non-inferior efficacy of dolutegravir (dtg) plus ... · •the requirement for lifelong art for hiv...

Non-Inferior Efficacy of Dolutegravir▼(DTG) plusLamivudine (3TC) vs DTG plus Tenofovir/Emtricitabine (TDF/FTC) Fixed-Dose Combination in Antiretroviral Treatment–Naive Adults with HIV-1 Infection

Week 48 Results from the GEMINI-1 & GEMINI-2 Studies

UK/DTG3TC /0019/18(1) November 2018

Prescribing information can be found at the end of this presentation

Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.

Why investigate a 2-drug regimen?

No one should take more medicine than they need

A 20-year old starting a 3-drug regimen (3DR) may be on therapy for nearly 6

decades, which translates to more that 60,000 doses of individual medications.1

Managing comorbidities, DDIs and potential long-term effects of treatment are

important considerations

1. The Antiretroviral Therapy Cohort Collaboration. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort

studies. Lancet HIV. 2017;4(8):e349-e356

2. Marcotullio S, et al. EACS 2017, poster PE25/9

ARV, antiretroviral; PLHIV, people living with HIV

The Positive Perspectives Survey highlighted that 72% (n=783/1085) of

PLHIV worry about the long-term impact of their medicines on their bodies2

The potential benefits associated with 2-drug regimens (2DRs) include

reduced ARV exposure and potential for toxicities, drug preservation for

future treatment options and increased treatment access

3DRs achieve viral suppression by targeting two different intracellular viral

replication processes; 2DRs can be expected to achieve the same as they also

target two distinct viral replication processes

• The requirement for lifelong ART for HIV infection has highlighted interest in

2DRs to minimize cumulative drug exposure1

• Lower ARV exposure may translate to less long-term drug toxicity

• The potency, safety and high resistance barrier of DTG make it an optimal core

agent for 2DRs

• The safety, tolerability and efficacy of 3TC make it a reliable partner for initial

HIV-1 treatment

• Previous pilot studies have evaluated DTG + 3TC as a complete 2DR in

treatment-naive participants

– PADDLE: 90% (18/20) had VL <50 c/mL at Week 482

– ACTG A5353: 90% (108/120) had VL <50 c/mL at Week 243

• DTG + 3TC was evaluated vs a 3-drug regimen (3DR) DTG + TDF/FTC for

treatment-naive patients with HIV-1 infection through 48 weeks

Introduction

1. Kelly et al. Drugs. 2016;76(5):523-531.

2. Cahn et al. J Int AIDS Soc. 2017;20(1):21678.

3. Taiwo et al. Clin Infect Dis. 2018;66(11):1689-1697.

ART, antiretroviral therapy

a−10% noninferiority margin for individual studies.

GEMINI-1 and -2 Phase III Study Design

Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.

DTG + 3TC (N=716)

Day

1

Screening

(28 d)

Identically designed, randomized, double-blind, parallel-group,

multicenter, noninferiority studies

DTG + TDF/FTC (N=717)

DTG + 3TC

Week

48

Primary endpoint

at Week 48:

participants with

HIV-1 RNA <50 c/mL

(ITT-E snapshot)a

Double-blind

phase

Open-label

phase

Continuation

phase

CountriesArgentina Australia Belgium

Canada France Germany

Italy Republic of Korea Mexico

Netherlands Peru Poland

Portugal Romania Russian Federation

South Africa Spain Switzerland

Taiwan United Kingdom United States

China

Week

144

Week

24

Week

96

• ART-naive adults

• VL 1000-500,000 c/mL

1:1

Eligibility criteria• ≤10 days of prior ART

• No evidence of pre-existing viral resistance

based on presence of any major resistance-

associated mutation

• No HBV infection or need for HCV therapy

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).

Demographic and Baseline Characteristics

for the Pooled GEMINI-1 and -2 Population

Characteristic

DTG + 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 heritage

Asian

White

Other

Ethnicity, n (%)

Hispanic or Latino

Not 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)

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


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

Snapshot Outcomes at Week 48for GEMINI-1

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).

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

<50

c/m

L, %

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


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

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


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



DTG + 3TC is non-inferior to DTG +

TDF/FTC with respect to proportion

<50 c/mL at Week 48 (snapshot, ITT-E

population) in both studies

DTG + TDF/FTC

-6.7 1.5

-4.3 2.9

GEMINI-1

GEMINI-2 -0.7

-2.6


90

4 6

93

26

93

25

94

2 4

0

20

40

60

80

100

Virologicsuccess


No virologicdata

HIV

-1 R

NA

<50

c/m

L, %




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

<50 c

/mL, %

a

Study visit (weeks)

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.


Pooled Snapshot Outcomes at Week 48: ITT-E Population


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).



-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


No virologicdata

HIV

-1 R

NA

<50

c/m

L, %

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


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


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

<50 c/mL at Week 48 (snapshot, ITT-E

population) in both studies

-1.3

-3.9 1.2

ITT-E

PP

91

36

93

25

93

25

94

14

0

20

40

60

80

100

Virologicsuccess


No virologicdata

HIV

-1 R

NA

<50

c/m

L, %

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

PPb DTG + 3TC (N=694) DTG + TDF/FTC (N=693)


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

91 9394 9392

79

9093

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


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

91 9394 9392

79

9093

0

20

40

60

80

100

HIV

-1 R

NA

<5

0 c

/mL

, %

ITT-E Analysis



>100,000≤100,000 >200 ≤200

Baseline HIV-1

RNA, c/mL

Baseline CD4+


526

576

531

564

129

140

138

153

605

653

618

662

50

63

51

55


98 9898 9899 9897 100

0

20

40

60

80

100

Wit

ho

ut

TR

DF,

%

TRDF Analysis

566

576

>100,000≤100,000 >200 ≤200

Baseline HIV-1

RNA, c/mL

Baseline CD4+


Pooled Outcomes at Week 48 Stratified by Baseline HIV-1 RNA

and CD4+ Cell Count: ITT-E and Pre-planned TRDF Analysis

91 9394 9392

79

9093

0

20

40

60

80

100

HIV

-1 R

NA

<5

0 c

/mL

, %

ITT-E Analysis


• 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 <200 Snapshot non-response: 1 CVW, 2 discontinued due to AE (TB, Chagas disease); 4 with VL >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

Baseline HIV-1

RNA, c/mL

Baseline CD4+


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


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 (<1) 2 (<1) 2 (<1) 6 (<1) 4 (<1)

Treatment-emergent

resistance

0 0 0 0 0 0

• Low rates of virologic withdrawals were observed at Week 48

• No treatment-emergent INSTI mutations or NRTI mutations were

observed among participants who met CVW (confirmed virologic

failure) criteria

Confirmed virologic withdrawal criteria is defined as a second and consecutive HIV-1 RNA value meeting virologic non-response or rebound. Virologic non-response is defined as either a decrease in

plasma HIV-1 RNA of less than 1 log10 c/mL by Week 12 with subsequent confirmation unless plasma HIV-1 RNA is <200 c/mL, or confirmed plasma HIV-1 RNA levels ≥200 c/mL on or after Week 24.

Virologic rebound is defined as confirmed rebound in plasma HIV-1 RNA levels to ≥200 c/mL after prior confirmed suppression to <200 c/mL.

.Adapted from : Cahn et al. The Lancet. Published online November 9, 2018 http://dx.doi.org/10.1016/S0140-6736(18)32462-0.

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 group

Headache

Diarrhea

Nasopharyngitis

Upper respiratory tract infection

Nausea

Insomnia

Pharyngitis

Back 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 AE

Grade 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 study

Neuropsychiatric AEs leading to withdrawal

15 (2)

6 (<1)

16 (2)

4 (<1)

Any serious AEa 50 (7) 55 (8)

a2 deaths (acute myocardial infarction, n=1; Burkitt’s lymphoma, n=1) in the GEMINI-2 study; both were in the DTG + 3TC group and were

considered unrelated to the study drug regimen.


Adverse Events Leading to Withdrawal:

Pooled ITT-E Population

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

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 (<1)1 (<1)1 (<1)1 (<1)

00

1 (<1)00

1 (<1)1 (<1)1 (<1)1 (<1)1 (<1)1 (<1)1 (<1)1 (<1)

00

1 (<1)1 (<1)

00

1 (<1)1 (<1)

00

1 (<1)1 (<1)1 (<1)

01 (<1)1 (<1)2 (<1)1 (<1)1 (<1)1 (<1)1 (<1)1 (<1)1 (<1)

0000

1 (<1)1 (<1)

00

1 (<1)1 (<1)

00

1 (<1)1 (<1)


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

eGFR from

cystatin C,

CKD-EPI

(mL/min/

1.73 m2)

eGFR from

creatinine,

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 mean ratio 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-binding

protein/

Creatinine

(µg/mmol)

Beta-2

microglobulin/

Creatinine

(mg/mmol)

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

*

*

*

*

*

*

*p<0.001a


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<0.001


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

0

1

2

3

4

5

Ad

jus

ted

me

an

va

lue

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<0.001

**

**

*

*

*p<0.05

aThe adjusted mean is the estimated mean change from baseline in each fasting lipid at Week 48 in each arm calculated from an ANCOVA model adjusting for the

following covariates/factors: study treatment, baseline plasma HIV-1 RNA, baseline CD4+ cell count, age and fasting lipids at baseline. Multiple imputed dataset

(missing at random). Absolute values based on summaries. Baseline values are represented by the main legend colors, with changes at Week 48 represented by

shaded areas (increases) or dashed lines (decreases).


• GEMINI-1 and GEMINI-2 results demonstrate non-inferior virologic efficacy for

the 2DR DTG + 3TC vs a 3DR DTG + TDF/FTC at Week 48

• Both DTG + 3TC and DTG + TDF/FTC were associated with low rates of

confirmed virologic withdrawals through Week 48

– No treatment-emergent INSTI or NRTI mutations were observed among participants

who met CVW criteria

• Overall safety and tolerability profile at Week 48 was comparable between the

2 regimens

– Fewer drug-related AEs with DTG + 3TC

– Statistically significant change in renal and bone biomarkers from baseline favours

DTG + 3TC vs DTG + TDF/FTC

• GEMINI-1 and GEMINI-2 data support DTG + 3TC as a 2DR for the treatment of

HIV-1 infection in treatment-naïve HBV-negative patients with viral loads up to

500,000 copies/mL

Conclusions

Prescribing Information

Tivicay▼ dolutegravir 10mg, 25mg and 50mg tablets See Summary of Product Characteristics before prescribing

Indication: HIV in >6 years and >15kg as part of combination therapy. Dosing: Adults & adolescents >40kg: 50mg once daily with or without food if no proven/ suspected integrase resistance. Children 6 to <12 years: dose according to bodyweight: 15-<20kg: 20mg once daily (2x10mg); 20-<30kg: 25mg once daily; 30-<40kg: 35mg once daily (1 x 25mg + 1 x 10mg); When co-administered with efavirenz, nevirapine, tipranavir/ritonavir, etravirine (without boosted PI), carbamazepine, oxcarbazepine, phenytoin, phenobarbital, St John’s Wort or rifampicin, Tivicay 50mg twice daily in adults/adolescents or the weight-based once daily dose twice daily in paediatric patients. Adults with proven or suspected integrase resistance: 50mg twice daily preferably with food. Limited data in paediatric patients with proven/suspected integrase resistance. Elderly: Limited data in 65+ yrs. Caution in severe hepatic impairment. Contraindications: Hypersensitivity to any ingredient. Co-administration with dofetilide. Warnings/precautions: Risk of hypersensitivity reactions. Discontinue dolutegravir and other suspect agents immediately if suspected. The two-drug regimen of dolutegravir and lamivudine is only suitable for the treatment of HIV-1 infection where there is no known or suspected resistance to the integrase inhibitor class, or to lamivudine. Risks of osteonecrosis, immune reactivation syndrome. Monitor LFTs in Hepatitis B/C co-infection and ensure

effective Hepatitis B therapy. Caution with metformin: monitor renal function and consider metformin dose adjustment. Use with etravirine requires boosted PI or increased dose of dolutegravir. Use with Mg/Al-containing antacids, calcium, multivitamins or iron requires dosage separation. Pregnancy/ lactation: Not recommended. Avoid breast-feeding. Side effects: See SmPC for full details. Headache, GI disturbance, insomnia, abnormal dreams, depression, anxiety, dizziness, rash, pruritus, fatigue, elevations of ALT, AST and CPK, arthralgia, myalgia, hypersensitivity, suicidal ideation or suicide attempt, acute hepatic failure. Basic NHS costs: £498.75 for 30 x 50mg tablets EU/1/13/892/001. £99.75 for 30 x 10mg tablets (EU/1/13/892/003). £249.38 for 30 x 25mg tablets (EU/1/13/892/005). MA holder: ViiV Healthcare BV, Huis terHeideweg 62, 3705 LZ Zeist, Netherlands. Further information available from Customer Contact Centre, GlaxoSmithKline UK Ltd, Stockley Park West, Uxbridge, Middlesex UB11 1BT.

Trade marks are owned by or licensed to the ViiV Healthcare group of companies.

Date of approval: November 2018. Zinc code: UK/DLG/0055/13(15)

Adverse events should be reported. For the UK, reporting forms and information can be found at www.mhra.gov.uk/yellowcard or

search for MHRA Yellowcard in the Google Play or Apple App store. Adverse events should also be reported to GlaxoSmithKline on

0800 221441.

Adverse events should be reported. For Ireland, adverse events should be reported directly to the HPRA; Freepost, PharmacovigilanceSection, Health Products Regulatory Authority, Earlsfort Terrace, Dublin 2, Tel: +353 1 676 4971, [email protected]. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.

POM S1A

http://www.mhra.gov.uk/yellowcard

mailto:[email protected]

Prescribing Information

Epivir - Lamivudine 300mg tabletsSee Summary of Product Characteristics (SmPC) before prescribing

Indications: HIV in adults, adolescents and children weighing at least 25 kg as part of combination therapy. Dose: Adults: one 300mg tablet daily with or without food. See SmPC for dosage in children and adolescents. Additional formulations available: 150mg tablets and Oral Solution (10mg/mL) – see SmPCs. Elderly: No specific data. Renal impairment: Creatinine clearance <50ml/min: see SmPC for dosage adjustment. Hepatic impairment: no dose adjustment required. Contraindications: Hypersensitivity to any ingredient. Warnings/precautions: High risk of virologicalfailure (when used in a triple nucleoside regimen), immune reactivation syndrome, osteonecrosis, increased weight, lipids, glucose. Monitor LFTs in Hepatitis B/C co-infection. Use with cladribine, emtricitabine or high doses of co-trimoxazole not recommended. When possible, avoid chronic co-administration of sorbitol or other osmotic acting alcohols (see SmPC section 4.5). If unavoidable, consider more frequent viral load monitoring.

Pregnancy/lactation: Not recommended. Avoid breast-feeding. Side effects: See SmPC for full details. Headache, GI disturbance, insomnia, cough, nasal symptoms, rash, alopecia, arthralgia, muscle disorders, fatigue, malaise, fever, blood dyscrasias, pancreatitis, hepatitis, angioedema, rhabdomyolysis, lactic acidosis, peripheral neuropathy. Transient increases in liver enzymes. Basic NHS costs: 30 tablets: £157.51 EU/1/04/298/002. MA holder: ViiV Healthcare UK Ltd, 980 Great West Road, Brentford, Middlesex TW8 9GS. Further information is available from Customer Contact Centre, GlaxoSmithKline UK Ltd, Stockley Park West, Uxbridge, Middlesex UB11 1BT.

Trade marks are owned by or licensed to the ViiV Healthcare group of companies.

Date of approval: June 2018. Zinc code: UK/3TC/0001/18

Adverse events should be reported. For the UK, reporting forms and information can be found at www.mhra.gov.uk/yellowcard or

search for MHRA Yellowcard in the Google Play or Apple App store. Adverse events should also be reported to GSK on 0800 221441.

Adverse events should be reported. For Ireland, adverse events should be reported directly to the HPRA; Freepost, PharmacovigilanceSection, Health Products Regulatory Authority, Earlsfort Terrace, Dublin 2, Tel: +353 1 676 4971, [email protected]. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.

POM S1A

http://www.mhra.gov.uk/yellowcard

mailto:[email protected]

non-inferior efficacy of dolutegravir (dtg) plus ... · •the requirement for lifelong art for hiv...

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