exclusion criteria - amazon s3 · 2019-10-04 · subjects aged >=18 years of age at index date....

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The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. GSK Medicine: Dolutegravir Study Number: 209557 Title: Using Climate-HIV to understand real-world drug-drug interactions and clinical outcomes for people living with HIV Rationale: Human immunodeficiency virus (HIV) subjects are usually prescribed with five or more medications simultaneously which increases the risk of serious adverse drug events and drug-drug interactions. As the population of people living with HIV (PLWHIV) are growing older and diagnosed with more comorbidities, therapeutic advances in HIV aim to reduce the potential for drug-drug interactions (DDIs). This study aims to describe the non-antiretroviral (ARV) treatments prescribed to PLWHIV and potentials DDIs and clinical outcomes of subjects initiating dolutegravir (DTG)-based regimens. Study Period: 05-Dec-2017 to 31-Jul-2019 Objectives:

1) To describe non-ARV drug use among PLWHIV in terms of: o The proportion of subjects recording concomitant non-ARV medications and/or conditions. o The proportion of subjects with potential DDIs identified between ARV agents and the

collated non-ARV medications (population level). 2) To describe subject characteristics and clinical outcomes for treatment experienced and treatment

naive subjects initiating DTG-based regimens according to: o The change in HIV viral load between Baseline and follow-up. o Proportion of subjects switching or discontinuing DTG-based regimens and the reason for

change or switch, where available. Indication: HIV Infections Study Investigators/Centers: ViiV healthcare conducted study. Research Methods: The study consisted of two cohorts: one for the DDIs and another for clinical outcomes. Subjects with HIV receiving care at participating hospital trusts captured by Climate-HIV (North Middlesex University Hospital National health services [NHS] Trust, Nottingham University Hospitals NHS Trust, Birmingham Heartlands Hospital, and Homerton University Hospital NHS Foundation Trust) were enrolled for the study. Data Source: Data was collected from the Climate-HIV care record system. Climate-HIV is a specialized electronic patient record (EPR) system for HIV medicine designed by clinicians at North Middlesex University Hospital Trust in London. For this study, data was captured from North Middlesex University Hospital NHS Trust, Nottingham University Hospitals NHS Trust, Birmingham Heartlands Hospital and Homerton University Hospital NHS Foundation Trust. Study Design: This study utilized cross sectional study design for objective 1 and retrospective cohort design for objective 2. Study Population: Objective 1: Inclusion Criteria:

Recorded diagnosis of HIV-1. Subjects aged >=18 years of age at index date. Subjects who are permanently registered at the clinic (or who have a record [e.g., prescription,

consultation] within the 18 months prior to index date for sites without “permanent registration” criteria). Prescribed ARV regimen within the year prior to index date.

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Exclusion Criteria: Incarcerated subjects were also excluded.

Objective 2: Inclusion Criteria:

Recorded diagnosis of HIV-1. First prescription for a DTG-based regimen is received during the study time period. Subjects aged >=18 years of age at index date. A Baseline viral load measurement recorded within the 9 months prior to index date.

Exclusion Criteria:

Diagnosed with HIV-2 by confirmatory antibody test or HIV-2 viral load. Treated with an HIV-1 vaccine prior to index date. Incarcerated subjects..

Study Exposures, Outcomes: Exposures of interest included ARV and non-ARV treatments. Outcomes based on objective 1:

DDIs between ARV and non-ARV medication. Outcomes based on objective 2:

Proportion of subjects with HIV viral load <50 copies per milliliter (/mL) at 24, 48, 96 weeks of follow-up and last recorded measurement.

Change in cluster of differentiation (CD4+) count at 24, 48, and 96 weeks of follow-up and last recorded measurement.

Treatment failure (treatment switch or discontinuation of a DTG-based regimen for any reason; analyzed at 24, 48, 96 weeks, and overall).

Proportion of subjects who had a resistance test and number of subjects with new resistance mutation following initiation of DTG.

Virological failure. Switch/Discontinuation of DTG.

Data Analysis Methods: The HIV viral loads were log-transformed for analysis. Descriptive analysis was performed using number and percent within category with 95 percent (%) confidence intervals for categorical variables, and mean (with 95% confidence interval), median, standard deviation (SD), interquartile range (IQR), minimum and maximum for continuous variables. Limitations:

Data for the study derived from four selected sites in England so it may not represent the entire population within England or the United Kingdom (UK).

The risk of non-differential misclassification, missing prescription data exist because the prescription subjects received in setting outside of climate-HIV may not have been included or coded.

Subjects who discontinued ARV treatment earlier were not captured in the analysis because this study intends to reflect current clinical practice in treatment recording and ARV therapy which could lead to an underestimation of potential DDIs.

The reason for switch or discontinuation were frequently input as “missing” by clinicians, which may have led to relative over- or under-estimation of identified reason for discontinuation.

There is a chance of subjects misclassification as treatment naive (TN) due to the presence of clinical visits, prior viral load test, and long medical histories available in Climate-HIV.

Study Results: Baseline characteristics for subjects included in objective 1

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Variable At index overall n=4630

Female n=2021

Male n=2609

Age in years at index Mean (SD) 46.97 (11.42 ) 45.95 (10.53 ) 47.77 (12.01 ) Index: The index date was the most recent record within Climate-HIV. Ethnicity, n (%) Asian 155 (3.35) 40 (1.98) 115 (4.41) Black African 2064 (44.58) 1345 (66.55) 719 (27.56) Black Caribbean / Other

446 (9.63) 220 (10.89) 226 (8.66)

Mixed 167 (3.61) 90 (4.45) 77 (2.95) Unknown 216 (4.67) 84 (4.16) 132 (5.06) White 1582 (34.17) 242 (11.97) 1340 (51.36) Number of concomitant non-ARV drugs by category, n (%) Variable Overall Age <50 years Age >=50 years 0 1638 (35.38) 1176 (43.05) 462 (24.34) 1 797 (17.21) 515 (18.85) 282 (14.86) 2 664 (14.34) 394 (14.42) 270 (14.23) 3 465 (10.04) 249 (9.11) 216 (11.38) 4 296 (6.39) 136 (4.98) 160 (8.43) 5 226 (4.88) 88 (3.22) 138 (7.27) 6 147 (3.17) 56 (2.05) 91 (4.79) 7 102 (2.2) 38 (1.39) 64 (3.37) 8+ 295 (6.37) 80 (2.93) 215 (11.33) Number of health conditions by category, n (%) Variable Overall Age <50 years Age >=50 years 0 2792 (60.3) 1847 (67.61) 945 (49.79) 1 1224 (26.44) 676 (24.74) 548 (28.87) 2 453 (9.78) 163 (5.97) 290 (15.28) 3 111 (2.4) 37 (1.35) 74 (3.9) 4 41 (0.89) 8 (0.29) 33 (1.74) 5+ 9 (0.19) 1 (0.04) 8 (0.42) ARV and non-ARV interactions for the overall population

Comed

Number of subjects on comed

ATV+2NRTIs N=75 n (%)

DRV+2NRTIs N=342 n (%)

DTG+2NRTIs N=491 n (%)

EFV+2 NRTIs N=462 n (%)

ELV+2NRTIs N=38 n (%)

NVP+2NRTIs N=264 n (%)

RAL+2NRTIs N=216 n (%)

RPV+2NRT

Is N=55 n (%)

Sildenafil* 82 2 (0.1)

R 18 (0.9)

R 20 (1.0)

G 11 (0.5)

A 0 (0.0)

R 9 (0.4)

A 14 (0.7)

G

8 (0.4)

G

Quetiapine 22 1 (0.0)

R 4 (0.2)

R 11 (0.5)

G 1 (0.0)

A 0 (0.0)

R 3 (0.1)

A 1 (0.0)

G

1 (0.0)

Y

Lansoprazole 165 0 (0.0)

R 32 (1.6)

A 50 (2.4)

G 27 (1.3)

G 3 (0.1)

A 21 (1.0)

G 29 (1.4)

G

3 (0.1)

R

4

Omeprazole 118 2 (0.1)

R 20 (1.0)

A 38 (1.9)

G 22 (1.1)

G 3 (0.1)

A 14 (0.7)

G 19 (0.9)

G

0 (0.0)

R

Norethisterone 8 1 (0.0)

A 0 (0.0) A 3 (0.1)

G 2 (0.1)

R 0 (0.0)

A 1 (0.0)

Y 0 (0.0)

G

1 (0.0)

G

Desogestrel 11 0 (0.0)

A 0 (0.0) A 4 (0.2)

G 2 (0.1)

R 0 (0.0)

A 2 (0.1)

Y 2 (0.1)

G

1 (0.0)

G

Etonogestrel 5 0 (0.0)

A 0 (0.0) A 2 (0.1)

G 2 (0.1)

R 0 (0.0)

A 0 (0.0)

Y 0 (0.0)

G

1 (0.0)

G

Ketoconazole 7 0 (0.0)

A 0 (0.0) A 3 (0.1)

A 1 (0.0)

R 1 (0.0)

A 0 (0.0)

R 1 (0.0)

A

1 (0.0)

A

Lercanidipine 4 0 (0.0)

R 1 (0.0)

R 0 (0.0)

G 1 (0.0)

A 0 (0.0)

R 2 (0.1)

A 0 (0.0)

G

0 (0.0)

G

Fluticasone 5 0 (0.0)

R 1 (0.0)

R 1 (0.0)

G 2 (0.1)

A 0 (0.0)

R 0 (0.0)

A 0 (0.0)

G

1 (0.0)

G

Levonorgestrel 2 0 (0.0)

A 0 (0.0) A 1 (0.0)

G 1 (0.0)

R 0 (0.0)

A 0 (0.0)

Y 0 (0.0)

G

0 (0.0)

G

Cholecalciferol 532 21 (1.0)

G 75 (3.7)

G 111

(5.4) A 138

(6.8) G 4 (0.2)

A 72 (3.5)

G 73 (3.6)

A

38 (1.9)

G

Amlodipine 236 6 (0.3)

A 31 (1.5)

A 41 (2.0)

G 64 (3.1)

A 1 (0.0)

A 42 (2.1)

A 27 (1.3)

G

24 (1.2)

G

Aciclovir 104 2 (0.1)

A 9 (0.4) A 24 (1.2)

A 22 (1.1)

A 4 (0.2)

A 16 (0.8)

A 15 (0.7)

A

12 (0.6)

A

Aspirin 99 1 (0.0)

A 15 (0.7)

A 24 (1.2)

A 19 (0.9)

A 2 (0.1)

A 19 (0.9)

A 16 (0.8)

A

3 (0.1)

A

Ibuprofen 90 2 (0.1)

A 17 (0.8)

A 29 (1.4)

A 16 (0.8)

A 1 (0.0)

A 12 (0.6)

A 10 (0.5)

A

3 (0.1)

A

Mirtazapine 118 5 (0.2)

A 27 (1.3)

A 39 (1.9)

G 9 (0.4)

A 5 (0.2)

A 16 (0.8)

A 10 (0.5)

G

7 (0.3)

G

Atorvastatin 253 7 (0.3)

A 38 (1.9)

A 47 (2.3)

G 53 (2.6)

Y 6 (0.3)

A 43 (2.1)

Y 41 (2.0)

G

18 (0.9)

G

Naproxen 49 6 (0.3)

A 6 (0.3) A 18 (0.9)

A 7 (0.3)

A 1 (0.0)

A 6 (0.3)

A 3 (0.1)

A

2 (0.1)

A Where A = Amber color, G = Green color, R = Red color and Y = Yellow color respectively. *The indication for sildenafil as for PAH or erectile dysfunction is not indicated in the data.

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ATV: Atazanavir, DRV: Darunavir, DTG: Dolutegravir, EFV: Efavirenz, ELV: Elvitegravir, NVP: Nevirapine, RAL: Raltegravir, RPV: Rilpivirine, NRTIs: Nucleoside Reverse Transcriptase Inhibitors Baseline characteristics for subjects included in objective 2

Overall n=934

TN n=217

TE n=717

Age in years at index Mean (SD) 42.36 (12.02) 38.29 (12.01) 43.59 (11.76) TE: Treatment experienced. Index: The index date was the first prescription of DTG during the study time period to include only new users. Gender, n (%)

Overall n=934

TN n=217

TE n=717

Female 337 (36.08) 58 (26.73) 279 (38.91) Male 597 (63.92) 159 (73.27) 438 (61.09) Ethnicity, n (%) Asian 42 (4.72) 14 (6.93) 28 (4.07) Black African 305 (34.27) 46 (22.77) 259 (37.65) Black Caribbean/Other

87 (9.78) 21 (10.4) 66 (9.59)

Mixed 42 (4.72) 11 (5.45) 31 (4.51) White 414 (46.52) 110 (54.46) 304 (44.19)

Clinical characteristic at 24 weeks post-DTG initiation

Covariate

Overall

TN TE

All TN subjects

Undetectable at index

Suppressed at index

Unsuppressed at index

All TE subjects

Undetectable at index

Suppressed at index

Unsuppressed at index

n = 934 n (%)

n = 217 n (%)

n = 14 n (%)

n = 4 n (%)

n = 199 n (%)

n = 717 n (%)

n = 506 n (%)

n = 65 n (%)

n = 146

n (%) Proportion of subjects with HIV viral load <50 copies/mL Undetectable (<50 copies/mL)

245 (83.05)

63 (84.00)

1 0 62 182

(82.73) 137 17 28

Subjects on 2 drug regimens at index

8 (3.27) 0 (0) 0 0 0 8 (4.4) 5 1 2

Subjects on all other regimens at index

237 (96.73)

63 (100)

1 0 62 174

(95.6) 132 16 26

Change in CD4+ count from Baseline (first recorded CD4+ cell count), among subjects with CD4+ cell count available at Baseline

Mean (SD)

119.8 (260.39)

61.75 (230.16

)

-114.33 (149.31)

-80 (76.37)

74.05 (232.53

)

143.35 (268.74)

193.19 (250.12

)

214.07 (270.11

)

-26.68 (255.9

5) Treatment failure (treatment switch or discontinuation of a DTG-based regimen for any reason

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Subjects who switched off DTG before snapshot, no. (%)

60 (6.42)

6 (2.76) 1 (7.14) 0 (0) 5 (2.51) 54

(7.53) 39

(7.71) 5 (7.69)

10 (6.85)

Subjects who discontinued DTG before snapshot, no. (%)

18 (1.93)

7 (3.23) 0 (0) 0 (0) 7 (3.52) 11

(1.53) 2 (0.4) 2 (3.08)

7 (4.79)

Proportion of subjects who had a resistance test and number of subjects with new resistance mutation following initiation of DTG Resistance Mutations since DTG initiation, among subjects who switched & took DTG once daily No Post-Initiation Resistance Test

57 (98.28)

6 (100) 1 (100) 0 5 (100) 51

(98.08) 38

(100) 4 (100) 9 (90)

No New Post-Initiation Resistances

1 (1.72) 0 (0) 0 (0) 0 0 (0) 1 (1.92) 0 (0) 0 (0) 1 (10)

Resistance to Other

0 (0) 0 (0) 0 (0) 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Resistance Mutations since DTG initiation, among subjects who switched and took DTG twice daily No Post-Initiation Resistance Test

1 (100) 0 0 0 0 1 (100) 0 1 (100) 0


0 (0) 0 0 0 0 0 (0) 0 0 (0) 0

Resistance to Other

0 (0) 0 0 0 0 0 (0) 0 0 (0) 0

Resistance Mutations since DTG initiation, among subjects who discontinued and took DTG once daily No Post-Initiation Resistance Test

17 (100) 7 (100) 0 0 7 (100) 10 (100) 2 (100) 2 (100) 6 (100)


0 (0) 0 (0) 0 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Resistance to Other

0 (0) 0 (0) 0 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Resistance Mutations since DTG initiation, among subjects who discontinued took DTG twice daily No Post-Initiation Resistance Test

1 (100) 0 0 0 0 1 (100) 0 0 1 (100)

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0 (0) 0 0 0 0 0 (0) 0 0 0 (0)

Resistance to Other

0 (0) 0 0 0 0 0 (0) 0 0 0 (0)

Virological failure Virological failure for any of the following reasons

34 (3.64)

14 (6.45)

2 (14.29)

0 (0) 12

(6.03) 20

(2.79) 9

(1.78) 4 (6.15)

7 (4.79)

1. [Primary virological failure] Subjects with viral load >=50 then >=200 copies/mL after previously undetectable and switch/discontinue

1 (0.11) 1 (0.46) 0 (0) 0 (0) 1 (0.5) 0 (0) 0 (0) 0 (0) 0 (0)

2. Subjects with 2 consecutive viral load measurements >=50 copies/mL after being previously undetectable

10 (1.07)

1 (0.46) 0 (0) 0 (0) 1 (0.5) 9 (1.26) 3

(0.59) 1 (1.54)

5 (3.42)

3. Subjects with viral load >=50 then >=200 copies/mL after being previously undetectable

16 (1.71)

5 (2.3) 1 (7.14) 0 (0) 4 (2.01) 11

(1.53) 6

(1.19) 3 (4.62)

2 (1.37)

4. Subjects with reason for switch/discontinue recorded as virological failure

0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

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5. Subjects with less than 1 log drop in viral load at 4 weeks (TN only)

7 (0.75) 7 (3.23) 1 (7.14) 0 (0) 6 (3.02) 0 (0) 0 (0) 0 (0) 0 (0)

6. Subjects with viral load >=400 copies/mL at 16 weeks (TN only)

0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Reason for switch (among all subjects who switched) recorded by clinician in Climate

Missing 19

(31.67) 2

(33.33) 0 (0) 0 2 (40)

17 (31.48)

12 (30.77)

1 (20) 4 (40)

Cost Reduction

9 (15) 0 (0) 0 (0) 0 0 (0) 9

(16.67) 8

(20.51) 0 (0) 1 (10)

Simplification 3 (5) 0 (0) 0 (0) 0 0 (0) 3 (5.56) 1

(2.56) 0 (0) 2 (20)

Clinician's decision

8 (13.33)

2 (33.33)

0 (0) 0 2 (40) 6

(11.11) 5

(12.82) 1 (20) 0 (0)

Subject Related

6 (10) 1

(16.67) 1 (100) 0 0 (0) 5 (9.26)

3 (7.69)

0 (0) 2 (20)

Renal 1 (1.67) 1

(16.67) 0 (0) 0 1 (20) 0 (0) 0 (0) 0 (0) 0 (0)

Gastrointestinal

2 (3.33) 0 (0) 0 (0) 0 0 (0) 2 (3.7) 2

(5.13) 0 (0) 0 (0)

Liver 1 (1.67) 0 (0) 0 (0) 0 0 (0) 1 (1.85) 1

(2.56) 0 (0) 0 (0)

CNS 1 (1.67) 0 (0) 0 (0) 0 0 (0) 1 (1.85) 0 (0) 0 (0) 1 (10)

Skin rash 2 (3.33) 0 (0) 0 (0) 0 0 (0) 2 (3.7) 2

(5.13) 0 (0) 0 (0)

Abdominal hypertrophy

0 (0) 0 (0) 0 (0) 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Osteopenia 1 (1.67) 0 (0) 0 (0) 0 0 (0) 1 (1.85) 1

(2.56) 0 (0) 0 (0)

Fatigue 1 (1.67) 0 (0) 0 (0) 0 0 (0) 1 (1.85) 0 (0) 1 (20) 0 (0) Adverse Reaction

0 (0) 0 (0) 0 (0) 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Swallowing difficulties

0 (0) 0 (0) 0 (0) 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

CD4 and VL failure

2 (3.33) 0 (0) 0 (0) 0 0 (0) 2 (3.7) 2

(5.13) 0 (0) 0 (0)

Viral Failure 0 (0) 0 (0) 0 (0) 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) CD4 Failure 1 (1.67) 0 (0) 0 (0) 0 0 (0) 1 (1.85) 0 (0) 1 (20) 0 (0) Resistance 0 (0) 0 (0) 0 (0) 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Drug 1 (1.67) 0 (0) 0 (0) 0 0 (0) 1 (1.85) 0 (0) 1 (20) 0 (0)

Other 2 (3.33) 0 (0) 0 (0) 0 0 (0) 2 (3.7) 2

(5.13) 0 (0) 0 (0)

VL: Viral load

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Reason for discontinuation (among all subjects who discontinued)

Missing 10

(55.56) 3

(42.86) 0 0

3 (42.86)

7 (63.64)

1 (50) 2 (100) 4

(57.14) Cost Reduction

0 (0) 0 (0) 0 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Simplification 1 (5.56)

1 (14.29)

0 0 1

(14.29) 0 (0) 0 (0) 0 (0) 0 (0)

Subject's own choice

3 (16.67)

0 (0) 0 0 0 (0) 3

(27.27) 0 (0) 0 (0)

3 (42.86)

CD4 and VL failure

1 (5.56) 1

(14.29) 0 0

1 (14.29)

0 (0) 0 (0) 0 (0) 0 (0)


0 (0) 0 (0) 0 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Other Reason given

3 (16.67)

2 (28.57)

0 0 2

(28.57) 1 (9.09) 1 (50) 0 (0) 0 (0)


Covariate

Overall TN TE

All TN

subjects

Undetectable

at index

Suppressed at index

Unsuppressed

at index

All TE Subject

s

Undetectabl

e at index

Suppressed at index

Unsuppresse

d at index

n = 934 n (%)

n = 217 n (%)

n = 14 n (%)

n = 4 n (%)

n = 199 n (%)

n = 717 n (%)

n = 506

n (%)

n = 65 n (%)

n = 146


230 (89.84)

61 (92.42)

2 1 58 169

(88.95) 131 15

23 Subjects on 2 drug regimens at index

9 (3.91) 0 0 0 0 9 6 2

1 Subjects on all other regimens at index

221 (96.09)

61 (100) 2 1 58 160

(94.67) 125 13

22 Change in CD4+ count from Baseline (first recorded CD4+ cell count), among subjects with CD4+ cell count available at Baseline

Mean (SD)

137.59 (296.69)

142.16 (247.9)

-90 (NA) 136 (NA)

147.83 (251.2)

135.66 (316.17)

163.07 (314.7

5)

211.44 (168.9)

6.62 (344.8

9) NA: Not applicable Treatment failure (treatment switch or discontinuation of a DTG-based regimen for any reason Subjects who switched off DTG before snapshot, no. (%)

81 (8.67)

9 (4.15) 1 (7.14) 1 (25) 7 (3.52) 72

(10.04) 52

(10.28) 7

(10.77) 13

(8.9)

10


27 (2.89)

8 (3.69) 0 (0) 0 (0) 8 (4.02) 19

(2.65) 3

(0.59) 3 (4.62)

13 (8.9)

Proportion of subjects who had a resistance test and number of subjects with new resistance mutation following initiation of DTG Resistance Mutations since DTG initiation, among subjects who switched and took DTG once daily No Post-Initiation Resistance Test

78 (98.73)

9 (100) 1 (100) 1 (100) 7 (100) 69

(98.57) 51

(100) 6 (100)

12 (92.31)


1 (1.27) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.43) 0 (0) 0 (0) 1

(7.69)

Resistance to Other

0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Resistance Mutations since DTG initiation, among subjects who switched and took DTG twice daily No Post-Initiation Resistance Test 1 (100) 0 0 0 0 1 (100) 0 1 (100) 0 No New Post-Initiation Resistances 0 (0) 0 0 0 0 0 (0) 0 0 (0) 0 Resistance to Other 0 (0) 0 0 0 0 0 (0) 0 0 (0) 0 Resistance Mutations since DTG initiation, among subjects who discontinued and took DTG once daily No Post-Initiation Resistance Test 25 (100) 8 (100) 0 0 8 (100) 17 (100) 3 (100) 3 (100)

11 (100)

No New Post-Initiation Resistances 0 (0) 0 (0) 0 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Resistance to Other 0 (0) 0 (0) 0 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Resistance Mutations since DTG initiation, among subjects who discontinued and took DTG twice daily No Post-Initiation Resistance Test 2 (100) 0 0 0 0 2 (100) 0 0 2 (100)

11

No New Post-Initiation Resistances 0 (0) 0 0 0 0 0 (0) 0 0 0 (0) Resistance to Other 0 (0) 0 0 0 0 0 (0) 0 0 0 (0) Virological failure Virological failure for any of the following reasons

42 (4.5) 18

(8.29) 2

(14.29) 0 (0)

16 (8.04)

24 (3.35)

9 (1.78)

5 (7.69) 10

(6.85)


1 (0.11) 1 (0.46) 0 (0) 0 (0) 1 (0.5) 0 (0) 0 (0) 0 (0) 0 (0)


14 (1.5) 2 (0.92) 0 (0) 0 (0) 2 (1.01) 12

(1.67) 3

(0.59) 1 (1.54)

8 (5.48)


19 (2.03)

8 (3.69) 1 (7.14) 0 (0) 7 (3.52) 11

(1.53) 6

(1.19) 3 (4.62)

2 (1.37)

12


1 (0.11) 0 (0) 0 (0) 0 (0) 0 (0) 1 (0.14) 0 (0) 1 (1.54) 0 (0)


7 (0.75) 7 (3.23) 1 (7.14) 0 (0) 6 (3.02) 0 (0) 0 (0) 0 (0) 0 (0)


0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)


Missing 26

(32.1) 2

(22.22) 0 (0) 0 (0)

2 (28.57)

24 (33.33)

18 (34.62)

1 (14.29)

5 (38.46)

Cost Reduction

12 (14.81)

0 (0) 0 (0) 0 (0) 0 (0) 12

(16.67) 10

(19.23) 1

(14.29) 1

(7.69) Simplification

4 (4.94) 1

(11.11) 0 (0) 1 (100) 0 (0) 3 (4.17)

1 (1.92)

0 (0) 2

(15.38) Clinician's decision

13 (16.05)

3 (33.33)

0 (0) 0 (0) 3

(42.86) 10

(13.89) 8

(15.38) 1

(14.29) 1

(7.69) subject Related

7 (8.64) 1

(11.11) 1 (100) 0 (0) 0 (0) 6 (8.33)

4 (7.69)

0 (0) 2

(15.38)

Renal 1 (1.23)

1 (11.11)

0 (0) 0 (0) 1

(14.29) 0 (0) 0 (0) 0 (0) 0 (0)

Gastrointestinal

2 (2.47) 0 (0) 0 (0) 0 (0) 0 (0) 2 (2.78) 2

(3.85) 0 (0) 0 (0)

Liver 1 (1.23) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.39)

1 (1.92)

0 (0) 0 (0)

CNS 1 (1.23) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.39) 0 (0) 0 (0)

1 (7.69)

Skin rash 2 (2.47) 0 (0) 0 (0) 0 (0) 0 (0) 2 (2.78)

2 (3.85)

0 (0) 0 (0)

Abdominal hypertrophy

0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Osteopaenia

1 (1.23) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.39) 1

(1.92) 0 (0) 0 (0)

Fatigue 1 (1.23) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.39) 0 (0)

1 (14.29)

0 (0)

Adverse Reaction

1 (1.23) 1

(11.11) 0 (0) 0 (0)

1 (14.29)

0 (0) 0 (0) 0 (0) 0 (0)

13


0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

CD4 and VL failure

2 (2.47) 0 (0) 0 (0) 0 (0) 0 (0) 2 (2.78) 2

(3.85) 0 (0) 0 (0)

Viral Failure 1 (1.23) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.39) 0 (0)

1 (14.29)

0 (0)

CD4 Failure 1 (1.23) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.39) 0 (0)

1 (14.29)

0 (0)

Resistance 1 (1.23) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.39)

1 (1.92)

0 (0) 0 (0)

Drug 1 (1.23) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.39) 0 (0)

1 (14.29)

0 (0)

Other 3 (3.7) 0 (0) 0 (0) 0 (0) 0 (0) 3 (4.17)

2 (3.85)

0 (0) 1

(7.69) CNS: Central nervous system Reason for discontinuation (among all subjects who discontinued)

Missing 14

(51.85) 4 (50) 0 0 4 (50)

10 (52.63)

2 (66.67)

2 (66.67)

6 (46.15)

Cost Reduction

0 (0) 0 (0) 0 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Simplification

1 (3.7) 1 (12.5) 0 0 1 (12.5) 0 (0) 0 (0) 0 (0) 0 (0)


5 (18.52)

0 (0) 0 0 0 (0) 5

(26.32) 0 (0) 0 (0)

5 (38.46)

CD4 and VL failure

1 (3.7) 1 (12.5) 0 0 1 (12.5) 0 (0) 0 (0) 0 (0) 0 (0)


0 (0) 0 (0) 0 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Other Reason given

6 (22.22)

2 (25) 0 0 2 (25) 4

(21.05) 1

(33.33) 1

(33.33) 2

(15.38)


Covariate

Overall TN TE

All TN

Subjects

Undetectable

at index

Suppressed at index

Unsuppressed

at index

All TE Subject

s

Undetectabl

e at index

Suppressed at index

Unsuppresse

d at index

n = 934 n (%)

n = 217 n (%)

n = 14 n (%)

n = 4 n (%)

n = 199 n (%)

n = 717 n (%)

n = 506

n (%)

n = 65 n (%)

n = 146


112 (91.06)

21 (95.45)

3 0 18 91

(91.09) 78 4 9


5 (4.46) 0 0 0 0 5 (5.49) 5 0 0

14


107 (95.54)

21 (100) 3 0 18 86

(94.51) 73 4 9

Change in CD4+ count from Baseline (first recorded CD4+ cell count), among subjects with CD4+ cell count available at Baseline

Mean (SD)

168.97 (333.47)

64.83 (284.91)

-26.5 (71.42)

- 83.1

(310.52) 187.35

(339.86)

209.75 (289.77

)

400.2 (335.81)

-15.27 (479.71)

Treatment failure (treatment switch or discontinuation of a DTG-based regimen for any reason Subjects who switched off DTG before snapshot, no. (%)

91 (9.74)

14 (6.45)

1 (7.14) 1 (25) 12 (6.03)

77 (10.74)

57 (11.26)

7 (10.77) 13 (8.9)


31 (3.35)

8 (3.77) 0 (0) 0 (0) 8 (4.12) 23

(3.23) 4 (0.8) 4 (6.15)

15 (10.2

7)


78 (98.73)

9 (100) 1 (100) 1 (100) 7 (100) 69

(98.57) 51 (100) 6 (100)

12 (92.3

1)


1 (1.27) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.43) 0 (0) 0 (0) 1

(7.69)

Resistance to Other

0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)


1 (100) 0 0 0 0 1 (100) 0 1 (100) 0

15


0 (0) 0 0 0 0 0 (0) 0 0 (0) 0

Resistance to Other

0 (0) 0 0 0 0 0 (0) 0 0 (0) 0


28 (100) 8 (100) 0 0 8 (100) 20 (100) 3 (100) 4 (100) 13

(100)


0 (0) 0 (0) 0 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Resistance to Other

0 (0) 0 (0) 0 0 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Resistance Mutations since DTG initiation, among subjects who discontinued and took DTG twice daily No Post-Initiation Resistance Test

3 (100) 0 0 0 0 3 (100) 1 (100) 0 2

(100)


0 (0) 0 0 0 0 0 (0) 0 (0) 0 0 (0)

Resistance to Other

0 (0) 0 0 0 0 0 (0) 0 (0) 0 0 (0)


57 (6.1) 22

(10.14) 2

(14.29) 0 (0)

20 (10.05)

35 (4.88)

12 (2.37)

6 (9.23) 17

(11.64)

16


1 (0.11) 1 (0.46) 0 (0) 0 (0) 1 (0.5) 0 (0) 0 (0) 0 (0) 0 (0)


21 (2.25)

4 (1.84) 0 (0) 0 (0) 4 (2.01) 17

(2.37) 6 (1.19) 1 (1.54)

10 (6.85)


27 (2.89)

10 (4.61)

1 (7.14) 0 (0) 9 (4.52) 17

(2.37) 6 (1.19) 4 (6.15)

7 (4.79)


1 (0.11) 0 (0) 0 (0) 0 (0) 0 (0) 1 (0.14) 0 (0) 1 (1.54) 0 (0)


7 (0.75) 7 (3.23) 1 (7.14) 0 (0) 6 (3.02) 0 (0) 0 (0) 0 (0) 0 (0)

17


0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Reason for switch (among all subjects who switched) recorded by clinician in Climate Missing 27

(29.67) 2

(14.29) 0 (0) 0 (0) 2

(16.67) 25

(32.47) 19

(33.33) 1

(14.29) 5

(38.46)

Cost Reduction

13 (14.29)

0 (0) 0 (0) 0 (0) 0 (0) 13 (16.88)

11 (19.3)

1 (14.29)

1 (7.69)

Simplification

4 (4.4) 1 (7.14) 0 (0) 1 (100) 0 (0) 3 (3.9) 1 (1.75) 0 (0) 2 (15.3

8) Clinician’s decision

15 (16.48)

5 (35.71)

0 (0) 0 (0) 5 (41.67)

10 (12.99)

8 (14.04)

1 (14.29)

1 (7.69)

Subject Related

7 (7.69) 1 (7.14) 1 (100) 0 (0) 0 (0) 6 (7.79) 4 (7.02) 0 (0) 2 (15.3

8) Renal 2 (2.2) 2

(14.29) 0 (0) 0 (0) 2

(16.67) 0 (0) 0 (0) 0 (0) 0 (0)

Gastrointestinal

4 (4.4) 1 (7.14) 0 (0) 0 (0) 1 (8.33) 3 (3.9) 3 (5.26) 0 (0) 0 (0)

Liver 1 (1.1) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.3) 1 (1.75) 0 (0) 0 (0) CNS 2 (2.2) 0 (0) 0 (0) 0 (0) 0 (0) 2 (2.6) 1 (1.75) 0 (0) 1

(7.69) Skin rash 2 (2.2) 0 (0) 0 (0) 0 (0) 0 (0) 2 (2.6) 2 (3.51) 0 (0) 0 (0) Abdominal hypertrophy

0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Osteopaenia

1 (1.1) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.3) 1 (1.75) 0 (0) 0 (0)

Fatigue 2 (2.2) 1 (7.14) 0 (0) 0 (0) 1 (8.33) 1 (1.3) 0 (0) 1 (14.29)

0 (0)

Adverse Reaction

1 (1.1) 1 (7.14) 0 (0) 0 (0) 1 (8.33) 0 (0) 0 (0) 0 (0) 0 (0)


0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

CD4 and VL failure

3 (3.3) 0 (0) 0 (0) 0 (0) 0 (0) 3 (3.9) 3 (5.26) 0 (0) 0 (0)

Viral Failure

1 (1.1) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.3) 0 (0) 1 (14.29)

0 (0)

CD4 Failure

1 (1.1) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.3) 0 (0) 1 (14.29)

0 (0)

Resistance 1 (1.1) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.3) 1 (1.75) 0 (0) 0 (0) Drug 1 (1.1) 0 (0) 0 (0) 0 (0) 0 (0) 1 (1.3) 0 (0) 1

(14.29) 0 (0)

Other 3 (3.3) 0 (0) 0 (0) 0 (0) 0 (0) 3 (3.9) 2 (3.51) 0 (0) 1 (7.69)

18

Reason for discontinuation (among all subjects who discontinued)

Missing 14

(45.16) 4 (50) 0 (NA) 0 (NA) 4 (50)

10 (43.48)

2 (50) 2 (50) 6 (40)

Cost Reduction

0 (0) 0 (0) 0 (NA) 0 (NA) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Simplification

1 (3.23) 1 (12.5) 0 (NA) 0 (NA) 1 (12.5) 0 (0) 0 (0) 0 (0) 0 (0)

Subject’s own choice

5 (16.13)

0 (0) 0 (NA) 0 (NA) 0 (0) 5

(21.74) 0 (0) 0 (0)

5 (33.3

3) CD4 and VL failure

3 (9.68) 1 (12.5) 0 (NA) 0 (NA) 1 (12.5) 2 (8.7) 0 (0) 1 (25) 1

(6.67) Clinician’s decision

0 (0) 0 (0) 0 (NA) 0 (NA) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Other Reason given

8 (25.81)

2 (25) 0 (NA) 0 (NA) 2 (25) 6

(26.09) 2 (50) 1 (25) 3 (20)

Clinical characteristics at last measurement Covariate Overall TN TE

All TN Subject

s

Undetectable

at index

Suppressed at index

Unsuppressed

at index

All TE Subject

s

Undetectable

at index

Suppressed at index

Unsuppressed at

index

n = 667 n (%)

n = 178 n (%)

n = 12 n (%)

n = 2 n (%)

n = 164 n (%)

n = 489 n (%)

n = 329 n (%)

n = 45 n (%)

n = 115


478 (82.99)

124 (77.5)

8 (66.67)

1 (100) 115

(78.23) 354

(85.1) 262

(90.03) 29

(80.56) 63

(70.79)


14 (2.93)

0 (0) 0 (0) 0 (0) 0 (0) 14

(3.95) 7 (2.67) 2 (6.9)

5 (7.94)


464 (97.07)

124 (100)

8 (100) 1 (100) 115

(100) 340

(96.05) 255

(97.33) 27

(93.1) 58

(92.06)


57 (96.61)

10 (100) 0 (NA) 1 (100) 9 (100) 47

(95.92) 33 (100) 4 (80)

10 (90.91)

19


2 (3.39) 0 (0) 0 (NA) 0 (0) 0 (0) 2 (4.08) 0 (0) 1 (20) 1

(9.09)

Resistance to Other

0 (0) 0 (0) 0 (NA) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)


0 (NA) 0 (NA) 0 (NA) 0 (NA) 0 (NA) 0 (NA) 0 (NA) 0 (NA) 0 (NA)



Resistance to Other



25 (89.29)

8 (100) 0 (NA) 0 (NA) 8 (100) 17 (85) 3 (100) 4 (100) 10

(76.92)


2 (7.14) 0 (0) 0 (NA) 0 (NA) 0 (0) 2 (10) 0 (0) 0 (0) 2

(15.38)

Resistance to Other

1 (3.57) 0 (0) 0 (NA) 0 (NA) 0 (0) 1 (5) 0 (0) 0 (0) 1

(7.69) Resistance Mutations since DTG initiation, among subjects who discontinued and took DTG once daily No Post-Initiation Resistance Test

3 (100) 0 (NA) 0 (NA) 0 (NA) 0 (NA) 3 (100) 1 (100) 0 (NA) 2 (100)


0 (0) 0 (NA) 0 (NA) 0 (NA) 0 (NA) 0 (0) 0 (0) 0 (NA) 0 (0)

Resistance to Other

0 (0) 0 (NA) 0 (NA) 0 (NA) 0 (NA) 0 (0) 0 (0) 0 (NA) 0 (0)


45 (6.75)

19 (10.67)

1 (8.33) 0 (0) 18

(10.98) 26

(5.32) 7 (2.13)

5 (11.11)

14 (12.17)

20


2 (0.3) 1 (0.56) 0 (0) 0 (0) 1 (0.61) 1 (0.2) 0 (0) 0 (0) 1 (0.87)


16 (2.4) 4 (2.25) 0 (0) 0 (0) 4 (2.44) 12

(2.45) 4 (1.22) 1 (2.22) 7 (6.09)


21 (3.15)

8 (4.49) 0 (0) 0 (0) 8 (4.88) 13

(2.66) 3 (0.91) 4 (8.89) 6 (5.22)


0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

21


6 (0.9) 6 (3.37) 1 (8.33) 0 (0) 5 (3.05) 0 (0) 0 (0) 0 (0) 0 (0)


0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)


Missing 17

(28.33) 1 (10) 0 (NA) 0 (0)

1 (11.11)

16 (32) 10

(29.41) 1 (20)

5 (45.45)

Cost Reduction

6 (10) 0 (0) 0 (NA) 0 (0) 0 (0) 6 (12) 5

(14.71) 1 (20) 0 (0)

Simplification

4 (6.67) 1 (10) 0 (NA) 1 (100) 0 (0) 3 (6) 1 (2.94) 0 (0) 2

(18.18) Clinician's decision

11 (18.33)

5 (50) 0 (NA) 0 (0) 5

(55.56) 6 (12)

5 (14.71)

0 (0) 1 (9.09)

Subject Related

3 (5) 0 (0) 0 (NA) 0 (0) 0 (0) 3 (6) 2 (5.88) 0 (0) 1 (9.09)

Renal 0 (0) 0 (0) 0 (NA) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) Gastrointestinal

4 (6.67) 1 (10) 0 (NA) 0 (0) 1

(11.11) 3 (6) 3 (8.82) 0 (0) 0 (0)

Liver 1 (1.67) 0 (0) 0 (NA) 0 (0) 0 (0) 1 (2) 1 (2.94) 0 (0) 0 (0) CNS 2 (3.33) 0 (0) 0 (NA) 0 (0) 0 (0) 2 (4) 1 (2.94) 0 (0) 1 (9.09) Skin rash 2 (3.33) 0 (0) 0 (NA) 0 (0) 0 (0) 2 (4) 2 (5.88) 0 (0) 0 (0) Abdominal hypertrophy

0 (0) 0 (0) 0 (NA) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Osteopaenia

1 (1.67) 0 (0) 0 (NA) 0 (0) 0 (0) 1 (2) 1 (2.94) 0 (0) 0 (0)

Fatigue 2 (3.33) 1 (10) 0 (NA) 0 (0)

1 (11.11)

1 (2) 0 (0) 1 (20) 0 (0)

Adverse Reaction

1 (1.67) 1 (10) 0 (NA) 0 (0) 1

(11.11) 0 (0) 0 (0) 0 (0) 0 (0)


0 (0) 0 (0) 0 (NA) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

CD4 and VL failure

1 (1.67) 0 (0) 0 (NA) 0 (0) 0 (0) 1 (2) 1 (2.94) 0 (0) 0 (0)

Viral Failure

1 (1.67) 0 (0) 0 (NA) 0 (0) 0 (0) 1 (2) 0 (0) 0 (0) 1 (9.09)

22

CD4 Failure

1 (1.67) 0 (0) 0 (NA) 0 (0) 0 (0) 1 (2) 0 (0) 1 (20) 0 (0)

Resistance

0 (0) 0 (0) 0 (NA) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Drug 1 (1.67) 0 (0) 0 (NA) 0 (0) 0 (0) 1 (2) 0 (0) 1 (20) 0 (0) Other 2 (3.33) 0 (0) 0 (NA) 0 (0) 0 (0) 2 (4) 2 (5.88) 0 (0) 0 (0) Reason for discontinuation (among all subjects who discontinued)

Missing 14

(45.16) 4 (50) 0 (NA) 0 (NA) 4 (50)

10 (43.48)

2 (50) 2 (50) 6 (40)

Cost Reduction

0 (0) 0 (0) 0 (NA) 0 (NA) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Simplification

1 (3.23) 1 (12.5) 0 (NA) 0 (NA) 1 (12.5) 0 (0) 0 (0) 0 (0) 0 (0)


5 (16.13)

0 (0) 0 (NA) 0 (NA) 0 (0) 5

(21.74) 0 (0) 0 (0)

5 (33.33)

CD4 and VL failure

3 (9.68) 1 (12.5) 0 (NA) 0 (NA) 1 (12.5) 2 (8.7) 0 (0) 1 (25) 1 (6.67)


0 (0) 0 (0) 0 (NA) 0 (NA) 0 (0) 0 (0) 0 (0) 0 (0) 0 ( 0)

Other Reason given

8 (25.81)

2 (25) 0 (NA) 0 (NA) 2 (25) 6

(26.09) 2 (50) 1 (25) 3 (20)

Conclusion: This real-world analysis supports study findings. The use of comedications frequently increased with age which also increased the risk of DDIs. When compared to DTG, most regimens were associated with an increased risk of red/amber DDIs. Darunavir+2NRTIs (ARV treatment regimen) resulted in the most frequent red interactions. DTG-based regimens were effective for both TN and TE subjects and resulted in no emergent resistance to integrase inhibitors. The virological failure, switch, discontinuation and adverse events were infrequently recorded.

exclusion criteria - amazon s3 · 2019-10-04 · subjects aged >=18 years of age at index date....

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