reasoning for switching to LA therapy
from oral therapy for ATLAS study only
D1, W52
ATLAS = Antiretroviral Therapy Long-Acting Suppression; FLAIR = First Long-Acting HIV Injectable Regimen; s/c = status and
change versions; W = week; CAB + RPV LA = long-acting cabotegravir and rilpivirine; CAR = current antiretroviral regimen; D =
day
HIVTSQ
Treatment satisfaction was assessed using a recent adaptation of the validated 10-item HIVTSQ, in which
two additional items were added to account for changes in HIV treatments, including the recent
development of injectable long-acting formulations.
1-4
In the pooled analysis, patients in the CAB + RPV LA arm had significantly greater improvements from
baseline compared to CAR in treatment satisfaction (HIVTSQ[s]) to Week 24 and Week 44.
5
See Table 2
below.
Table 2. Change from Baseline in Total Treatment Satisfaction Score by Visit (ITT-E, Maintenance
Phase) Assessed with HIVTSQs in ATLAS and FLAIR
5
Treatment
n
Adjusted Mean
(95% CI)
*
Adjusted Mean
Difference (95% CI)
P value
ATLAS
CAB + RPV LA
300
6.4 (5.6, 7.3)
5.39 (4.2, 6.6)
<0.001
CAR
288
1.1 (0.2, 1.9)
CAB + RPV LA
300
6.1 (5.2, 7.0)
5.68 (4.4, 7.0)
<0.001
CAR
294
0.4 (−0.5, 1.4)
FLAIR
CAB + RPV LA
257
1.6 (0.8, 2.5)
2.2 (1.0, 3.4)
<0.001
CAR
253
−0.5 (−1.4, 0.3)
CAB + RPV LA
257
1.3 (0.5, 2.1)
0.7 (−0.4, 1.9)
0.217
CAR
256
0.5 (−0.3, 1.4)
Pooled
CAB + RPV LA
557
4.2 (3.6, 4.8)
3.9 (3.0, 4.8)
<0.001
CAR
543
0.3 (−0.3, 0.9)
CAB + RPV LA
557
3.9 (3.2, 4.5)
3.4 (2.5, 4.3)
<0.001
CAR
552
0.5 (−0.1, 1.2)
*adjusted for baseline score, sex, age, and race.
ATLAS = Antiretroviral Therapy Long-Acting Suppression; FLAIR = First Long-Acting HIV Injectable Regimen; CI = confidence
interval; CAB + RPV LA = long-acting cabotegravir and rilpivirine; CAR = current antiretroviral regimen
In FLAIR, high mean baseline scores were reported in the CAB + RPV LA and CAR groups indicating high
satisfaction with HIV treatment at baseline.
5
Statistically significant greater improvements in treatment
satisfaction in the CAB + RPV LA group compared to the CAR group were achieved at Week 24 but were
not maintained through Week 44 partly because of an increase in treatment satisfaction for the CAR group
from Week 24 to Week 44. Importantly, the high mean baseline scores for the HIVTSQs in FLAIR led to
ceiling effects with the use of HIVTSQs which limits the possibility of detecting a significant increase in
mean difference between treatment groups.
To account for these ceiling effects, the HIVTSQc was used at Week 48.
5
The HIVTSQc, administered only
at Week 48, compares subjects' experiences with their treatment compared with their treatment prior to
entering the study. Results can be found in Table 3 below.
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Table 3. Treatment Satisfaction Assessed with HIVTSQc in FLAIR at Week 48
5
Treatment
n
Adjusted Mean
(SE)*
Adjusted Mean
Difference (95% CI)
P value†
CAB + RPV LA
263
29.6 (0.49)
4.1 (2.8, 5.5)
<0.001
CAR
266
25.5 (0.48)
*adjusted for induction baseline HIV-1 RNA, sex at birth, age, and race.
†statistical significance can be claimed in the P value is less than the Bonferroni adjusted alpha of 0.0027
FLAIR = First Long-Acting HIV Injectable Regimen; SE = standard error; CAB + RPV LA = long-acting cabotegravir and
rilpivirine; CAR = current antiretroviral regimen
ACCEPT
The ACCEPT questionnaire is a generic medication acceptance measure validated for chronic conditions to
assess how participants weigh advantages and disadvantages of long-term medications.
6
While the ACCEPT
questionnaire consists of 25 items that capture six dimensions, only the three questions that focus on
General Acceptance of study medication were used in these studies.
1,2
The pooled analysis showed that patients in the CAB + RPV LA group had statistically significant
improvements in the overall acceptance of HIV treatment compared with the CAR group at each timepoint.
5
See Table 3 below.
Table 3. Change from Baseline in General Acceptance Domain of ACCEPT in ATLAS and FLAIR
5
Treatment
n
Adjusted Mean
(95% CI)
*
Adjusted Mean
Difference (95% CI)
P-value
ATLAS
CAB + RPV LA
302
8.9 (6.3, 11.6)
7.9 (4.1, 11.7)
<0.001
CAR
287
1.0 (−1.7, 3.8)
CAB + RPV LA
303
12.3 (9.9, 14.8)
6.9 (3.3, 10.4)
<0.001
CAR
295
5.5 (3.0, 8.0)
CAB + RPV LA
302
13.7 (11.2, 16.3)
10.7 (7.1, 14.4)
<0.001
CAR
298
3.0 (0.4, 5.6)
FLAIR
CAB + RPV LA
253
3.3 (0.8, 5.8)
2.2 (−1.4, 5.7)
0.232
CAR
256
1.2 (−1.3, 3.6)
CAB + RPV LA
255
3.7 (1.1, 6.4)
2.7 (−1.0, 6.4)
0.154
CAR
261
1.1 (−1.5, 3.7)
CAB + RPV LA
255
3.0 (0.4, 5.6)
2.2 (−1.4, 5.8)
0.236
CAR
262
0.8 (−1.7, 3.4)
Pooled
CAB + RPV LA
555
6.3 (4.4, 8.1)
5.0 (2.4, 7.7)
<0.001
CAR
545
1.2 (−0.7, 3.1)
CAB + RPV LA
558
8.4 (6.6, 10.2)
5.0 (2.4, 7.5)
<0.001
CAR
558
3.4 (1.6, 5.2)
CAB + RPV LA
557
8.8 (7.0, 10.6)
6.8 (4.2, 9.4)
<0.001
CAR
562
2.0 (0.2, 3.8)
*adjustments by trial - ATLAS: baseline score, sex at birth, age, race and third agent class; FLAIR: maintenance baseline score,
induction baseline score, induction baseline HIV-1 RNA, sex at birth, age, and race; POOLED: maintenance baseline score, sex
at birth, age, and race.
ATLAS = Antiretroviral Therapy Long-Acting Suppression; FLAIR = First Long-Acting HIV Injectable Regimen; CI = confidence
interval; CAB + RPV LA = long-acting cabotegravir and rilpivirine; CAR = current antiretroviral regimen
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PiN
The PiN questionnaire explores the bother of pain at the injection site and injection site reactions (ISR),
anxiety before and after injection, willingness to receive an HIV injectable treatment the following visit and
satisfaction with the mode of treatment administration of individuals receiving injection and perceptions
of individuals associated with receiving injections.
1,2
The PiN questionnaire was derived from the validated
Vaccines' Perception of Injection (VAPI) questionnaire, and adapted for HIV-infected participants who
received CAB + RPV LA.
7
Four domains were assessed: Acceptance, Bother of ISRs, Leg Movement, and Sleep.
1,2
Patients were asked
to respond to 21 questions related to these domains, as well as 5 individual questions not part of the
domains, on a scale of 1 to 5 where 1=Totally Acceptable, 2=Very Acceptable, 3=Moderately Acceptable,
4=A Little Acceptable, and 5=Not at all Acceptable. Only the change from Week 5 to Weeks 41 and 48 were
analyzed statistically.
Results from the PiN can be found in Figure 1. Only Acceptance was analyzed statistically.
8
The differences
between Week 5 and Weeks 41 and 48 were statistically significant (P < 0.001)
Figure 1. Median Domain Scores Assessed with the PiN Questionnaire
8
*The differences between Week 5 and Weeks 41 and 48 were statistically significant (P<0.001)
SF-12
The SF-12 is a measure that describes the degree of general health status and mental health distress and
contains 12 items derived from the Medical Outcomes Study 36-Item Short Form Health Survey.
9
No statistically significant difference in change from baseline in SF-12 physical component score (PCS) and
mental component score (MCS) was observed between treatment groups at any measured visit in ATLAS
and FLAIR.
HAT-QoL (short form)
The HAT-QoL instrument originally contained 42 items, grouped into nine dimensions, assessing overall
function and well-being.
10
For the purposes of these studies, a shorter version adapted from the original
was used.
1,2
This shorter version contains 14 items grouped into the following dimensions: Life Satisfaction,
Disclosure Worries, and HIV Medication.
1 1
1
2
3
4
5
Week 5 Week 41 Week 48
Domain Score (1
-5)
Acceptance* Bother of ISRs Leg movement Sleep
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Life Satisfaction
No statistically significant difference in change from baseline in Life Satisfaction score was observed in
either treatment in ATLAS and FLAIR.
11,12
Disclosure Worries
In ATLAS and FLAIR minor differences between treatment groups were observed in change from baseline
in Disclosure Worries that have not been maintained across all timepoints.
11
HIV Medication
In ATLAS, at Baseline, no differences in HIV Medication scores were found between treatment groups.
11
Subjects in the CAB + RPV LA group demonstrated a statistically significantly greater improvement from
Baseline in HIV Medication score compared with subjects on the CAR group at Weeks 24 and 48.
In FLAIR, minor numerical improvements from baseline were reported in both treatment groups at Weeks
24 and 48.
12
No statistically significant difference in change from baseline in HIV Medication score was
observed between treatment groups
NRS
The NRS is a segmented numeric version of the visual analog scale in which a respondent selects a whole
number (0–10) that best reflects the intensity of his/her post-injection pain.
1,2
The NRS is anchored by 0
representing No Pain and 10 representing Extreme Pain.
The NRS was used to assess maximum level of pain on the day of the injection (at Weeks 4b and 40) and
one week following injections (Weeks 5 and 41).
1,2
The assessment was only given to subjects on the CAB +
RPV LA group.
Table 4. Intensity of Post-Injection Pain in ATLAS and FLAIR through Week 41
11,12
Timing Relative to
Injection
Timepoint
ATLAS
Median
(IQR)
[min-max]
FLAIR
Median
(IQR)
[min-max]
Immediately Post
Injection
Week 4b
1.0
(0.0-3.0)
[0.0-10.0]
n=273
2.0
(0.0-3.0)
[0.0-9.0]
n=261
Week 40
1.5
(0.0-3.0)
[0.0-10.0]
n=260
2.0
(1.0-4.0)
[0.0-8.0]
n=224
1 Week Post Injection
Week 5
3.0
(1.0-6.0)
[0.0-10.0]
n=263
4.0
(1.0-7.0)
[0.0-10.0]
n=232
Week 41
1.0
(1.0-3.0)
[0.0-10.0]
n=227
2.0
(1.0-3.0)
[0.0-8.0]
n=214
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Preference
Patients in the CAB + RPV LA arm of both studies were asked the following at Week 48
1,2
:
“For the past 44 weeks you have received long acting injectable HIV medication every month. Today we
would like you to compare your experience on the long acting injections with the oral medication you
received previously. Which therapy do you prefer?”
Participants had the option of selecting either “Daily Oral HIV Treatment” or “Monthly Injections of Long-
Acting HIV Treatment.”
At Week 48, 88% (523/591) preferred CAB + RPV LA over the daily oral medication they were receiving
previously.
11,12
Among patients who responded to the question (532/591), 98% (523/532) preferred CAB +
RPV LA over daily ART.
Reason for Switch (ATLAS only)
The Reason for Switch question contained a single item exploring the reasons why patients chose to switch
study medication.
1
The single item included six possible response options.
At Day 1, all patients responded to the Reason for Switch question.
11
The top 2 reasons for wanting to change
therapies were “I am interested in research of new therapies” (82%, 505/616) and “my clinician asked me
to participate” (25%, 151/616).
At Week 52, subjects switching to CAB + RPV LA group from the CAR group indicated “interest in the
convenience of a monthly injectable treatment” (53%, 164/308) and “discretion associated with a monthly
injectable treatment” (32%, 98/308) as the top 2 reasons for switching over to the Extension Phase of the
study.
11
Some information contained in this response may not be included in the approved Prescribing
information. This response is not intended to offer recommendations for administering this
product in a manner inconsistent with its approved labeling. Please note that reports of adverse
events in the published literature often lack causality assessments and may contain incomplete
information; therefore, conclusions about causality generally cannot be drawn.
In order for ViiV Healthcare to monitor the safety of our products, we encourage healthcare
professionals to report adverse events or suspected overdoses to the company at 877–844–8872.
Please consult the attached Prescribing Information.
This response was developed according to the principles of evidence-based medicine and,
therefore, references may not be all-inclusive.
REFERENCES
1. ClinicalTrials.gov identifier NCT02951052. Available at: https://ClinicalTrials.gov/show/NCT02951052.
2. ClinicalTrials.gov identifier NCT02938520. Available at: https://ClinicalTrials.gov/show/NCT02938520.
3. Woodcock A, Bradley C. Validation of the HIV treatment satisfaction questionnaire (HIVTSQ). Qual Life
Res. 2001;10(6):517-531
4. Woodcock A, Bradley C. Validation of the revised 10-item HIV Treatment Satisfaction Questionnaire status
version and new change version. Value Health. 2006;9(5):320-333. doi:http://dx.doi.org/10.1111/j.1524-
4733.2006.00121.x.
5. ViiV Healthcare, Module 5.3.5.3, Integrated Summary of Efficacy for cabotegravir, version 2.0, March 19,
2019.
6. Marant C, Longin J, Gauchoux R, et al. Long-term treatment acceptance: what is it, and how can it be
assessed? Patient. 2012;5(4):239-249. doi:http://dx.doi.org/10.2165/11631340-000000000-00000.
7. Chevat C, Viala-Danten M, Dias-Barbosa C, Nguyen VH. Development and psychometric validation of a self-
administered questionnaire assessing the acceptance of influenza vaccination: the Vaccinees' Perception of
Injection (VAPI) questionnaire. Health Qual Life Outcomes. 2009;7:21. doi:http://dx.doi.org/10.1186/1477-
7525-7-21.
8. ViiV Healthcare, Module 5.3.5.3, Integrated Summary of Safety for cabotegravir, version 2.0, March 29,
2019.
9. Ware J, Jr., Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and
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preliminary tests of reliability and validity. Med Care. 1996;34(3):220-233.
doi:http://dx.doi.org/10.1097/00005650-199603000-00003.
10. Holmes WC, Shea JA. A new HIV/AIDS-targeted quality of life (HAT-QoL) instrument: development,
reliability, and validity. Med Care. 1998;36(2):138-154. doi:http://dx.doi.org/10.1097/00005650-
199802000-00004.
11. Data on File. ATLAS (Study 201585). Available at http://www.viiv-studyregister.com.
12. Data on File. FLAIR (Study 201584). Available at http://www.viiv-studyregister.com.