Inibidores da Integrase do HIV em População com Idade mais ...regist2.virology-education.com/2017/HIVClinicalFora/Brazilian/08... · Número de Anos Perdidos e Risco de Morte Atribuído

Marcia Rachid

bull Membro do Comitecirc Assessor para Terapia Antirretroviral do Departamento Nacional de ISTAIDSHepatites Virais do Ministeacuterio da Sauacutede

bull Coordenadora da Cacircmara Teacutecnica de AIDS do CREMERJbull Poacutes-graduada em Imunologia Cliacutenica ndash Instituto de Poacutes-Graduaccedilatildeo Meacutedica Carlos Chagasbull Mestre em Doenccedilas Infecciosas e Parasitaacuterias ndash UFRJ

marciarachidgmailcom

Inibidores da Integrase do HIV em Populaccedilatildeo com Idade mais Avanccedilada

Polifarmaacutecia e Comorbidades

Conflito de Interesses

bull Sem conflito de interesses a declarar

Aspectos que devem ser considerados

bull O estigma e a discriminaccedilatildeo em relaccedilatildeo ao HIV permanecem altamente

prevalentes em qualquer faixa etaacuteria

bull Fatores geneacuteticos hormonais nutricionais e o estilo de vida podem interferir

negativamente e podem piorar com o passar do tempo

bull Problemas de sauacutede mental satildeo comuns e podem progredir com a idade

bull Comorbidades e polifarmaacutecia satildeo questotildees crescentes na populaccedilatildeo com

mais de 50 anos e podem comprometer adesatildeo

bull As interaccedilotildees medicamentosas satildeo frequentes e uma preocupaccedilatildeo

significativa com maior risco de toxicidade

bull Os esquemas terapecircuticos baseados em inibidores da integrase satildeo eficazes

bem tolerados tecircm menos interaccedilotildees medicamentosas menor toxicidade e

alta barreira agrave resistecircncia

Risco de adoecimento por Tuberculose eacute de doze a vinte

vezes maior do que na populaccedilatildeo geral

Karim Lancet 2009

Coinfecccedilatildeo

HIV-Tuberculose


HIV-Hepatite CClausen LN et al World J Gastroenterol 2014 2012132ndash12143

Alteraccedilotildees Metaboacutelicas Endoacutecrinas e Lipodistrofia

bull Alteraccedilotildees metaboacutelicas (dislipidemia hiperglicemia diabetes) costumam ser associadas agrave esteatose hepaacutetica e ao maior risco de eventos cardiovasculares

bull Podem ocorrer pancreatite ou hiperamilasemia acidemia ou acidose laacutetica

bull Se houver depoacutesitos de gordura satildeo centrais abdome tronco mamas giba regiatildeo cervicofacial (lipohipertrofia) Se houver lipoatrofia eacute perifeacuterica (face e membros)

bull Podem ocorrer hipotireoidismo e hipogonadismo (alteraccedilotildeeshormonais costumam ser mais comuns nos homens com reduccedilatildeo de niacuteveis de testosterona)

Disfunccedilatildeo mitocondrial

bull lipodistrofia

bull neuropatias

bull esteatose

hepaacutetica

bull miopatia

bull pancreatite

bull acidose laacutetica

bull intoleracircncia agrave

glicose

resistecircncia agrave

insulina diabetes

TG e de LDL

reduccedilatildeo HDL

ARV (ITRN)

ITRcitocinas

HIV

bull Gama-DNA polimerasebull transportebull estresse oxidativobull apoptosebull fosforilaccedilatildeobull proteoacutelisebull glicosilaccedilatildeo

Alteraccedilotildees associadas aos Inibidores da Protease


insulina

GLUT4

GLUT1

reduccedilatildeo do armazenamento

de gordura nos adipoacutecitos

Interferecircncia na

utilizaccedilatildeo da glicose

nos muacutesculos e

adipoacutecitos

aumento de lipiacutedeos no

fiacutegado maior produccedilatildeo e

secreccedilatildeo de VLDL

hiperlipidemia

lipodystrophy

Interferecircncia na adipogecircnese

Siacutentese de TG

apoB VLDL

HIV e IPlipodistrofia

Alteraccedilotildees Metaboacutelicas Endoacutecrinas e Risco Cardiovascular

Infecccedilatildeo pelo HIV e Risco Cardiovascular

- 60 das pessoas com HIV tecircm placas nas arteacuterias cardiacuteacas mesmo semsinaissintomas

- Haacute relaccedilatildeo direta com a inflamaccedilatildeo decorrente da infecccedilatildeo pelo HIV

HIV e Aterosclerose

HIV-1-Associated Atherosclerosis Unraveling the Missing LinkJ Am Coll Cardiol 2017 Jun 2769(25)3084-3098 doi 01016jjacc201705012Kearns A Gordon J Burdo TH Qin X

Doenccedila cardiovascular incluindo aterosclerose e outras complicaccedilotildees associadas eacute causa

crescente de morbidade e mortalidade nos pacientes infectados pelo HIV na era poacutes-

HAART

Terapia antirretroviral comorbidades associadas tais como dislipidemia abuso de drogas

infecccedilotildees oportunistas e outros fatores de risco relacionados a haacutebitos de vida satildeo

importantes tanto para precipitar como para piorar a aterosclerose

Tipo 1 resulta espontaneamente da instabilidade da placa ateroscleroacutetica

Tipo 2 ocorre por desequiliacutebrio entre consumooferta de oxigecircnio vasoespasmo (por exemplo infecccedilatildeo ou uso de cocaiacutena)

EVENTOS CARDIOVASCULARES

Infarto Agudo do Miocaacuterdio

FatoresAnos Perdidos de Vida Idade 35 a 80 anos (95 CI)

Risco de morte

HIV + que nunca fumaram

(HIV + nunca que fumaram vs controlesque nunca fumaram)

51 (44ndash58) 03

Controles fumantes

(controles fumantes vs controles quenunca fumaram)

36 (31ndash40) 344

HIV + fumantes

(HIV + fumantes vs HIV + que nuncafumaram)

123 (115ndash130) 615

Tabagismo Mortalidade e HIV Helleberg Clin Infect Dis 2013

Nuacutemero de Anos Perdidos e Risco de Morte Atribuiacutedo agrave Populaccedilatildeo de Fumantes e com HIV

Em um local onde o tratamento da infecccedilatildeo pelo HIV eacute organizado e gratuito pessoas portadoras do HIV e

fumantes perdem mais anos de vida para o tabagismo do que para o proacuteprio viacuterus Satildeo 123 anos de vida

perdidos para o cigarro O excesso de mortalidade de fumantes eacute triplicado e o risco de morte associado

ao tabagismo eacute duplicado entre HIV + em comparaccedilatildeo agrave populaccedilatildeo natildeo fumante mesmo com HIV

NA-ACCORD Fumo hipertensatildeo arterial e niacuteveis de colesterol aumentam

risco de IAM em portadores do HIV

bull Metanaacutelise retrospectivabull Eventos validados de 7 coortes cliacutenicas

NA-ACCORD 12000 -122013 bull N = 29515[1]

ndash Fraccedilatildeo atribuiacutevel agrave populaccedilatildeo proporccedilatildeo de IM evitaacuteveis pela prevenccedilatildeo de fatores de risco modificaacuteveis relacionados com o HIV e tradicionais

ndash 347 pacientes (12) apresentavam IM de tipo 1 devido agrave ruptura da placa

ndash A anaacutelise de sensibilidade foi feita para 16687 pacientes (57) com dados de IMC 227 apresentaram IM tipo 1

ndash ~ 40 de reduccedilatildeo IM possiacutevel atraveacutes da prevenccedilatildeo do tabagismo TC elevado ou hipertensatildeo independentemente do IMC

1 Althoff KN et al CROI 2017 Abstract 130 2 Shepherd L et al CROI

2017 Abstract 131 Slide credit

clinicaloptionscom

bull Em outra anaacutelise separada (DAD) a interrupccedilatildeo do fumo reduziu as taxas globaisde cacircncer apoacutes 1 ano (exceto pulmatildeo quepermaneceu alta mesmo apoacutes 5 anos)[2]

Ajuste para idade sexo raccedila e fatores de risco

listados daggerP lt 05

Adjusted Population Attributable Fractions for MI[1]

MI

BMI Subgrou

p

Traditional MI risk factors

Smoking 38dagger 36

Elevated TC 43dagger 39dagger

HTN 41dagger 39dagger

All 3 (smoking TC HTN) 86

HIV-related MI risk factors

DM 2 4

CKD 3 3

CD4+ cell count 10dagger 14dagger

VL 6 8

AIDS 2 -1

HCV coinfection 8dagger 14dagger

bull Uso recente de ABC associado com ~70 aumento risco de IM

ndash Uso recente definido como ainda em uso ou interrupccedilatildeo dentrodos uacuteltimos seis meses

bull Exposiccedilatildeo cumulativa

ndash ao ABC foi associada com pequeno aumento do risco de IM

ndash ao Lopinavirr foi associada com aumento do risco de IM

Estudo DAD

Risco Cardiovascular

Abacavir e Risco de Infarto Agudo do Miocaacuterdio e Doenccedila Cerebrovascularna era HAART

R Bedimo12 A Westfall3 H Drechsler12 P Tebas41VA North Texas Healthcare System Medicine Dallas United States 2University of Texas Southwestern MedicalCenter Medicine Dallas United States 3University of Alabama at Birmingham Medicine Birmingham United

States 4University of Pennsylvania Medicine Philadelphia United States

19424 pacientes acompanhados por cerca de 4 anos (75311 pessoas-ano) 278 IAM e 868 AVC entre pessoas com mais fatores de risco para DCV incluindo hepatite C e doenccedila renal

Taxa global IAM 369 por 1000 pessoas-ano AVC 1168 por 1000 pessoas-ano

Abacavir associado a maior risco de IAM (hazard ratio [HR] 127 ou 27 aumento do risco) e de AVC (HR 117)

Anaacutelise foi repetida apoacutes controle dos fatores de risco conhecidos paraDCV e condiccedilotildees coexistentes (idade hiperlipidemia hipertensatildeo diabetes tabagismo) e a associaccedilatildeo entre abacavir e IAM ou AVC deixou de ser forte e deixou de ser estatisticamente significante

Pacientes HIV+ com problemas renais satildeo mais medicados com abacavir comoalternativa ao tenofovir e jaacute tecircm maior risco de DCV e de AVC o que passoua ser considerado fator de confusatildeo na anaacutelise

DAD exposiccedilatildeo ao ATVRTV ou DRVRTV e risco

cardiovascular

bull Prospectivo Jan2009 (BL) ateacute o primeiro evento CV uacuteltima visita + 6 meses ou 01022016

bull (N = 35711)

ndash 1157 pts (32) apresentaram DCV (IM AVE morte suacutebita) ou se submeteram a um procedimento cardiacuteaco invasivo

bull Exposiccedilatildeo cumulativa a DRVRTV estaacute associada a risco CV - anaacutelisemultivariada 59 risco aumentadocom 5 anos de uso

ndash Associaccedilatildeo natildeo parece ser mediada pordislipidemia

bull Limitaccedilotildees Fatores de confusatildeo potencialmente natildeomensuraacuteveis num estudo observacional ndash Natildeo foipossiacutevel diferenciar entre DRVRTV 800100 QD vs DRVRTV 600100 BID

bull Natildeo avaliou uso de estatinas natildeo ajustou para supressatildeo viral Fumo atual apenas Exposiccedilatildeo aotabaco em maccedilosano natildeo foi avaliada exposiccedilatildeopreacutevia a IP de primeira geraccedilatildeo natildeo avaliada

Ryom L et al CROI 2017 Abstract 128LB

Incidence Rates of CVD andCumulative Exposure to ATV+RTV and DRV+RTV

ATV+RTV DRV+RTV

Cumulative years of drug exposure

200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)

Incidecircncia de Doenccedilas Crocircnicas

Aumenta Exponencialmente com a Idade

Idade

INC

IDEcirc

NC

IA

Idade eacute o maior fator de riscoSlide cortesia de Peter Reiss

Schouten J et al Clin Infect Dis 2014

Comorbidades relacionadas agrave idade

A IDADE Eacute FATOR DE RISCO INDEPENDENTE E NAtildeO MODIFICAacuteVEL PARA DCV

J GUNTER ET AL ACTA CLINICA BELGICA INTERNATIONAL JOURNAL OF CLINICAL AND LABORATORY MEDICINE

Prevalecircncia de Fatores Predisponentes

para Fragilidade

KKooij et al 8th Netherlands Conference on HIV Pathogenesis Epidemiology Prevention and Treatment Amsterdam November 2014

Causas de Morte 1999-2011

Continuous Increase of Cardiovascular Diseases Diabetes and Non-HIV Related Cancers

as Causes of Death in HIV-Infected Individuals in Brazil An Analysis of Nationwide Data

Paula AA Schechter M Tuboi SH Faulhaber JC Luz PM et al (2014) PLOS ONE 9(4)

e94636 httpsdoiorg101371journalpone0094636

bull 12366853 atestados

bull 151706 (123) HIVAIDS

ATVr DRVr EFV RPV DTG RAL ABC FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan

Interaccedilotildees com Antihipertensivos

No clinically

significant

interaction

expected

Potential interaction may

require

dose adjustment or

monitoring

Potential interaction

no dose adjustment

required

ATVr DRVr EFV RPV DTG RAL

AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin

Interaccedilotildees Medicamentosas com Hipolipemiantes e Hipoglicemiantes

No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required

Interaccedilotildees com Medicamentos que atuam no SNC

BOOSTED FREE AGENTS BOOSTED AGENTS

DTGII RAL EFV ETV RPV EVGc DRVr

Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam

GHB (gamma hydroxybutyrate)

heroin (diamorphone)

hydrocodone

hydromorphone

ketamine

pethidine (meperideine)

methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis

lysergic acid dietheylamide (LSD)

phencyclidine (PCP angle dust)

Further information (in vivo in vitro or from label) at wwwhiv-druginteractionsorg

These drugs should not be co-administered

Potential interaction-may require close monitoring alteration of drug dosage or timing of administration

No clinically significant expected

Dose do DTG interfere nos niacuteveis de Metformina

Haacute aumento da exposiccedilatildeo plasmaacutetica da metformina

quando coadministrada com DTG e o efeito produzido

(PK) no niacutevel de metformina eacute dose-dependente do DTG

01

10

100

0 4 8 12

Metformin AlonePeriod 1Metformin + DTG 50 mgq24h

Metf

orm

in c

on

cen

trati

on

(microg

mL

)

Nominal time (hours)

Metformin alone Period

1

Metformin + DTG 50 mg

q24h


3

01

10

100

0 4 8 12

Metformin AlonePeriod 1Metformin + DTG 50mg q12h



1


q12h


3

bull Anaacutelise retrospectiva de adultos HIV+ que mudaram o esquema para

outros contendo DTG e fazendo uso concomitante de metformina

(n=15)

bull DTG natildeo alterou a resposta ao uso da metformina nos pacientes

diabeacuteticos

ndash Natildeo houve diferenccedila significante nos niacuteveis de glicose em jejum nem

na concentraccedilatildeo de HbA1 observados antes e depois da troca para

DTG

Na vida real natildeo houve diferenccedila significativa na glicemia de jejum nem na Hb glicada antes e depois da troca para DTG

Raltegravir treatment outcomes among older patients and those with comorbidities A sub-analysis of the CRICKET study

BHIVA 2016 April Manchester UKCB Jones1 J Tan1 J Robinson1 H Tate1 H Lamba1

1Merck Sharp ampDohme Limited Hertford Road Hoddesdon Hertfordshire

- Comorbidades satildeo frequentes

- 70 das pessoas fazem uso de outros medicamentos

- Supressatildeo viral alcanccedilada em cerca de 85 dos casos

independentemente da idade das comorbidades e do uso

de outros medicamentos


n=19215 RAL em 83 dos esquemas (n=1428)

Switching From a Boosted Protease Inhibitor (PIr) Based Regimen to a

Dolutegravir (DTG) Regimen in Virologically Suppressed Patients With

High Cardiovascular Risk (Framingham Score gt10 or Age gt 50 Years) Is

Non-Inferior and Decreases Lipids The NEAT 022 Study

JM Gatell1 L Assoumou2 G Moyle3 L Waters4 E Martinez5 H-J

Stellbrink6 G Guaraldi7 S de Wit8 F Raffi9 A Pozniak10 on behalf of

NEAT022 Study Group

1Hospital ClinicIDIBAPS University of Barcelona Infectious Diseases Barcelona Spain 2Sorbone Universites INSERM

UPMC Univ Paris 06 IPLESP UMRS 1136 Paris France 3Chelsea and Westminster Hospital London United Kingdom4Mortimer Market Center London United Kingdom 5Hospital ClinicIDIBAPS University of Barcelona Barcelona Spain6Infectiologisches Centrum Hamburg Germany 7University of Modena and Reggio Emilia Modena Italy 8Saint Pierre

University Hospital Universiteacute Libre de Bruxelles Brussels Belgium 9CHU

Hotel-Dieu Nantes Nantes France 10Chelsea amp Westminster Hospital London United Kingdom

bull Multicecircntrico (32 siacutetios) 96 semanas (Europeu seis paiacuteses)

prospectivo randomizado aberto (open-label) ensaio de natildeo-

inferioridade (~10)

bull Criteacuterio de elegibilidade

ndash HIV-1 RNA lt 50 cpml por ge 6 meses em terapia tripla com 2 ITRN + IPr

ndash Idade gt50 anos eou score de risco de Framingham gt10 em 10 anos

ndash Sem mutaccedilotildees de resistecircncia documentadas e sem falha viral preacutevia

confirmada durante uso de terapia antirretroviral

Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)

Immediate switching Deferred switching

Primary endpoint

Adapted from

reference 62

Resultado Impacto nos lipiacutedeos

No changes in the utilization of lipid lowering agents

Around 30 in each arm and both at baseline and week 48

bull Mais de 48 semanas pacientes virologicamente suprimidos alto risco

cardiovascular idade acima de 50 anos score de Framingham gt10

terapia tripla (2 anaacutelogos e IPr)

ndash Troca para DTG natildeo foi inferior

ndash Houve melhora do colesterol total e das fraccedilotildees em todos os

subgrupos

ndash Poucas falhas viroloacutegicas e nenhuma mutaccedilatildeo de resistecircncia

selecionada

bull Toleracircncia boa e similar em ambos os braccedilos

bull Subestudos em andamento para avaliar marcadores bioloacutegicos (ECG

e outros)

bull Trocar por DTG mostrou benefiacutecio potencial e reduziu o risco

cardiovascular

Conclusotildees

Gatell et al IAS 2017 Paris France Slides TUAB0102

ElvitegravirCobicistatEmtricitabineTenofovirDF Demonstrates Comparable Efficacy

and FavorableTolerability to EfavirenzEmtricitabineTenofovir DF and to Ritonavir-

boosted Atazanavir Plus EmtricitabineTenofovir

DF in Patients ge50 Years at Week 96

Studies 102 and 103 ndash Age Sub-analysis

J Gallant1 D Hardy2 F Bredeek3 K Workowski4 W Towner5 L Dau6 H Liu6 J Curley6 M Rhee6 D Piontkowsky6 J

Szwarcberg6

1Southwest CARE Center Santa Fe NM 2David Geffen School of Medicine-UCLA Los Angeles CA

3Metropolis Med Group San Francisco CA 4Emory Univ Atlanta GA 5Kaiser Permanente Los Angeles CA 6Gilead

Sciences Foster City CA

- Taxas de supressatildeo similares aos pacientes com lt 50 anos

- Baixa taxa de resistecircncia (n=1)

- Menor taxa de tonteira e alteraccedilotildees do sono em relaccedilatildeo a ATVr

- Menor alteraccedilatildeo da funccedilatildeo renal em comparaccedilatildeo ao ATVr

Caracteriacutesticas dos Antirretrovirais

In the presence of confirmed or suspected integrase resistance DTG should be taken twice daily preferably

with food

Once dailyNo food

requirementsNo time-of-day requirements Booster-free Notes

DTG Yes Yes Yes YesCan be taken with orwithout food

EVGc Yes No Yes NoTake with food (recommended)

RAL No Yes Yes Yes Twice-daily dosing

EFV Yes No No YesBedtime dosing on empty stomach (recommended)

RPV Yes No Yes Yes Take with food (mandatory)

ATVbooster Yes No Yes NoTake with food (recommended)

DRVbooster Yes No Yes NoTake with food (recommended)

Yes

No

Efeitos adversos relacionados ao SNC em pessoas virgens de terapia

SPRING-2 FLAMINGO SINGLE ARIA

Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)

Drug-relateddagger 6 (14) 3 (07) 4 (17) 5 (21) 43 (104) 28 (67) 5 (20) 1 (04)

Led to withdrawaldagger 0 0 0 0 1 (02) 4 (10) 1 (04) 0

Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)

Drug-relateddagger 1 (02) 2 (05) 1 (04) 0 4 (10) 11 (26) 0 1 (04)

Led to withdrawaldagger 0 0 0 0 0 4 (10) 0 0

Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)

Drug-relateddagger 1 (02) 2 (05) 0 0 13 (31) 19 (45) 1(04) 1 (04)

Led to withdrawaldagger 0 0 0 0 1 (02) 6 (14) 0 0

Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)

Drug-relateddagger 0 0 1 (04) 0 0 4 (10) 1 (04) 0

Led to withdrawaldagger 0 2 (05) 1 (04) 0 0 1 (02) 0 0

All third agents were part of a three-drug regimen containing two NRTIs

Higher rates in SINGLE trial could potentially be attributed to proactive CNS questionnaire use and double-blind comparison with

EFV daggerProportion of population

Coorte OPERA Incidecircncia de alteraccedilotildees no SNC

Prospectively-captured routine clinical data (electronic medical records) from 79 outpatient clinics

across 15 states in the United States daggerAll agents listed were given with other ARVs Daggeranxiety

depression insomnia or suicidality

ARV antiretroviral RPV rilpivirine

39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50

Subjects with history of

CNS disordersDagger

CNS disordersDagger

(all subjects)

lsquoNewrsquo CNS disordersDagger

occurring in subjects

with no prior history

of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG

bull OPERA database analysis 11539 subjects in routine US practice who received regimensdagger containing

DTG (19) EFV (14) RAL (8) DRV (15) RPV (15) or EVG (29)

DTG prescriptions include

a high proportion of

subjects with CNS

disorders at baseline

Frequency of lsquonewrsquo

CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study

DTG n=2180 EFV n=1622 RAL n=917 DRV n=1759 RPV n=1758 EVG n=3303

Eficaacutecia Superior do Dolutegravir

In SINGLE 414 patients received DTG + ABC3TCdaggerDTG 50 mg + ABC 600 mg3TC 300 mg were used Bioequivalence has been

demonstrated26

DaggerIn FLAMINGO on Day 1 in the DTG arm 163 and 79 patients received TDFFTC

or ABC3TC respectively in the DRVr arm 162 and 80 patients received

TDFFTC or ABC3TC respectivelysectIn SPRING-2 on Day 1 in the DTG arm 242 and 169 patients received TDFFTC

or ABC3TC respectively in the RAL arm 247 and 164 patients received TDFFTC

or ABC3TC respectively In SAILING DTG and raltegravir were combined with a background regimenparaIn STRIIVING 551 virologically suppressed patients were randomised

274 received TRIUMEQ (DTGABC3TC) and 277 continued their current ART

regimens (42 PIs 27 INIs and 31 NNRTIs)In VIKING-3 patients received DTG + current failing regimen on Days 1ndash7 From

Day 8 on patients received DTG in combination with an optimised background

regimen

ART = antiretroviral therapy BID = twice daily

BR = background regimen cART = combination antiretroviral therapy DRVr =

darunavirritonavir DTG = dolutegravir FTC = emtricitabine

OBR = optimised background regimen PI = protease inhibitor

QD = once daily RAL = raltegravir TDF = tenofovir disoproxil fumarate

AltamenteexperimentadosExperimentadosVirgens de terapia

Superior

efficacy

Non-inferior

Non-

comparative

Superior efficacy vs DRVr

at Weeks 48 and 96

FLAMINGO

DTG 50 mg + 2 NRTIs QD vs DRVr 800

mg100 mg + 2 NRTIs QD (N=484)

Superior efficacy vs EFVTDFFTC

at Weeks 48 96 and 144

SINGLE

DTG + ABC3TCdagger QD vs EFVTDFFTC

QD (N=833)

Comparable efficacy vs RAL

at Weeks 48 and 96

SPRING-2

DTG 50 mg QD + 2 NRTIs vs RAL 400

mg BID + 2 NRTIs (N=822)

Superior efficacy vs RAL

up to Week 48

SAILING

DTG 50 mg QD + BR vs RAL 400 mg BID

+ BR (N=715)

Maintained efficacy following treatment

switch vs continuation of current ARV

regimen

up to Week 24

STRIIVING

DTGABC3TC QD vs cART (N=551)

Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)

Superior efficacy vs ATVr

at Week 48 in women

ARIA

DTGABC3TC vs ATVr

300 mg100 mg + TDFFTC QD (N=495)

Comparando a ITRNN IPr e INI

Farmacovigilacircncia DTG ndash Brasil

Janeiro a Junho 2017

bull Total de 39990 pacientes em uso de DTG

bull 22683 iniciaram com DTG

bull 17307 trocaram de RAL para DTG

bull Ateacute 30 Junho 2017 3086 questionaacuterios preenchidos

para avaliar efeitos adversos

Nenhum 93 (n=2879)

Algum 7 (n=207)

Adele Benzaken Ministry of Health of Brazil Enhanced ARV Monitoring in

Countries Brazil IAS 2017

Fatos e Desafios

- A expectativa de vida das pessoas vivendo com HIV (PVHIV) vem aumentando e eacute similar a da populaccedilatildeo em geral especialmente em paiacuteses desenvolvidos- Quanto maior o tempo de evoluccedilatildeo maior o risco de comorbidades infecciosas e natildeo infecciosas incluindo doenccedilas metaboacutelicas endoacutecrinas e cardiovasculares - Fatores de risco aleacutem do proacuteprio HIV precisam ser controlados dieta tabagismo sedentarismo alcoolismo dislipidemia alteraccedilotildees da glicose hipertensatildeo arterial e outros- Interaccedilotildees medicamentosas satildeo comuns pelo acuacutemulo de novos medicamentos para diferentes comorbidades

Smit M Brinkman K Geerlings S et al Future challenges for clinical care of an ageing population infected with HIV a modelling study Lancet Infect Dis 201515(7)810ndash818Dyslipidemia Atherosclerosis and Cardiovascular DiseaseAn Increasingly Important Triad in an Aging Population Living With HIVJane A OHalloran Claudette S Satchell Patrick WG MallonFuture Virology 20138(10)1021-1034

Conflito de Interesses

bull Sem conflito de interesses a declarar
















Karim Lancet 2009


HIV-Tuberculose









bull lipodistrofia

bull neuropatias

bull esteatose

hepaacutetica

bull miopatia

bull pancreatite



glicose


insulina diabetes

TG e de LDL


ARV (ITRN)

ITRcitocinas

HIV




insulina

GLUT4

GLUT1





nos muacutesculos e

adipoacutecitos




hiperlipidemia

lipodystrophy


Siacutentese de TG

apoB VLDL






HIV e Aterosclerose




HAART









Risco de morte



51 (44ndash58) 03

Controles fumantes


36 (31ndash40) 344

HIV + fumantes


123 (115ndash130) 615










NA-ACCORD 12000 -122013 bull N = 29515[1]







clinicaloptionscom





MI

BMI Subgrou

p


Smoking 38dagger 36





DM 2 4

CKD 3 3


VL 6 8

AIDS 2 -1







Estudo DAD











cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios


















Karim Lancet 2009


HIV-Tuberculose









bull lipodistrofia

bull neuropatias

bull esteatose

hepaacutetica

bull miopatia

bull pancreatite



glicose


insulina diabetes

TG e de LDL


ARV (ITRN)

ITRcitocinas

HIV




insulina

GLUT4

GLUT1





nos muacutesculos e

adipoacutecitos




hiperlipidemia

lipodystrophy


Siacutentese de TG

apoB VLDL






HIV e Aterosclerose




HAART









Risco de morte



51 (44ndash58) 03

Controles fumantes


36 (31ndash40) 344

HIV + fumantes


123 (115ndash130) 615










NA-ACCORD 12000 -122013 bull N = 29515[1]







clinicaloptionscom





MI

BMI Subgrou

p


Smoking 38dagger 36





DM 2 4

CKD 3 3


VL 6 8

AIDS 2 -1







Estudo DAD











cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios





Karim Lancet 2009


HIV-Tuberculose









bull lipodistrofia

bull neuropatias

bull esteatose

hepaacutetica

bull miopatia

bull pancreatite



glicose


insulina diabetes

TG e de LDL


ARV (ITRN)

ITRcitocinas

HIV




insulina

GLUT4

GLUT1





nos muacutesculos e

adipoacutecitos




hiperlipidemia

lipodystrophy


Siacutentese de TG

apoB VLDL






HIV e Aterosclerose




HAART









Risco de morte



51 (44ndash58) 03

Controles fumantes


36 (31ndash40) 344

HIV + fumantes


123 (115ndash130) 615










NA-ACCORD 12000 -122013 bull N = 29515[1]







clinicaloptionscom





MI

BMI Subgrou

p


Smoking 38dagger 36





DM 2 4

CKD 3 3


VL 6 8

AIDS 2 -1







Estudo DAD











cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios









bull lipodistrofia

bull neuropatias

bull esteatose

hepaacutetica

bull miopatia

bull pancreatite



glicose


insulina diabetes

TG e de LDL


ARV (ITRN)

ITRcitocinas

HIV




insulina

GLUT4

GLUT1





nos muacutesculos e

adipoacutecitos




hiperlipidemia

lipodystrophy


Siacutentese de TG

apoB VLDL






HIV e Aterosclerose




HAART









Risco de morte



51 (44ndash58) 03

Controles fumantes


36 (31ndash40) 344

HIV + fumantes


123 (115ndash130) 615










NA-ACCORD 12000 -122013 bull N = 29515[1]







clinicaloptionscom





MI

BMI Subgrou

p


Smoking 38dagger 36





DM 2 4

CKD 3 3


VL 6 8

AIDS 2 -1







Estudo DAD











cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios




bull lipodistrofia

bull neuropatias

bull esteatose

hepaacutetica

bull miopatia

bull pancreatite



glicose


insulina diabetes

TG e de LDL


ARV (ITRN)

ITRcitocinas

HIV




insulina

GLUT4

GLUT1





nos muacutesculos e

adipoacutecitos




hiperlipidemia

lipodystrophy


Siacutentese de TG

apoB VLDL






HIV e Aterosclerose




HAART









Risco de morte



51 (44ndash58) 03

Controles fumantes


36 (31ndash40) 344

HIV + fumantes


123 (115ndash130) 615










NA-ACCORD 12000 -122013 bull N = 29515[1]







clinicaloptionscom





MI

BMI Subgrou

p


Smoking 38dagger 36





DM 2 4

CKD 3 3


VL 6 8

AIDS 2 -1







Estudo DAD











cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios





insulina

GLUT4

GLUT1





nos muacutesculos e

adipoacutecitos




hiperlipidemia

lipodystrophy


Siacutentese de TG

apoB VLDL






HIV e Aterosclerose




HAART









Risco de morte



51 (44ndash58) 03

Controles fumantes


36 (31ndash40) 344

HIV + fumantes


123 (115ndash130) 615










NA-ACCORD 12000 -122013 bull N = 29515[1]







clinicaloptionscom





MI

BMI Subgrou

p


Smoking 38dagger 36





DM 2 4

CKD 3 3


VL 6 8

AIDS 2 -1







Estudo DAD











cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios







HIV e Aterosclerose




HAART









Risco de morte



51 (44ndash58) 03

Controles fumantes


36 (31ndash40) 344

HIV + fumantes


123 (115ndash130) 615










NA-ACCORD 12000 -122013 bull N = 29515[1]







clinicaloptionscom





MI

BMI Subgrou

p


Smoking 38dagger 36





DM 2 4

CKD 3 3


VL 6 8

AIDS 2 -1







Estudo DAD











cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios






HIV e Aterosclerose




HAART









Risco de morte



51 (44ndash58) 03

Controles fumantes


36 (31ndash40) 344

HIV + fumantes


123 (115ndash130) 615










NA-ACCORD 12000 -122013 bull N = 29515[1]







clinicaloptionscom





MI

BMI Subgrou

p


Smoking 38dagger 36





DM 2 4

CKD 3 3


VL 6 8

AIDS 2 -1







Estudo DAD











cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios



HIV e Aterosclerose




HAART









Risco de morte



51 (44ndash58) 03

Controles fumantes


36 (31ndash40) 344

HIV + fumantes


123 (115ndash130) 615










NA-ACCORD 12000 -122013 bull N = 29515[1]







clinicaloptionscom





MI

BMI Subgrou

p


Smoking 38dagger 36





DM 2 4

CKD 3 3


VL 6 8

AIDS 2 -1







Estudo DAD











cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios








Risco de morte



51 (44ndash58) 03

Controles fumantes


36 (31ndash40) 344

HIV + fumantes


123 (115ndash130) 615










NA-ACCORD 12000 -122013 bull N = 29515[1]







clinicaloptionscom





MI

BMI Subgrou

p


Smoking 38dagger 36





DM 2 4

CKD 3 3


VL 6 8

AIDS 2 -1







Estudo DAD











cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios




Risco de morte



51 (44ndash58) 03

Controles fumantes


36 (31ndash40) 344

HIV + fumantes


123 (115ndash130) 615










NA-ACCORD 12000 -122013 bull N = 29515[1]







clinicaloptionscom





MI

BMI Subgrou

p


Smoking 38dagger 36





DM 2 4

CKD 3 3


VL 6 8

AIDS 2 -1







Estudo DAD











cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios






NA-ACCORD 12000 -122013 bull N = 29515[1]







clinicaloptionscom





MI

BMI Subgrou

p


Smoking 38dagger 36





DM 2 4

CKD 3 3


VL 6 8

AIDS 2 -1







Estudo DAD











cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios








Estudo DAD











cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios












cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios




cardiovascular


bull (N = 35711)








ATV+RTV DRV+RTV


200

150

100

50

40

30

20

0

Incid

en

ce r

ate

1000 P

YF

U (

95

CI)



Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios





Idade

INC

IDEcirc

NC

IA







para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios








para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios






para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios




para Fragilidade










EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios











EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios




EVGc

FTCTA

F

EVGc

FTCTD

F

Antihypert

ensiv

eagents

Amlodipine

Atenolol

Bisoprolol

Enalapril

Felodipine

Indapamide

Lisinopril

Losartan

Nifedipine

Olmesartan

Perindopril

Valsartan


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring


no dose adjustment

required


AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios




AB

C FTC 3TC TDF

EVGc

FTCTA

F

EVGc

FTCTD

F

Lip

id-l

ow

ering a

gents

Atorvastatin

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Antidia

betic a

gents

Glibenclamid

e (Glyburide)

Linagliptin

Metformin

Nateglinide

Saxagliptin

Sitagliptin


No clinically

significant

interaction

expected


require

dose adjustment or

monitoring

Do not co-

administer


no dose adjustment

required




Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios






Stim

ula

nts

amyl nitrate

cocaine

ecstasy (MDMA)

mephedrone

methamphetamine

Dep

ress

ants

alcohol

alprazolam

codeine

diazepam



hydrocodone

hydromorphone

ketamine


methadone

midazolam (oral)

morphine

oxycodone

temazepam

triazolam

Hal

luci

no

gen

s

cannabis











01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios







01

10

100

0 4 8 12


Metf

orm

in c

on

cen

trati

on

(microg

mL

)



1


q24h


3

01

10

100

0 4 8 12




1


q12h


3



(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios





(n=15)


diabeacuteticos



DTG


















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios



















NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios











NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios









NEAT022 Study Group







inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios





inferioridade (~10)






Desenho do Estudo

Randomization

11

stratified by

country

PIr + 2NRTs (PIr)

DTG + 2NRTIs (DTG)

Week 0 48

96

DTG + 2NRTIs (DTG)


Primary endpoint

Adapted from

reference 62









subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios











subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios








subgrupos


selecionada



e outros)


cardiovascular

Conclusotildees








Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios









Szwarcberg6










with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios





with food

Once dailyNo food









Yes

No



Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios





Cases n ()

DTG

N=411

RAL

(n=411)

DTG

(n=242)

DRVr

(n=242)

DTG

(n=414)

EFV

(n=419)

DTG

(n=248)

ATVr

(n=247)

Insomnia

Overall 25 (6) 20 (5) 20 (8) 16 (7) 71 (17) 52 (12) 10 (4) 8 (3)



Anxiety

Overall 17 (4) 23 (6) 13 (5) 9 (4) 28 (7) 30 (7) 5 (2) 8 (3)



Depression

Overall 29 (7) 21 (5) 16 (7) 12 (5) 35 (8) 44 (11) 9 (4) 11sect (4)



Suicidality

Overall 4 (lt1) 6 (1) 4 (2) 1 (lt1) 3 (lt1) 7 (2) 3 (1) 4 (2)











39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios








39 40

3134

28

24

0

10

20

30

40

50

18

2119 18

1718

0

10

20

30

40

50

1314 14

12 1314

0

10

20

30

40

50


CNS disordersDagger

CNS disordersDagger

(all subjects)




of that disorder

CNS disordersDagger

during treatment

more common with

RAL than DTG





subjects with CNS



CNS AEs similar

across regimens

Su

bje

cts

(

)

Baseline On-study




demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios





demonstrated26









regimen







Superior

efficacy

Non-inferior

Non-

comparative


at Weeks 48 and 96

FLAMINGO





SINGLE


QD (N=833)


at Weeks 48 and 96

SPRING-2




up to Week 48

SAILING


+ BR (N=715)



regimen

up to Week 24

STRIIVING


Sustained efficacy

up to Week 48

VIKING-3

DTG 50 mg BID + OBR

(N=183)


at Week 48 in women

ARIA

DTGABC3TC vs ATVr










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios










Nenhum 93 (n=2879)

Algum 7 (n=207)



Fatos e Desafios



Fatos e Desafios



Documents

Inibidores da Integrase do HIV em População com Idade mais ...regist2.virology-education.com/2017/HIVClinicalFora/Brazilian/08... · Número de Anos Perdidos e Risco de Morte Atribuído