european hiv clinical forum: hiv integrase inhibitors -...

Reduced drug regimens - What are theData?

Dr. Jose R Arribas

@jrarribas

European HIV Clinical Forum: HIV Integrase Inhibitors - 2018

Reduced drug regimens - What are theData (naïve)?

Dr. Jose R Arribas

@jrarribas

European HIV Clinical Forum: HIV Integrase Inhibitors - 2018

3

Preferred ART in guidelines (naïve, triple)

Reduced Drug Regimens

EACS(2017)1

DHHS (2018)2,3

IAS–USA(2018)4

GeSIDA(2018)5

WHO (2018)6

NRTIbackbone

TAF/FTCTDF/FTC

ABC/3TC*

TAF/FTCTDF/FTC

ABC/3TC*

TAF/FTCABC/3TC*

TAF/FTCABC/3TC

2 NRTIs†

NNRTI RPV* – – – -

INSTI DTGRALEVG

BICRAL

DTG EVG/c

DTGBIC

DTGRAL

DTG‡

PI DRV/c or /r – – – –

*Use recommended only if baseline viral load

4

Preferred ART in GESIDA Guidelines

• Applicable to the majority of patients

• In RCT superior vs control

• In RCT non-inferior but have a superior tolerance, toxicity or interaction profile

• 88-90% with < 50 copies/mL at week 48 by FDA snapshot

•

PAST

Reduced Drug Regimens 5

6

Simplified drug regimens in ART-naïve populations


3TC, lamivudine; ART, antiretroviral therapy; ATV atazanavir; bPI, boosted protease inhibitor; CCR5, C-C chemokine receptor type 5; DRV, darunavir; EFV, efavirenz; F, emtricitabine; INSTI, integrase strand transfer inhibitor; LPV, lopinavir; NNRTI, non-nucleoside reverse-transcriptase inhibitors; NTRI, nucleotide reverse transcriptase inhibitors; r, ritonavir; RAL, raltegravir; TDF tenofovir disoproxil fumarate; ZDV, zidovudine.

bPI

bPI + NNRTI2008

2009

2010 2012

2013

2014

2015

2016

2011

MONARK:2

• LPV/r • LPV/r + ZDV/3TC

ACTG 5142:1

• LPV/r + EFV• LPV/r + 2 NRTIs

ACTG 5262:4

• DRV/r + RAL

PROGRESS:7

• LPV/r + RAL • LPV/r + F/TDF

SPARTAN:5

• ATV/r + RAL• ATV/r + F/TDF

RADAR:8

• DRV/r + RAL• DRV/r + F/TDF

NEAT 001:9


bPI + INSTI

bPI + 2 NRTIs

P04875:3

• ATV/r + VCV• ATV/r + F/TDF

A4001078:6

• ATV/r + MVC • ATV/r + F/TDF

MODERN:11

• DRV/r + MVC • DRV/r + F/TDF

bPI + CCR5I

GARDEL10

• LPV/r + 3TC • LPV/r + 2 NRTIs

bPI + NRTI

Source: 1. Riddler SA et al. N Engl J Med 2008;358:2095–106;2. Delfraissy JF et al. AIDS 2008;22(3):385–93;3. Dunkle LM et al. ICAAC 2010. Abstract #H-938a; 4. Taiwo B et al. AIDS 2011;25(17):2113–22;5. Kozal MJ et al. HIV Clin Trials 2012;13(3):119–30;6. Mills A et al. J Acquir Immune Defic Syndr 2013;62(2):164–70; 7. Reynes J et al. HIV Clin Trials 2011;12:255–67;8. Bedimo RJ et al. PLoS ONE 2014;9(8):e106221;9. Raffi F et al. Lancet 2014;84(9958):1942–51; 10. Cahn P et al. Lancet Infect Dis 2014;14(7):572–80; 11. Stellbrink HJ et al. AIDS 2016;30(8):1229–38.

7

NEAT 001 study: Primary endpoint* at week 96 by baselinecharacteristics


*Composite primary endpoint: change to randomised treatment before week 32 because of insufficient virological response, no virological response by week 32, HIV-1 RNA concentration 50 copies/mL or higher at any time after week 32; death from any cause; any new or recurrent AIDS event; or any serious non-AIDS event.

CD4, cluster of differentiation 4; CI, confidence interval; DRV, darunavir; F, emtricitabine; ITT, intention to treat; r, ritonavir; RAL, raltegravir; RNA, ribonucleic acid; TDF tenofovir disoproxil fumarate.

Source: Raffi F et al. Lancet 2014;384(9958):1942–51.

Overall analysis: DRV/r + RAL non-inferior to F/TDF + DRV/r

NDRV/r + RAL

(%)F/TDF + DRV/r (%)

Adjusted difference between treatment arms (%, 95% CI)

ITT analysis set 805 17.8 13.8 4.0 (-0.8 to 8.8)

Baseline HIV-1 RNA (Interaction test p=0.10)

8

NEAT 001 study: Emergent resistance with DRV/r + RAL


Resistance mutations in the DRV/r + RAL arm

Patient

Genotypic testing

Time VL (copies/mL) RT PROT IN Subsequent regimen VL at W96 (copies/mL)Suppressed before

resistance test

1 W47 247 L76V DRV/r + RAL

9




bPI

bPI + NNRTI2008

2009

2010 2012

2013

2014

2015

2016

2011

MONARK:2

• LPV/r • LPV/r + ZDV/3TC

ACTG 5142:1

• LPV/r + EFV• LPV/r + 2 NRTIs

ACTG 5262:4

• DRV/r + RAL

PROGRESS:7

• LPV/r + RAL • LPV/r + F/TDF

SPARTAN:5

• ATV/r + RAL• ATV/r + F/TDF

RADAR:8


NEAT 001:9


bPI + INSTI

bPI + 2 NRTIs

P04875:3

• ATV/r + VCV• ATV/r + F/TDF

A4001078:6

• ATV/r + MVC • ATV/r + F/TDF

MODERN:11

• DRV/r + MVC • DRV/r + F/TDF

bPI + CCR5I

GARDEL10

• LPV/r + 3TC • LPV/r + 2 NRTIs

bPI + NRTI

Source:1. Riddler SA et al. N Engl J Med 2008;358:2095–106; 2. Delfraissy JF et al. AIDS 2008;22(3):385–93; 3. Dunkle LM et al. ICAAC 2010. Abstract #H-938a; 4. Taiwo B et al. AIDS 2011;25(17):2113–22; 5. Kozal MJ et al. HIV Clin Trials 2012;13(3):119–30; 6. Mills A et al. J Acquir Immune Defic Syndr 2013;62(2):164–70; 7. Reynes J et al. HIV Clin Trials 2011;12:255–67; 8. Bedimo RJ et al. PLoS ONE 2014;9(8):e106221; 9. Raffi F et al. Lancet 2014;84(9958):1942–51; 10. Cahn P et al. Lancet Infect Dis 2014;14(7):572–80; 11. Stellbrink HJ et al. AIDS 2016;30(8):1229–38.

10

MODERN study: Primary endpoint – proportion of participantswith HIV-1 RNA less than 50 copies/mL at week 48


HIV-1 RNA

11

MODERN study: Week 48 virologic response by baseline characteristics

Reduced Drug RegimensSource: Stellbrink HJ et al. AIDS 2016;30(8):1229–38.

Proportion of subjects with HIV-1 RNA 350–500 cells/µL

CD4 200–350 cells/µL

CD4

12



bPI

bPI + NNRTI2008

2009

2010 2012

2013

2014

2015

2016

2011

MONARK:2

• LPV/r

• LPV/r + ZDV/3TC

ACTG 5142:1

• LPV/r + EFV

• LPV/r + 2 NRTIs

ACTG 5262:4

• DRV/r + RAL

PROGRESS:7

• LPV/r + RAL

• LPV/r + F/TDF

SPARTAN:5

• ATV/r + RAL

• ATV/r + F/TDF

RADAR:8

• DRV/r + RAL

• DRV/r + F/TDF

NEAT 001:9

• DRV/r + RAL

• DRV/r + F/TDF

bPI + INSTI

bPI + 2 NRTIs

P04875:3

• ATV/r + VCV

• ATV/r + F/TDF

A4001078:6

• ATV/r + MVC

• ATV/r + F/TDF

MODERN:11

• DRV/r + MVC

• DRV/r + F/TDF

bPI + CCR5I

GARDEL10

• LPV/r + 3TC

• LPV/r + 2 NRTIs

bPI + NRTI


Source: 1. Riddler SA et al. N Engl J Med 2008;358:2095–106; 2. Delfraissy JF et al. AIDS 2008;22(3):385–93; 3. Dunkle LM et al. ICAAC 2010. Abstract #H-938a; 4. Taiwo B et al. AIDS 2011;25(17):2113–22; 5. Kozal MJ et al. HIV Clin Trials 2012;13(3):119–30; 6. Mills A et al. J Acquir Immune Defic Syndr 2013;62(2):164–70; 7. Reynes J et al. HIV Clin Trials 2011;12:255–67; 8. Bedimo RJ et al. PLoS ONE 2014;9(8):e106221; 9. Raffi F et al. Lancet 2014;84(9958):1942–51; 10. Cahn P et al. Lancet Infect Dis 2014;14(7):572–80; 11. Stellbrink HJ et al. AIDS 2016;30(8):1229–38.

13



Viral load

14

ANDES Study: Proportion with HIV-RNA < 50 Copies/mL and Safety

Source: Figueroa M, et al. 25th CROI; Boston, MA; March 4-7, 2018. Abst. 489

GlobalTriple

TherapyDouble Therapy Difference

Primary Outcome: VL100,00 c/ml (n=35)

32 (91%) 12 (92%)20 (91%)

-1.4% (-17.2; 14.4%)

Observed (n=140) 136 (99%) 66 (99%) 70 (100%) -1.5% (-0.9; 3.9%)

Adverse Events

Rash 7% 8%

Gastrointestinal 14% 7%

Total Cholesterol(Change from BSL)

4% 19%; p:0.01

LDL-Cholesterol 6% 14%

Triglycerides 14% 25%


15

PADDLE: DTG + 3TC (NAÏVE)

Spurce: Cahn P, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. FARB0104LB.

# SCR BSL DAY 4 DAY 7 W.2 W.3 W.4 W.6 W.8 W.12 W.24 W.36 W.48

1 5.584 10.909 383 101 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

2 8.887 10.233 318 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

3 67.335 151.569 1.565 1.178 97 53 < 50 < 50 < 50 < 50 < 50 < 50 < 50

4 99.291 148.370 3.303 432 178 55 < 50 < 50 < 50 < 50 < 50 < 50 < 50

5 34.362 20.544 1.292 570 107 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

6 16.024 14.499 1.634 162 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

7 37.604 18.597 819 61 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

8 25.071 24.368 1.377 Not done 105 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

9 14.707 10.832 516 202 < 50 < 50 < 50 < 50 < 50 < 50 < 50 SAE

10 10.679 7.978 318 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

11 50.089 273.676 68.129 3.880 784 290 288 147 < 50 < 50 < 50 < 50 < 50

12 13.508 64.103 3.296 135 351 84 67 < 50 < 50 < 50 < 50 < 50 < 50

13 28.093 33.829 26.343 539 61 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

14 15.348 15.151 791 198 < 50 61 64 < 50 < 50 < 50 < 50 < 50 < 50

15 23.185 23.500 4.217 192 < 50 < 50 < 50 Not done < 50 < 50 < 50 < 50 < 50

16 11.377 3.910 97 143 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

17 39.100 25.828 1.970 460 52 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

18 60.771 73.069 2.174 692 156 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

19 82.803 106.320 2.902 897 168 76 < 50 < 50 < 50 < 50 < 50 PDVF

20 5.190 7.368 147 56 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

20 años ART

16

ACTG 5353: Study design


Phase II, single-arm, 52-week, study of DTG 50 mg + 3TC 300 mg in treatment-naïve participants

Primary objective

• To estimate the virologic success rate at week 24, defined as on-treatment VL 100,000 (n=83) c/mL

• Describe emergent integrase and RT resistance during virologic failure

• Evaluate safety and tolerability

• Explore impact of minority drug-resistant variants and drug exposure/adherence on observed outcomes

Treatment naive participantsVL ≥1000 and

17

ACTG 5353: Efficacy and Resistance

Reduced Drug RegimensSource: Taiwo B et al. IAS 2017. Paris, France. Oral #MOAB0107LB.

90

27

89

83

0

10

20

30

40

50

60

70

80

90

100

HIV-1 RNA < 50 c/mL

HIV-1 RNA≥50 c/mL

No virologicdata

Pro

po

rtio

n o

f p

arti

cip

ants

, %

≤100K c/mL (n=83)

>100K c/mL (n=37)

Baseline VL (c/mL)

HIV-1 RNA ≥50c/mL* (n=5)

Mutations

INSTI NRTI NNRTI

>100,000 3 - - -

≤100,000 1 R263R/K M184V -

≤100,000 1 - - V106I

Includes protocol defined virologic failures, n=3 (confirmed VL >400 c/mL at week 16 or 20 or confirmed VL >200 c/mL at/after week 24) and lack of virologic success, n=2 (VL ≥50 c/mL at week 24)

3TC, lamivudine; c, copies; DTG, dolutegravir; FDA, US Food and Drug Administration; INSTI, integrase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; VL, viral load.

PRESENT

Reduced Drug Regimens 18

19

GEMINI-1 and -2 Phase III Study Design: Identically designed, randomized, double-blind, parallel-group, multicenter, noninferiority studies

Source: Cahn et al. AIDS 2018; Amsterdam, the Netherlands. Slides TUAB0106LB

a−10% noninferiority margin for individual studies.

DTG + 3TC (N=716)

Day 1

Screening (28 d)

DTG + TDF/FTC (N=717)

DTG + 3TC

Week48

Primary endpoint at Week 48:

participants withHIV-1 RNA 100,000 c/mL) CD4+ cell count (≤200 cells/mm3 vs >200 cells/mm3).


20

Demographic and Baseline Characteristics for the Pooled GEMINI-1 and -2 Population

Source: Cahn et al. AIDS 2018; Amsterdam, the Netherlands. Slides TUAB0106LB.

a2% of participants in each arm had baseline HIV-1 RNA >500,000 c/mL and were included in the ITT-E analysis.

CharacteristicDTG + 3TC(N=716)

DTG + TDF/FTC(N=717)

Age, median (range), y≥50 y, n (%)

32.0 (18-72)65 (9)

33.0 (18-70)80 (11)

Female, n (%) 113 (16) 98 (14)

Race, n (%)African American/African heritageAsianWhiteOther

Ethnicity, n (%)Hispanic or LatinoNot Hispanic or Latino

99 (14)71 (10)

480 (67)66 (9)

215 (30)501 (70)

76 (11)72 (10)

497 (69)72 (10)

232 (32)485 (68)

HIV-1 RNA, median (range), log10 c/mL≤100,000>100,000a

4.43 (1.59-6.27)576 (80)140 (20)

4.46 (2.11-6.37)564 (79)153 (21)

CD4+ cell count, median (range), cells/mm3

>200≤200

427.0 (19-1399)653 (91)

63 (9)

438.0 (19-1497)662 (92)

55 (8)


21

Snapshot Outcomes at Week 48 for GEMINI-1


-10 -8 -6 -4 -2 0 2 4 6 8 10

Virologic outcome Adjusted treatment difference (95% CI)a

Percentage-point difference

DTG + TDF/FTC

-6.7 1.5

GEMINI-1 -2.6

DTG + TDF/FTC DTG + 3TC

90

4 6

93

26

0

20

40

60

80

100

Virologicsuccess

Virologicnonresponse

No virologicdata

HIV

-1 R

NA

<5

0 c

/mL,

%

GEMINI-1 DTG + 3TC (N=356) DTG + TDF/FTC (N=358)

aBased on Cochran-Mantel-Haenszel stratified analysis adjusting for the following baseline stratification factors: plasma HIV -1 RNA (≤100,000 c/mL vs >100,000 c/mL) and CD4+ cell count (≤200 cells/mm3 vs >200 cells/mm3).


22

Snapshot Outcomes at Week 48 for GEMINI-1 and -2


-10 -8 -6 -4 -2 0 2 4 6 8 10



DTG + 3TC is non-inferior to DTG + TDF/FTC with respect to proportion 100,000 c/mL) and CD4+ cell count (≤200 cells/mm3 vs >200 cells/mm3).


23

Snapshot Analysis by Visit: Pooled ITT-E Population


0

70

85 89

90

93

91 93

72

87 89

88

93

9091

-20

0

20

40

60

80

100

-4 0 4 8 12 16 20 24 28 32 36 40 44 48

HIV

-1 R

NA

<5

0 c

/mL,

%a

Study visit

DTG + 3TC (n=716)

DTG + TDF/FTC (n=717)

aCalculated from a repeated measures model adjusting for study, treatment, visit (repeated factor), baseline plasma HIV -1 RNA, baseline CD4+ cell count, treatment and visit interaction, and baseline CD4+ cell count and visit interaction.


24

Snapshot Analysis by Visit: Pooled ITT-E Population


0

70

85 89

90

93

91 93

72

87 89

88

93

9091

-20

0

20

40

60

80

100

-4 0 4 8 12 16 20 24 28 32 36 40 44 48

HIV

-1 R

NA

<5

0 c

/mL,

%a

Study visit

DTG + 3TC (n=716)


aCalculated from a repeated measures model adjusting for study, treatment, visit (repeated factor), baseline plasma HIV -1 RNA, baseline CD4+ cell count, treatment and visit interaction, and baseline CD4+ cell count and visit interaction.

CD4+ cell count (cells/mm3)

Adjusted mean change from baseline at Week 48b

DTG + 3TC 224

DTG + TDF/FTC 218


25

Pooled Snapshot Outcomes at Week 48: ITT-E Population




-10 -8 -6 -4 -2 0 2 4 6 8 10

-4.4 1.1

-1.7


ITT-E

91

36

93

25

0

20

40

60

80

100

Virologicsuccess

Virologicnonresponse

No virologicdata

HIV

-1 R

NA

<5

0 c

/mL,

%

ITT-E DTG + 3TC (N=716) DTG + TDF/FTC (N=717)

aBased on Cochran-Mantel-Haenszel stratified analysis adjusting for the following baseline stratification factors: plasma HIV-1 RNA (≤100,000 c/mL vs >100,000 c/mL), CD4+ cell count (≤200 cells/mm3 vs >200 cells/mm3), and study (GEMINI-1 vs GEMINI-2).


26

Pooled Snapshot Outcomes at Week 48: ITT-E and Per ProtocolPopulations


aBased on Cochran-Mantel-Haenszel stratified analysis adjusting for the following baseline stratification factors: plasma HIV-1 RNA (≤100,000 c/mL vs >100,000 c/mL), CD4+ cell count (≤200 cells/mm3 vs >200 cells/mm3), and study (GEMINI-1 vs GEMINI-2). bPP, per protocol: population consisted of participants in the ITT-E population except for significant protocol violators, which could potentially affect efficacy outcomes as determined by the medical monitor prior to database lock.



-10 -8 -6 -4 -2 0 2 4 6 8 10

-4.4 1.1

-1.7


DTG + 3TC is non-inferior to DTG + TDF/FTC with respect to proportion

27

Pooled Outcomes at Week 48 Stratified by Baseline HIV-1 RNA: ITT-E Analysis


91 9394 9392

79

90 93

0

20

40

60

80

100

HIV

-1 R

NA

<5

0 c

/mL

, %

ITT-E Analysis

2% of participants in each arm had baseline HIV-1 RNA >500,000 c/mL

DTG + 3TC DTG + TDF/FTC

>100,000≤100,000 >200 ≤200

Baseline HIV-1 RNA, c/mL

Baseline CD4+ cell count, cell/mm3

526

576

531

564

129

140

138

153

605

653

618

662

50

67

51

55


28

Pooled Outcomes at Week 48 Stratified by Baseline HIV-1 RNA and CD4+ Cell Count: ITT-E Analysis


91 9394 9392

79

90 93

0

20

40

60

80

100

HIV

-1 R

NA

<5

0 c

/mL

, %

ITT-E Analysis

2% of participants in each arm had baseline HIV-1 RNA >500,000 c/mL


>100,000≤100,000 >200 ≤200



526

576

531

564

129

140

138

153

605

653

618

662

50

67

51

55


29

Pooled Outcomes at Week 48 Stratified by Baseline HIV-1 RNA and CD4+ Cell Count: ITT-E and Pre-planned TRDF Analysis


98 9898 9899 9897 100

0

20

40

60

80

100

Wit

ho

ut

TRD

F, %

TRDF Analysis

566

576

>100,000≤100,000 >200 ≤200



91 9394 9392

79

90 93

0

20

40

60

80

100

HIV

-1 R

NA

<5

0 c

/mL,

%

ITT-E Analysis

• 2% of participants in each arm had baseline HIV-1 RNA >500,000 c/mL• Treatment related discontinuation = failure (TRDF) population accounts for confirmed virologic withdrawal (CVW), withdrawal

due to lack of efficacy, withdrawal due to treatment-related AE, and participants who met protocol-defined stopping criteria• DTG + 3TC CD4 50 in window, 3 of 4 re-

suppressed; 2 protocol violations, 1 withdrew consent, 1 withdrew to start HCV treatment


>100,000≤100,000 >200 ≤200



553

564

138

140

149

153

642

653

647

662

62

63

55

55

526

576

531

564

129

140

138

153

605

653

618

662

50

63

51

55


30

Confirmed Virologic Withdrawals Through Week 48: ITT-E Population


GEMINI 1 GEMINI 2 Pooled

Variable, n (%)

DTG + 3TC

(N=356)

DTG +

TDF/FTC

(N=358)

DTG + 3TC

(N=360)

DTG +

TDF/FTC

(N=359)

DTG + 3TC

(N=716)

DTG +

TDF/FTC

(N=717)

CVW 4 (1) 2 (

31

Adverse Events: Pooled ITT-E Population


n (%)

DTG + 3TC

(N=716)DTG + TDF/FTC

(N=717)

Any AE 543 (76) 579 (81)

AE occurring in ≥5% of participants in either groupHeadacheDiarrheaNasopharyngitisUpper respiratory tract infectionNauseaInsomniaPharyngitisBack pain

71 (10)68 (9)55 (8)56 (8)27 (4)27 (4)36 (5)35 (5)

75 (10)77 (11)78 (11)44 (6)53 (7)45 (6)32 (4)31 (4)

Drug-related AEGrade 2-4 AE occurring in ≥1% of participants

Headache

126 (18)42 (6)8 (1)

169 (24)47 (7)8 (1)

AE leading to withdrawal from the studyNeuropsychiatric AEs leading to withdrawal

15 (2)6 (

32

Adverse Events Leading to Withdrawal: Pooled ITT-E Population


n (%)

DTG + 3TC(N=716)

DTG + TDF/FTC(N=717)

Participants with AEs leading to withdrawal from the study 15 (2) 16 (2)

All events leading to withdrawal (participant may report >1 AE)Hepatitis AAlcoholic hepatitisAcute hepatitis CHepatoxicityDrug-induced liver injuryHepatitis CRenal impairmentCreatinine renal clearance decreasedGlomerular filtration rate decreasedAnxietyDepressionSuicide attemptSuicidal ideationInsomniaSleep disorderPsychotic disorderSubstance-induced psychotic disorderOverdoseAlcoholic psychosisAcute myocardial infarctionBurkitt’s lymphoma Non-Hodgkin’s lymphomaB-cell lymphomaPulmonary tuberculosisTuberculous pleurisyOsteoporosisRhabdomyolysis

2 (

33

Change in Renal Biomarkers at Week 48: Pooled ITT-E Population


6.3

10.4

-12.1

4.1

13.5

-15.5

-20

-15

-10

-5

0

5

10

15

Ad

jus

ted

me

an

ch

an

ge f

rom

ba

se

lin

ea

GFR fromcystatin C,

CKD-EPI (mL/min/1.73 m2)

GFR fromcreatinine,

CKD-EPI (mL/min/1.73 m2)

Creatinine(µmol/L)

aEstimated mean change from baseline at Week 48 in each arm calculated from ANCOVA model adjusting for: study, treatment, baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, and baseline biomarker value. Multiple imputed dataset (missing at random). bEstimated from geometric means for baseline and Week 48.

Plasma/Serum markers

-13.1

-7.4 -7.7

2.9

11.4

31.2

-20

-10

0

10

20

30

40

Ch

an

ge f

rom

ba

se

lin

e, %

b

Urine markers

Protein/Creatinine

(g/mol)

Retinol-bindingprotein/

Creatinine(µg/mmol)

Beta-2microglobulin/

Creatinine(mg/mmol)

DTG + 3TC (n=716) DTG + TDF/FTC (n=717)

*

*

*

*

*

*

*p

34

Change in Bone Markers at Week 48: Pooled ITT-E Population


1.220.60 0.40 0.14

4.07

6.17

13.10

0.330

5

10

15

Serum bone specificalkaline phosphatase

Serumosteocalcin

Serum procollagen 1N-terminal propeptide

Serum type 1 collagenC-telopeptide

Ad

jus

ted

me

an

ch

an

ge

fro

m

baseli

ne (

µg

/L)a

aEstimated mean change from baseline at Week 48 in each arm calculated from ANCOVA model adjusting for study, treatment, baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, BMI, smoking status, current vitamin D use, and baseline biomarker value. Multiple imputed dataset (missing at random).

DTG + 3TC (n=716)


*

*

*

*

*p

35

Change in Serum Lipids at Week 48: Pooled ITT-E Population


0

1

2

3

4

5

Ad

jus

ted

me

an

ch

an

ge

fro

m b

as

eli

ne

a

Total cholesterol(mmol/L)

LDL cholesterol (mmol/L)

Total cholesterol/HDL cholesterol

ratio

HDL cholesterol (mmol/L)

Triglycerides(mmol/L)

DTG + 3TC (n=716)


0.320.15

0.15

0.17

0.03

0.12

0.14

0.08

0.24

0.02

** **p

36

Here in Glasgow


37

Preferred ART in guidelines (naïve, triple)


EACS(2017)1

DHHS (2018)2,3

IAS–USA(2018)4

GeSIDA(2018)5

WHO (2018)6

NRTIbackbone

TAF/FTCTDF/FTC

ABC/3TC*

TAF/FTCTDF/FTC

ABC/3TC*

TAF/FTCABC/3TC*

TAF/FTCABC/3TC

2 NRTIs†

NNRTI RPV* – – – -

INSTI DTGRALEVG

BICRAL

DTG EVG/c

DTGBIC

DTGRAL

DTG‡

PI DRV/c or /r – – – –

*Use recommended only if baseline viral load

– It is an INSTI– No impact of high viral loads

european hiv clinical forum: hiv integrase inhibitors -...

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