Terapia Antirretroviral en la Infección por el VIH ... · 1. Borges A et al. CROI 2016. Boston,...

Terapia Antirretroviral en la Infección por el VIH (problemas, retos y soluciones)

Dr. Jose R Arribas

@jrarribas

2

Disclosures

Speaker’s Bureau: Gilead Board Member/Advisory Panel: MSD, Gilead, Janssen, ViiV

Terapia Antirretroviral en la infección por el VIH

3

2020 Challenge


Source:

4

HIV testing and care continuum (2016)


Source:

5

ATHENA: Older Patients Becoming More Prevalent in the HIV+ Population

• ATHENA: Observational cohort of 10278 HIV+ pts in the Netherlands

• Modeling study projections:

– Proportion of HIV+ pts ≥ 50 yrs to increase from 28% in 2010 to 73% in 2030

– Median age of HIV+ pts on combination ART to increase from 43.9 yrs in 2010 to 56.6 yrs in 2030

Pro

po

rtio

n o

f H

IV+

Peo

ple


6

Prevalence of COMORBIDITIES. The AGEhIV Cohort Study

Source: Schouten J et al. Clinical Infectious Diseases 2014; 59:1787–1797.

Age-associated non-communicable comorbidity

P<0.0001

Hypertension Non-AIDS cancer

Angina pectoris

Myocardial infarction

Peripheral artery disease

Chronic liver disease

Cardiovascular disease

Par

tici

pan

ts, %

0

20

30

40

50

10

P<0.0001

P=0.010

P=0.017 P=0.015

P=0.043 P=0.034

HIV-negative individuals (n=349)

HIV-infected individuals (n=381)

Subjects ≥45 years with age-associated non-communicable comorbidities, by HIV serostatus (AGEhIV Study, 2010–2012)2


7

ATHENA and Swiss HIV Cohort Studies: Polypharmacy Among HIV+ Pts on ART

Source: Smit M, et al. Lancet Infect Dis. 2015;15:810-818. 2. Hasse B, et al. Clin Inf Dis. 2011:1130-1139


• Predicts that 20% of pts will be taking ≥ 3 meds other than ART in 2030

• 115 (5.2%) of 2233 participants 50-64 yrs of age and 64 (14.2%) of 450 participants ≥ 65 yrs of age received ≥ 4 meds other than ART

< 50 Yrs 50-64 Yrs ≥ 65 Yrs

Swiss HIV Cohort Study (N = 8444)[2]

Prospective Observational study

ATHENA Modeling Study[1]

100

80

60

40

20

0

Par

tici

pan

ts (

%)

n = 5761 n = 2233 n = 450

No comedication 1 comedication 2 comedication 3 comedications 4 or more comedications

16,000

14,000

12,000

10,000

8000

6000

4000

2000

0

Pe

op

le (

n)

3 or more comedications 2 comedications 1 comedication No comedication

2010 2015 2020 2025 2030

8

Remaining challenges: ART optimization

• Worsening of comorbidities – Bone

– Renal

– Cardiovascular

– Liver

– CNS

• Interactions – Polypharmacy

– Recreational drugs


9

Impact of TDF and some PIs on the risk of renal complications


Prospective cohort of 22,603 PLWHIV with a normal baseline renal function* from the D:A:D study at clinics in Europe, the USA and Australia1

ARV exposure and rates of ceGFR≤70 mL/min

from eGFR>90 mL/min, adjusted analysis1

TDF

ATV/r

LPV/r

ceG

FR ≤

70m

L/m

in, a

dju

sted

†

IRR

(95%

CI)

Current ART exposure (months)

Never exposed

4

2

0.5

0.25

1

12–24 <12 24–36 >36

TDF and some PIs are associated with an exacerbated decline of renal function over time1,2

* Defined as eGFR >90 mL/min/1.73m2; † adjusted for baseline eGFR, age, gender, race, HIV risk group, enrolment cohort, CD4 nadir and baseline date, AIDS, HBV/HCV status, smoking status, hypertension, diabetes, CVE, CD4, viral load, and cumulative exposure to ART ART, antiretroviral therapy; ARV, antiretroviral; ATV, atazanavir; CI, confidence interval; CVE, cardiovascular event; ceGFR, Cockroft-Gault estimated glomerular filtration rate; D:A:D, Data collection on Adverse events of Anti-HIV Drugs; eGFR, estimated glomerular filtration rate; HBV, hepatitis B virus; HCV, hepatitis C virus; IRR, incidence rate ratio; LPV, lopinavir; PI, protease inhibitor; PLWHIV, people living with HIV; /r, ritonavir-boosted; TDF, tenofovir disoproxil fumarate 1. Ryom L et al. CROI 2012. Seattle, WA. #865; 2. Nishijima T et al. AIDS 2014;28:1903–1910

10

Risk of fracture for TDF and PIs


CI, confidence interval; PI, protease inhibitor; PYFU, person-years of follow-up; TDF, tenofovir disoproxil fumarate 1. Borges A et al. CROI 2016. Boston, MA. #46; 2. Borges AH et al. Clin Infect Dis 2017;64:1413–1421; 3. Bedimo R et al. AIDS 2012;26:825–831

EuroSIDA participants (n=11,820) across Europe, Israel and Argentina were prospectively followed until last visit or death, to assess fractures and femoral osteonecrosis, from 2004 onwards, resulting in 86,118 PYFU1,2

Crude incidence of new fracture and TDF use1

Cumulative exposure to TDF (years)

14

12

10

8

6

4

2

0

Never Ever Off On 0 1 2 3 4 5 >5

Inci

de

nce

/1,0

00

PY

FU (

95

% C

I)

7.5

10.6

9.1

6.1

8.5 8.1

4.7

7.8

5.6

8.1

4.7

Exposure to TDF

Adapted from Borges A et al. CROI 2016. Boston, MA. #46

Current or past TDF exposure was independently associated with a higher incidence of any fracture, but was not significant for osteoporotic fractures1,2

PIs have also been associated with an increased risk of fracture in some studies3

11

Link between the risk of MI with ABC and some antiretrovirals


* Current or within last 6 months; † approximate test for heterogeneity: p=0.02; ‡ myocardial infarction, stroke, sudden cardiac death, invasive cardiovascular procedures; § primary model; baseline adjustment only for variables on the potential causal pathway between PI/r use and CVD ABC, abacavir; ART, antiretroviral therapy; ATV, atazanavir; CI, confidence interval; CKD, chronic kidney disease; CVD, cardiovascular disease; D:A:D, Data collection on Adverse events of Anti-HIV Drugs; ddI, didanosine; DRV, darunavir; IDV, indinavir; IRR, incidence rate ratio; LPV, lopinavir; MI, myocardial infarction; PI, protease inhibitor; PLWHIV, people living with HIV; PYFU, person-years of follow-up; /r, boosted ritonavir; RR, relative risk; RTV, ritonavir 1. Lundgren JD et al. CROI 2009. Montreal, Canada. #44LB; 2. Ryom L et al. CROI 2017. Seattle, WA. Oral #128LB

Recent exposure to ABC or ddI, and cumulative exposure to IDV, LPV/r or DRV + RTV was associated with increased risk of MI1,2

Relative risk (RR) of MI for different ART1

74,407 53,300 68,469 37,136 #PYFU:

RR of recent* exposure RR of cumulative exposure/year DRV + RTV

NRTI PI†

ddI ABC

Association between CVD IRR and cumulative use of DRV + RTV2§

RR

(9

5%

CI)

IDV LPV/r

2.5

2.0

1.5

1.0

0.5

0.0

Never exposed

Multivariate/ 5 years exp

Univariate/ 5 years exp

CV

D in

cid

en

ce r

ate

rat

io (

95

% C

I) 2.5

2.0

1.5

1.0

0.5

0.0

D:A:D study population of 33,308 PLWHIV, followed up from enrolment until the first MI event, 1st

February 2008, or 6 months after the last clinic visit1

D:A:D study population of 35,711 PLWHIV evaluating the association between CVD‡ and PIs from

2009 to 20162

12

Risk of Suicidality in Pts Treated With EFV-Containing Regimens in ACTG Trials

• Treatment with EFV associated with increased risk of suicidality

– Absolute risk is small

HR: 2.28 (95% CI 1.27-4.10; P = .006)

47 events/5817 PY (8.08/1000 PY)

15 events/4099 PY (3.66/1000 PY)

EFV EFV free

0.05

0.04

0.03

0.02

0.01

0

Pro

bab

ility

192 0 24 48 72 96 120 144 168

Wks to Suicidality

• Trend toward higher incidence of attempted or completed suicide with EFV use (HR: 2.58; 95% CI: 0.94-7.06; P = .065)

• EFV also associated with increased risk of death from substance abuse, homicide, or accident

Multivariable Analysis of Factors Associated With Suicidality in ACTG Clinical Trials

Variable HR (95% CI) P Value

Randomly assigned EFV 2.08 (1.16-3.75) .014

Weight category, kg < 60 vs ≥ 80 60-79 vs ≥ 80

2.69 (1.25-5.79) 1.21 (0.64-2.29)

.022

Hx IDU 2.26 (1.15-4.46) .019

Psychiatric Hx or psychoactive Rx

4.07 (2.32-7.13)

< .001

Source: Mollan K, et al. Ann Intern Med. 2014;161:1-10


13

Better Triple Drug Combinations?

• TAF/FTC/DRV/c vs TDF/FTC-DRV/c naïve: AMBER

• TAF/FTC/DRV/c vs TDF/FTC-bPI suppressed: EMERALD

• TDF/FTC or ABC/3TC- DOR vs TDF/FTC or ABC/3TC- DRV naïve: MK1439-018

• DOR/3TC/TDF vs 2NRTIs-bPI supppressed: MK1439-024

• B/F/TAF naïve: 1489, 1490

• B/F/TAF suppressed: 1844, 1878


14

Better Triple Drug Combinations?





• B/F/TAF naïve: 1489, 1490



15

TAF – A novel prodrug of Tenofovir


TAF results in 90% lower TFV plasma levels

LYMPHOCYTE

TFV

OAT 1 & 3

OAT 1 & 3

RENAL TUBULAR

CELL

TFV

RENAL TUBULAR

CELL

PLASMA

TFV

ESTER

AMIDATE

DIANION

TDF (tenofovir disoproxil fumarate)

TAF (tenofovir

alafenamide)

TFV (tenofovir)

PRO DRUG

LONGER PLASMA HALF-LIFE † - GREATER PLASMA STABILITY

SHORT PLASMA HALF-LIFE†

TFV HIV

GI TRACT

16

TAF vs TDF (FTC/EVG/c) in Naïves: 144 Weeks

Source: Arribas J, et al. 24th CROI; Seattle, WA; February 13-16, 2017. Abst. 453.

At Week 144, E/C/F/TAF was superior to E/C/F/TDF in efficacy difference at both <50 copies/mL; 4.2% (95% CI 0.6%, 7.8%; p=0.02) and <20 copies/mL: 5.4% (95% CI 1.5%, 9.2%; p=0.01)

92 87

84 90

85 80

0

20

40

60

80

100

48 96 144

HIV

-1 R

NA

<5

0 C

op

ies/

mL,

%

Virologic Success

4 5 5 4 4 4

48 96 144

Virologic Failure

4 9 11

6 11

16

48 96 144

No Virologic Data

E/C/F/TAF (n=866)

E/C/F/TDF (n=867)

Wk


17

TAF vs TDF (FTC/EVG/c) in Naïves: Bone and Renal Endpoints

Source: Arribas J, et al. 24th CROI; Seattle, WA; February 13-16, 2017. Abst. 453.

Renal AE D/C, n E/C/F/TAF

n=866

E/C/F/TDF n=867

Total 0 12

Proximal renal tubulopathy 0 4

Increased creatinine/decreased eFGR 0 3

Renal failure 0 2

Nephropathy 0 1

Proteinuria 0 1

Bladder spasm 0 1

-1,3 -1,0 -0,9

-2,8 -2,8 -3,0

-4

-2

0

2

0 48 96 144

Me

an %

Ch

ange

(9

5%

CI)

Week

Spine

∆ 2.0

6 patients discontinued due to decrease in BMD


18

Doravirine (MK-1439)

• Next generation NNRTI

• QD, no food effect

• Low rates of CNS toxicity

• Does not inhibit or significantly induce drug-metabolizing CYP enzymes

• Active against K103N, Y181C, G190A. Selects different mutations than EFV, RPV

• Single tablet doravirine/lamivudine/TDF

• Close to clinic. Phase III ongoing


19

Doravirine. Drive-Ahead Study

Source: Squires K, et al; 9th IAS, Paris, France, July 23-26, 2017; Abst. TUAB0104LB.

23

49

77

87 89 84

20

46

73

81 85

81

0

20

40

60

80

100

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

DOR/3TC/TDF EFV/FTC/TDF

Pe

rce

nta

ge o

f P

arti

cip

ants

(9

5%

CI)

Treatment Week

Difference (95% CI): 3.5 (-2.0, 9.0)

DOR/3TC/TDF is non-inferior to EFV/FTC/TDF at Week 48

Low rate of resistance, with only 1.6% of participants developing resistance to any study drug through Week 48 Significantly less CNS AEs with Doravirine


20

ONCEMRK: RAL 1200 mg QD Noninferior to 400 mg BID at Wk 48 in ART-Naive Pts

Source: Cahn P, et al. AIDS 2016. Abstract FRAB0103LB.

• Multinational, double-blind phase III trial in ART-naive pts with HIV-1 RNA ≥ 1000 c/mL

– Pts randomized to RAL 1200 mg QD vs RAL 400 mg BID + FTC/TDF (N = 802)

• Noninferior Wk 48 HIV-1 RNA < 40 copies/mL in pts with BL HIV-1 RNA > 100,000 copies/mL

– RAL QD: 86.7%; RAL BID: 83.8% (∆ 2.9; 95% CI: -6.5 to 14.1)

• RAL QD associated with overall safety profile similar to RAL BID

100

80

60

40

20

0 Pts

Wit

h H

IV-1

RN

A <

40

co

pie

s/m

L (

%)

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

Treatment Wk

RAL 1200 mg QD +

FTC/TDF

RAL 400 mg BID + FTC/TDF

88.3 88.7 86.5 83.5

78.2

51.9

53.5

76.3

82.1 87.4 87.2

88.9


21

D/C/F/TAF. EMERALD: Study Design

Source: Molina JM, et al; 9th IAS, Paris, France, July 23-26, 2017; Abst. TUAB0101.

Baseline Week 96

Randomisation 2:1

N=1149

Week 48 Primary endpoint

Screening Phase

Treatment Phase

D/C/F/TAF

Extension Phase

≤30 days prior to baseline

Week 24 Interim analysis

D/C/F/TAF

Continue bPI + F/TDF

D/C/F/TAF

Roll-Over Phase

• Previous ART VF allowed

• Absence of history of VF on DRV, and if historical genotype available, absence of DRV RAMs

• Viral load (VL) <50 c/mL for ≥2 months before screening; one VL ≥50 and <200 c/mL within 12 months prior to screening allowed

• Creatinine clearance (by Cockcroft-Gault) ≥50 mL/min


22

EMERALD Study: Efficacy

Source: Molina JM, et al; 9th IAS, Paris, France, July 23-26, 2017; Abst. TUAB0101.

1.8% (n=14)

2.1% (n=8)

0

20

40

60

80

100

DCFTAF(N=763)

Control(N=378)

Pro

po

rtio

n o

f P

atie

nts

(%

)

% Confirmed Virologic Rebound Cumulative

through Week 24

96.3%

0.5% (n=4)

3.1% (n=24)

95.5%

0.8% (n=3)

3.7% (n=14)

0

20

40

60

80

100

Virologicsuccess

Virologicfailure

No virologic data

Pro

po

rtio

n o

f P

atie

nts

(%

)

% Response and Virologic Failure at Week 24 (FDA Snapshot)

VF (50c/mL) at W24 defined as last VL in W24 window ≥50c/mL, or premature discontinuations (≠ AE/death), with last (single) VL ≥50c/mL

(n=735) (n=361)

∆ –0.3% (95% CI: –2.0%, 1.5%)

∆ 0.8% (95% CI: –1.7%, 3.3%)

• Most rebounders (10/14 D/C/F/TAF and 5/8 control) resuppressed (<50c/mL) by Week 24

• No confirmed rebounds ≥200 c/mL

• No discontinuations for VF

• No DRV/primary PI or NRTI RAMs were observed (2 patients genotyped in each group


23

BICTEGRAVIR

• Bictegravir is a novel specific inhibitor of HIV-1 integrase strand transfer activity1

• Structurally related to Dolutegravir. Unboosted

• Active against diverse subtypes of wild-type HIV-1 clinical isolates and HIV-22

• Low cytotoxicity in multiple non-target human cell lines and in primary human hepatocyte2

• Average human T1/2 of ~19 hours, allowing for once daily dosing3

• Close to clinic. Phase III ongoing

Source: 1. Lazerwith S, et al. ASM 2016; Boston, MA. Poster #414 2. Tsiang M, et al. ASM 2016; Boston, MA. Poster #416 3. Gallant J, et al. ASM 2016. Boston, MA. Poster #415


24

GS-1489 STUDY (BICTEGRAVIR): Results

Source: Gallant J, et al; 9th IAS, Paris, France, July 23-26, 2017; Abst. MOAB0105LB.

% Treatment Difference (95% CI)

290 314

293 315

3 314

8 315

14 315

21 314

92,4

1 6,7

93

2,5 4,4

0

20

40

60

80

100

HIV-1 RNA<50 copies/mL

HIV-1 RNA ≥50 copies/mL

No VirologicData

HIV

-1 R

NA

<5

0 c

/mL,

% B/F/TAF (n=314)

DTG/ABC/3TC (n=315)

Virologic Outcome

-12 12 0 -4 -8 4 8

Favors B/F/TAF

Favors DTG/ABC/3TC

- 4.8 3.6

- 0.6

• BF-TAF non-inferior to DTG/ABC/3TC

– No resistance in either study arm

• Lipids not significantly different

• No drug-related renal events

• Significantly less nausea and minor adverse events with BF-TAF


25

Why still Triple?

• DTG-3TC Naïve ACTG 5353, GEMINI

• DTG-3TC Suppressed ASPIRE, TANGO

• DTG-RPV Suppressed SWORD

• CBT-RPV (LA) early switch: FLAIR

• CBT-RPV (LA) stable switch : ATLAS


26

PADDLE: DTG + 3TC (naïve)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


27

Dual therapy with DTG+ 3TC in naïve & suppressed

Source: Cahn P, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. FARB0104LB. Joly I CROI 2017 #458. NCT02582684. NCT02263326. NCT02831673. NCT02831764.

2016

2017

…

DTG + 3TC (ACTG 5353) vs DTG + TDF/FTC (GEMINI9)

2015

DTG + 3TC (Paddle)

DTG + 3TC (LAMIDOL #458) 97% <50 @wk 48

NAÏVE

SUPPRESSED

DTG + 3TC vs 2NRTIs + 3rd drug (ASPIRE) vs TAF-based regimens (TANGO)

DTG + 3TC


28

ISTI + RPV

2016

2017

CAB + RPV vs CAB + ABC/3TC (LATTE-2) 8w: +2.9% 4w: +2.0%

CAB + RPV 4w vs ABC/3TC/DTG

(FLAIR) 2NRTIs + 3rd drug

(ATLAS)

… 2014

2015

CAB + RPV vs 2NRTIs + EFV (LATTE)

-1%

DUAL THERAPY IN SUPPRESSED. SIMPLICITY 2.0 Difference in rates of

supression at 48 weeks (reduced regimen minus triple regimen)

Margolis DA et al. The Lancet Infectious Diseases 2015; 15:1145–1155. Margolis DA et al. AIDS 2016; Durban, South Africa. Abstract THAB0206LB. NCT02938520. NCT02951052

DTG + RPV vs 2NRTIs + 3rd drug

(SWORD, #44LB)

ORAL

LONG ACTING


29

SWORD-1 and SWORD-2 Phase III Study Design

Inclusion criteria

• On stable CAR >6 months before screening

• 1st or 2nd ART with no change in prior regimen due to VF

• Confirmed HIV-1 RNA <50 c/mL during the 12 months before screening

• HBV negative

DTG + RPV (N=513)

Day 1

Screening

Week 148

Identically designed, randomized, multicenter, open-label, parallel-group, non-inferiority studies

CAR (N=511) DTG + RPV

VL <50 c/mL on INI, NNRTI,

or PI + 2 NRTIs

1:1

DTG + RPV

Week 52

Primary endpoint at 48 weeks: subjects with VL <50 c/mL

(ITT-E snapshot)a

Early switch phase Late switch phase Continuation phase

• a-8% non-inferiority margin for pooled data. -10% non-inferiority margin for individual studies

Countries Argentina Australia Belgium Canada France Germany Italy Netherlands Russia Spain Taiwan United Kingdom United States

Source: Llibre et al. CROI 2017; Seattle, WA. Abstract 2421.


30

Snapshot outcomes at week 48 (SWORD-1&2)

Source: Llibre JM CROI 2017 #44LB

0

20

40

60

80

100

Virologicsuccess

Virologicnon-response

No virologicdata

HIV

-1 R

NA

<5

0 c

/mL,

%

Virologic outcomes Adjusted treatment differences (95% CI)a

CAR DTG + RPV

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

-4.3 3.0

Percentage-point difference

DTG + RPV is non-inferior to CAR with respect to snapshot in the ITT-E population (<50 c/mL) at Week 48 in both studies

-3.9 4.2

SWORD-1

SWORD-2

95 96 94 94

<1 <1 <1 2 4 4 5 4

0.2

-0.6

aAdjusted for age and baseline 3rd agent.


31

CAB & RPV LA Nanosuspensions


• CAB is an HIV-1 integrase inhibitor – Oral 30 mg tablet (t½, ~40 hours)

– LA nanosuspension 200 mg/mL (t½, ~20-40 days)

• RPV is an HIV-1 NNRTI – Oral 25 mg tablet (t½, ~50 hours)

– LA nanosuspension 300 mg/mL (t½, ~30-90 days)

Source: Margolis et al. AIDS 2016; Durban, South Africa. Abstract THAB0206LB.

32

LATTE-2 Study: Efficacy


Virologic Outcomes Treatment Differences (95% CI)

Oral IM

10.0%

-12 -9 -6 -3 0 3 6 9 12 15

20.5 -0.6

Q8W IM

[VALOR X].0%

-12 -9 -6 -3 0 3 6 9 12 15

14.4 -8.4

Q4W IM

94

4 2

87

0

13

84

2

14

0

20

40

60

80

100

VirologicSuccess

VirologicNon-Response

No VirologicData

HIV

-1 R

NA

<5

0c/

mL,

%

CAB + RPV LA Q8W (n=115)

CAB + RPV LA Q4W (n=115)

CAB + NRTIs PO (n=56)

Source: Eron J, et al; 9th IAS, Paris, France, July 23-26, 2017; Abst. MOAX0205LB





• B/F/TAF naïve: 1489, 1490


• DTG-3TC Naïve ACTG 5353, GEMINI

• DTG-3TC Suppressed ASPIRE, TANGO

• DTG-RPV Suppressed SWORD

• CBT-RPV (LA) early switch: FLAIR

• CBT-RPV (LA) stable switch : ATLAS

• PRO-140 suppressed

• Vedolizumad suppressed

• VRC01 suppressed

• VRC01-LS + CAB LA suppressed (ACTG 5357)

33

Terapia Antirretroviral en la Infección por el VIH (problemas, retos y soluciones)

Virologic control Forgiveness Residual viremia Persistent inflammation Immunoactivation Penetration in reservorirs Inmmunotherapy


34

Aknowledgments

HIV Unit at La Paz Hospital

Terapia Antirretroviral en la Infección por el VIH ... · 1. Borges A et al. CROI 2016. Boston,...

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