TB & HIV

Both are…….Frequent. Different history

Transmissible/Preventable

Overlapping (>=30%) & Interacting

Treatable infectious diseases Eradication/functional cure Reactivation/relapse/reinfection

Resistance transmitted/selected

200 bc

Nuermberger #127

Add references here

Continued Evolution of HAART

Hatched lines indicate drugs without a naïve licence

24 antiretroviral drugs are approved in the EU: 1987- 20091-4

1. Data available at: http://www.emea.europa.eu/ Accessed Nov 2011. 2. HIVID PI update June 2006: http://www.fda.gov/downloads/Drugs/DrugSafety/DrugShortages/ucm086099.pdf. Accessed Oct 2011 3. Retrovir US PI November 2009: http://us.gsk.com/products/assets/us_retrovir.pdf. Accessed Oct 2011. 4. Videx US PI January 2010: http://packageinserts.bms.com/pi/pi_videx_ec.pdf. Accessed Oct 2011.

1996

2006

1997

1998

1999

2000

2001

2002

2003

2004

2005

1995

2007

2008

2009

1994

1993

1992

1991

1987

AZTEFV

ETR

ddld4T

ddC* 3TCTDF

FTC

ABC

NRTI

EntryInhibitors

Integrase

NNRTI

PIMVC

DRVRTV

SQV

APV

IDV

LPVNFV ATV

TPV

FPV

RAL

NVP

ENF*Discontinued

1. 1981-85: Wait & see2. 1986 : ART, the proof of concept3. 1987-96:ART, suboptimal4. 1997-06: cART. Saving lifes but too toxic5. 2007-11: cART. More convenient & more efective6. 2012- : cART. Realizing about limitations

7. 2012- : cART as a prevention

8. In summary …..

ART: 1981 - 2012

5

50

500

5000

50000

500000

5000000

5 10

15

20

25

30

35

40

45

50

55

60

LTNP (5%)

months

pla

sm

a v

ira

l lo

ad

CTL

nAb

CD4+

1000

200

Control/escape

Exposed/uninfected ?

OI´s, KSLymphomas< 2 years Surv.

asymptomatic symptoms

1. 1981-85: Wait & see2. 1986 : ART, the proof of concept3. 1987-96:ART, suboptimal4. 1997-06: cART. Saving lifes but too toxic5. 2007-11: cART. More convenient & more efective6. 2012- : cART. Realizing about limitations

7. 2012- : cART as a prevention

8. In summary …..

ART: 1981 - 2012

1. 1981-85: Wait & see2. 1986 : ART, the proof of concept3. 1987-96:ART, suboptimal4. 1997-06: cART. Saving lifes but too toxic5. 2007-11: cART. More convenient & more efective6. 2012- : cART. Realizing about limitations

7. 2012- : cART as a prevention

8. In summary …..

ART: 1981 - 2012

Distrtibución porcentual de las pautas de tratamiento en cada año% anual de pautas determ inadas (sobre e l total de pautas adm inistradas en cada año)

0%

20%

40%

60%

80%

100%

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Year

%

1 fármaco 2 fármacos 3nrti 2nrti+1ip 2nrti+1nnrti 2nrti+Rit+1ip Otros 2nrti+Ral

Cooper, Gatell NEJM 1993. ZDV monotherapy. CD4> 400

Month 0 month 3 month 8

Year 1955 ……….

Streptomycin (S) monotherapy or S + Isoniacid (I)

Wild type

I Res.

R Res.

Z Res.

I

I

I+R+P

DELTA STUDY

DELTA 1. OUTCOMEDELTA 1. OUTCOME

ZDV ZDV+ddI ZDV+ddC

TOTAL

(NO. 2131)703 720 708

DEATHS

(%)16.5 9.6 11.6

NEW AIDS

EVENT

OR DEATH

33 20.8 25.9

0.0003

0.03

1. 1981-85: Wait & see2. 1986 : ART, the proof of concept3. 1987-96:ART, suboptimal4. 1997-06: cART. Saving lifes but too toxic5. 2007-11: cART. More convenient & more efective6. 2012- : cART. Realizing about limitations

7. 2012- : cART as a prevention

8. In summary …..

ART: 1981 - 2012

Distrtibución porcentual de las pautas de tratamiento en cada año% anual de pautas determ inadas (sobre e l total de pautas adm inistradas en cada año)

0%

20%

40%

60%

80%

100%

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Year

%

1 fármaco 2 fármacos 3nrti 2nrti+1ip 2nrti+1nnrti 2nrti+Rit+1ip Otros 2nrti+Ral

5

50

500

5000

50000

500000

5000000

5 10

15

20

25

30

35

40

45

50

55

60

months

pla

sm

a v

ira

l lo

ad

HAART1000

400

200

OI´s, KSLymphomas< 2 years Surv.

x

OI’s IN AIDS. CHEMOPROPHYLAXIS THE ERA OF HAARTMORTALITY. HOSPITAL CLINIC. BARCELONA

OI’sOI’s IN AIDS. CHEMOPROPHYLAXIS THE ERA OF HAART IN AIDS. CHEMOPROPHYLAXIS THE ERA OF HAARTMORTALITY. HOSPITAL CLINIC. BARCELONAMORTALITY. HOSPITAL CLINIC. BARCELONA

82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 980

10

20

30

40

50

YEAR

NO. x100 EXPOSED PATIENTS

xYEAR

Lipodystrophy is easy to diagnoseLipodystrophy is easy to diagnose

1. 1981-85: Wait & see2. 1986 : ART, the proof of concept3. 1987-96:ART, suboptimal4. 1997-06: cART. Saving lifes but too toxic5. 2007-11: cART. More convenient & more efective6. 2012- : cART. Realizing about limitations

7. 2012- : cART as a prevention

8. In summary …..

ART: 1981 - 2012

Distrtibución porcentual de las pautas de tratamiento en cada año% anual de pautas determ inadas (sobre e l total de pautas adm inistradas en cada año)

0%

20%

40%

60%

80%

100%

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Year

%

1 fármaco 2 fármacos 3nrti 2nrti+1ip 2nrti+1nnrti 2nrti+Rit+1ip Otros 2nrti+Ral

Primary Endpoint: HIV-1 RNA < 50 copies/mL Study 236-0102

Quad was non-inferior to EFV/FTC/TDF at Week 48

95% CI for Difference

12%

-1. 6 8.8

FavorsEFV/FTC/TDF

3.6

FavorsQuad

0 -12%

88%

7% 5%7% 9%

84%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Virologic

Success

Virologic Non-

Suppression

No W48 Data

Quad EFV/FTC/TDF

Discontinuations due to Adverse EventsStudy 236-0102

Quad(n=348)

EFV/FTC/TDF(n=352)

Discontinuations Due to AE, n (%) 4% 5%

AE leading to discontinuation in >1 subject (%)

Rash and Drug Hypersensitivity 0 1.4%

Renal Abnormalities 1.4% 0

Depression 0.3% 0.9%

Abnormal Dreams 0 0.6%

Fatigue 0.3% 0.3%

Paranoia 0.3% 0.3%

Pacientes activos, nuevos y tratados (anual)

-50

450

950

1450

1950

2450

2950

3450

3950

4450

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Año-Semestres

Nú

mero

de p

acie

nte

s

Current

Treated

New

- Very low mortality- Getting older (> 50% more than 50 years old)- More than 80% undetectable VL

- Young MSM, Inmigrants- 50% < 350 CD4´s

1. 1981-85: Wait & see2. 1986 : ART, the proof of concept3. 1987-96:ART, suboptimal4. 1997-06: cART. Saving lifes but too toxic5. 2007-11: cART. More convenient & more efective6. 2012- : cART. Realizing about limitations

7. 2012- : cART as a prevention

8. In summary …..

ART: 1981 - 2012

Lille, 05/02/07

Life expectancy from age 20-65 of people who started antiretroviral therapy in 2000-8 by CD4 cell count group at start of antiretroviral BMJ 2011;343:d6016 doi: 10.1136/bmj.d6016

Lille, 05/02/07 3232

19%

↵↵↵↵ 80%

20%

33BMS Confidential For internal training purposes only

1586

832

718

827

108

142

146

147

153

160

235

300

302

370

450

510

729

468

47

260

362

376

416

454

100

478

468

713

276

208

0 200 400 600 800 1000 1200 1400 1600 1800

ddI 250 mg c/24h

AZT 300 mg c/12h

d4T 30 mg c/12h

d4T 40 mg c/12h

3TC 300 mg c/24h

FTC 200 mg c/24h

ddI 400 mg c/24h

ABC 300 mg c/12h

TDF 245 mg c/24h

Combivir 1 comp c/12h

Kivexa 1 comp c/24h

Truvada 1 comp c/24h

Trizivir 1 comp c/12h

Atripla 1 comp c/24h

NVP 200 mg c/12h

EFV 600 mg c/24h

ETR 200 mg c/12h

RTV 100 mg c/12h

SQV/r 1500/100 mg c/24h

SQV/r 1000/100 mg c/12h

FPV/r 700/100 mg c/12h

LPV/r 2 comp c/12h

ATV 400 mg c/24h

ATV/r 300/100 mg c/24h

DRV/r 800/100 mg c/24h

DRV/r 600/100 mg c/12h

TPV/r 500/200 c/12h

RAL 400 mg c/12h

MVC 1 comp c/12h

T-20 90 mg c/12h

EU

RO

S P

ER

PA

CIE

NT

-YE

AR

Dru

gs

Dir

ect

Co

sts

CO

ST

/EF

FIC

AC

Y 7000

7500

8000

8500

9000

9500

10000

10500

11000

11500

12000

12500

13000

13500

14000

14500

15000

15500

16000

TDF/FTC/EFA

TDF/FTC+DRV/r

TDF/FTC+ATV/r

TDF/FTC+RAL

TDF/FTC+NVP

TDF/FTC+LPV/r

ABC/3TC+LPV/r

ABC/3TC+EFA

Blasco, Gatell et al. EIMC 2011

Hospital manager

Prime minister

Pharmacy

Yesterday: Science

Today & Tomorrow: Science+money+generics

And, above all, access to every person who needs it and in every country was and still is an unresolved issue

Starting Antiretrovirals in 2012

1. 1981-85: Wait & see2. 1986 : ART, the proof of concept3. 1987-96:ART, suboptimal4. 1997-06: cART. Saving lifes but too toxic5. 2007-11: cART. More convenient & more efective6. 2012- : cART. Realizing about limitations

7. 2012- : cART as a prevention

8. In summary …..

ART: 1981 - 2012

clinicaloptions.com/hiv

HIV/AIDS Highlights From Rome

HPTN 052: HIV Transmission Reduced by 96% in Serodiscordant Couples

Single transmission in patient in immediate ART arm believed to have occurred close to time therapy began and prior to HIV-1 RNA suppression

Total HIV-1 Transmission Events: 39(4 in immediate arm and

35 in delayed arm; P < .0001)

Linked Transmissions: 28

Unlinked or TBD Transmissions: 11

P < .001

Immediate Arm: 1

Delayed Arm: 27

Cohen MS, et al. IAS 2011. Abstract MOAX0102. Cohen MS, et al. N Engl J Med. 2011;[Epub ahead of print].

clinicaloptions.com/hiv

HIV/AIDS Highlights From Rome

Efficacy of HIV Prevention Strategies From Randomized Clinical Trials

Abdool Karim SS, et al. Lancet. 2011;[Epub ahead of print].

1000 20 40 60 80

Efficacy (%)

Study Effect Size, % (95% CI)

ART for prevention; HPTN 052, Africa, Asia, Americas

PrEP for discordant couples;Partners PrEP, Uganda, Kenya

PrEP for heterosexual men and women; TDF2, Botswana

Medical male circumcision; Orange Farm, Rakai, Kisumu

PrEP for MSMs; iPrEX, Americas, Thailand, South Africa

Sexually transmitted diseases treatment; Mwanza, Tanzania

Microbicide;CAPRISA 004, South Africa

HIV vaccine;RV144, Thailand

96 (73-99)

73 (49-85)

63 (21-84)

54 (38-66)

44 (15-63)

42 (21-58)

39 (6-60)

31 (1-51)

1. 1981-85: Wait & see2. 1986 : ART, the proof of concept3. 1987-96:ART, suboptimal4. 1997-06: cART. Saving lifes but too toxic5. 2007-11: cART. More convenient & more efective6. 2012- : cART. Realizing about limitations

7. 2012- : cART as a prevention

8. In summary …..

ART: 1981 - 2012

Codirecció

Dr. Bonaventura ClotetDr. Josep Maria Gatell

Coordinador Científic

Christian Brander (Universitat de Harvard)

Recerca d’una vacuna

8 línies de recerca,més de 60 investigadors

Infectious Diseases & AIDS Units. Hospital Clinic. Barcelona. Spain