hiv as a chronic disease (dr. massimo ghidinelli)

HIV as a chronic diseaseImplications for public health

Massimo N Ghidinelli MDHIV/AIDS STI

Pan American Health OrganizationWorld Health Organization

J2J Global Health Media TrainingWashington D.C., 11 June 2011

OUTLINE• Overview of HIV epidemic, morbidity,

mortality and modes of transmission

• Natural history of HIV infection, progression to AIDS

• Anti Retroviral Therapy (ART), applications and impact on HIV/AIDS

• Response to HIV: global steps and achievements in treatment and care

• Challenges and future directions

Total: 33.3 million [31.4 million – 35.3 million]

Western & Central Europe

820 000[720 000 – 910 000]

Middle East & North Africa460 000

[400 000 – 530 000]

Sub-Saharan Africa22.5 million

[20.9 million – 24.2 million]

Eastern Europe & Central Asia1.4 million

[1.3 million – 1.6 million]

South & South-East Asia4.1 million

[3.7 million – 4.6 million]

Oceania57 000

[50 000 – 64 000]

North America1.5 million

[1.2 million – 2.0 million]

Central & South America

1.4 million[1.2 million – 1.6 million]

East Asia770 000

[560 000 – 1.0 million]Caribbean240 000

[220 000 – 270 000]

Adults and children estimated to be living with HIV 2009

Estimated number of adults and children newly infected with HIV 2009

Western & Central Europe

31 00031 000[23 000 – 40 000]

Middle East & North Africa75 00075 000

[61 000 – 92 000]

Sub-Saharan Africa1.8 million1.8 million

[1.6 million – 2.0 million]

Eastern Europe & Central Asia

130 000 130 000 [110 000 – 160 000]

South & South-East Asia270 000270 000

[240 000 – 320 000]

Oceania45004500

[3400 – 6000]

North America70 000

[44 000 – 130 000]

Central &South America

92 00092 000[70 000 – 120 000]

East Asia82 00082 000

[48 000 – 140 000]

Caribbean17 000

[13 000 – 21 000]

Total: 2.6 million [2.3 million – 2.8 million]

Over 7000 new HIV infections a day in 2009

About 97% are in low and middle income countries

About 1000 are in children under 15 years of age

About 6000 are in adults aged 15 years and older, of whom:

─ almost 51% are among women

─ about 41% are among young people (15-24)

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Routes of Exposure and HIV INFECTION ROUTE RISK OF INFECTIONSexual Transmissiona. Female-to-male transmission………..1 in 700 to 1 in 3,000b. Male-to-female transmission……...….1 in 200 to 1 in 2,000c. Male-to-male transmission………...….1 in 10 to 1 in 1,600d. Fellatio??…………………………….. 0 (CDC) or 6% (SF)

Parenteral transmissiona. Transfusion of infected blood………….95 in 100b. Needle sharing………………………….1 in 150c. Needle stick…………………………..…1 in 200d. Needle stick /AZT PEP…………………1 in 10,000

Transmission from mother to infanta. Without AZT treatment………...…….1 in 4b. With AZT treatment………………….Less than 1 in 10

Royce, Sena, Cates and Cohen, NEJM 336:1072-1078, 1997

Natural History of HIV infection

Source: Fauci, et al, Immu. Mech HIV Inf, 1996

Acute HIV syndrome : oral candidiasis

AIDS: Wasting Syndrome

AIDS: Pneumocystis Jirovecci

AIDS: Kaposi’s Sarcoma

Milestones in the response to HIV1981-2010

• HIV discovery• Diagnostics• Viral load• Epidemiology• Pathogenesis• Prevention • Effective therapy• Potential eradication• Development of a vaccine

’87 ’91 ’92 ’94 ’95 ’96 ’97 ’98 ’99 ’00’88 ’89 ’90 ’01 ’02 ’03’93 ’05’04 ’06

ddC

3TC

NNRTI

NRTI

PI

Entry inhibitor

ddI

IDV

SQV LPV/r

TDFNVP

DRV

TPV

T-20

ZDV d4TABC

DLV

EFV FTC

RTV

NFV ATV

FPV

’07

MVC

HIV medicine armamentarium

APV

ETV

’08

Integrase inhibitorRAL

FDA Approved Antiretroviral Medications

NRTI• Abacavir ABC• Didanosine DDI• Emtricitabine FTC• Lamivudine 3TC• Stavudine D4T• Zidovudine AZT• Tenofovir TDF

NNRTI• Efavirenz EFV• Nevirapine NVP• Etravirine ETR

Integrase inhibitor• Raltegravir RAL

Protease Inhibitor• Atazanavir ATV• Darunavir DRV• Fosamprenavir FPV• Indinavir IDV• Lopinavir/rtv LPV/

rtv• Nelfinavir NFV• Ritonavir RTV• Saquinavir SQV• Tipranavir TPV

Fusion Inhibitor• Enfuvirtide T-20

CCR 5 antagonist• Maraviroc MVC

16

Evolution of HIV Care

Disease Care AcuteReactiveFocus on dx/rxCustomized careSpiritualMD role central

Health CareChronic Proactive

Focus on behaviorStandardized care

PracticalPt role central

Kathleen Clanon, MD 2007

1980 2010

Slide 17

HIV Treatment Saves Lives

02468

101214

Year

Death

s p

er

100 P

Y

00.10.20.30.40.50.60.70.80.9

Patients

on H

AA

RT

Patients on HAART

Deaths per 100 PY

Palella et al, JAIDS 2006; 43:27.

Mortality and HAART Use Across Time

HIV Outpatient Study, CDC, 1994-2003

Slide 18

0.00

0.05

0.10

0.15

1985 1990 1995 2000

An

nu

al

inci

den

ce i

n A

IDS

ca

ses

Pulmonary TB

Disseminated TB

Mono Dual Triple therapy

TB among AIDS patients in Brazil

www.aids.gov.br/boletim/bol_htm/boletim.htm

Impact of ART on TB Incidence

Pill Burden: Changes in the landscape

MORNING NIGHTNOON

1996: AZT-3TC-Indinavir 20066: TDF-FTC-EFVNIGHT

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ART ApplicationsART Applications• Treatment of HIV disease (HAART)

• Prevention of Mother-to-Child-Transmission (PMTCT)

• Post-exposure Prophylaxis (PEP)

• Pre-exposure Prophylaxis (PrEP, iPrEP)

• Prevention ART-population based ART

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Promising results for the prevention of mother-to-child transmission of HIV since 1994

Courtesy: James Mc Intyre

Routes of Exposure and HIV INFECTION ROUTE RISK OF INFECTIONSexual Transmissiona. Female-to-male transmission………..1 in 700 to 1 in 3,000b. Male-to-female transmission……...….1 in 200 to 1 in 2,000c. Male-to-male transmission………...….1 in 10 to 1 in 1,600d. Fellatio??…………………………….. 0 (CDC) or 6% (SF)

Parenteral transmissiona. Transfusion of infected blood………….95 in 100b. Needle sharing………………………….1 in 150c. Needle stick…………………………..…1 in 200d. Needle stick /AZT PEP…………………1 in 10,000

Transmission from mother to infanta. Without AZT treatment………...…….1 in 4b. With AZT treatment………………….Less than 1 in 10

Royce, Sena, Cates and Cohen, NEJM 336:1072-1078, 1997

Pre-Exposure Prophylaxis• Daily anti-HIV medication taken by HIV-

negatives – Started prior to potential exposure – Continued throughout periods of risk– Added to existing prevention efforts

• Concept proven effective in other situations:– Malaria– Prevention of mother-to-child transmission of HIV

• Would be an addition to, not a replacement for, existing prevention strategies

iPrEx: Efficacy of oral TDF-FTC PrEP in HIV negative MSM

Use of TDF-FTC was associated with a 44% risk of HIV acquisition (MITT analysis) In adherent individuals protection was close to 90%

Grant, N Engl J Med 2010; 363:2587-259

Thailand

BotswanaKenyaMalawiSouth Africa TanzaniaUgandaZambiaZimbabwe

BrazilEcuadorPeru

USA

Ongoing and Planned Efficacy Trials of PrEP

Impressive scaling up of ART during the last decade

Launching PEPFAR“AIDS can be prevented. Anti-retroviral drugs can extend life for many years. And the cost of those drugs has dropped from $12,000 a year to under $300 a year -- which places a tremendous possibility within our grasp. Ladies and gentlemen, seldom has history offered a greater opportunity to do so much for so many”

January 28, 2003

"

Universal Access

2005 G8 Summit at Gleneagles, Final Communiqué:“…working with WHO, UNAIDS and other international bodies to develop and implement a package of HIV prevention, treatment and care, with the aim of as close as possible to universal access to treatment for all those who need it by 2010.”

Number of people receiving antiretroviral therapy in low- and middle-income countries, by region, 2002–2009

Estimated percentage coverage with antiretroviral therapy in low- and middle-income countries by region, based on WHO 2010 and 2006 guidelines, 2008 and 2009

Retention on antiretroviral therapy up to 48 months, 2008 and 2009

Percentage of pregnant women living with HIV receiving antiretrovirals for preventing mother-to-child transmission of HIV in low- and middle-income countries by region, 2005, 2008 and 2009

Before After

Challenges

• Long term toxicity, early initiation of ART

• Burden of NCD in HIV

• Ensure retention and adherence and development of drug resistance

• Sustainability

Long-term complications of HAART

Dyslipidaemia/CHD

Hepatotoxicity

Abnormalities ofBody Fat Distribution

Rationale to start ART earlier Rationale to start ART earlier

START

WAIT

PREVENTAIDSCANCERSRENALCARDIAC LIVER CNS

TOXICITYRESISTANCECOST PREVENT

TB MTCTNew HIV cases

clinicaloptions.com/hivEarlier Initiation

The Problem of Late Diagnosis

CD4+ cell counts typically low among treatment-naive patients first presenting for HIV care

Moore RD, et al. CROI 2008. Abstract 805. Graphic reproduced with permission.

0

100

200

300

400

500

CD

4+ C

ell

Co

un

t (c

ells

/mm

3 )

1996

Calendar Year1997

19981999

20002001

20022003

20042005

2006

clinicaloptions.com/hivEarlier Initiation

187

100

180

20019

87-97 > 200

160

130

180

100-125

12085

100 55 95

Egger M, et al. CROI 2007. Abstract 62.

Review of data from 2003-2005 from 176 sites in 42 countries (N = 33,008)

Since 2000, CD4+ cell count at initiation in developed countries stable at approximately 150-200 cells/mm3, increasing in sub-Saharan Africa from 50-100 cells/mm3

When Is Antiretroviral Therapy Started?

HIV patients carry higher burden of NCD

HCV-Related Cirrhosis Complications expected over next

10 years

Davis GL, et al. Gastroenterology 2010.

Projected Number of Cases of HCC andDecompensated Cirrhosis due to HCV

1950 1960 1970 1980 1990 2000 2010 2020 2030

Year

Cas

es (

n)

160,000

0

140,000

120,000

100,000

80,000

60,000

40,000

20,000

Decompensated cirrhosis

Hepatocellular cancer

Incidence of Fatal Malignancies Among HIV Patients (N=23,437)

Monforte A. 14th CROI, 2007. Abstract 84. ADM, AIDS-defining malignancies; nADM, non-AIDS defining malignancies; PFYU, person-years of follow-up

Eve

nt R

ate/

1,00

0 P

YF

U

Age Group<30 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69

0

2

20

18

16

14

12

10

8

6

4

ADM, n=112nADM, n=193

Retention: need of increase both preART and ART retention

Approximately only 1/3 of elegible patients initiate ARV timely. Kranzer et al (2010)

In selected countries, retention on ART at 48 months approaches 75% (UNAIDS)

Poor Adherence Leads to Virologic Failure

22%

55%

67% 71%

82%

0

20

40

60

80

100

HIV

RN

A >

400

cop

ies/

ml

> 94% 90-94% 80-89% 70-79% < 70%

Level of Adherence

Paterson Dl et al. Ann Intern Med 2000;133:21-30.

N = 81 Patients on Protease Inhibitor-Based RX

Poor Adherence leads to Resistance

0

0,2

0,4

0,6

0,8

1

0 10 20 30 40 50 60 70 75 80 85 90 95 100

Adherence

Res

ista

nce

Factors Associated With Poor Adherence

Low literacy level

Age-specific factors (eg, visual or

cognitive impairment)

Psychosocial factors (eg, depression,

homelessness, dementia)

Current substance abuse

HIV-related stigma

Complicated drug regimens Difficulty taking meds (eg, problems swallowing

pills, erratic schedule)Adverse effects of drugs

Treatment fatigue

DHHS. Available at: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.

Use of generics allowed a huge cost reduction of PEPFAR

programs

Holmes, JAMA 2010

Total annual resources available for AIDS (1986-2007)

UNAIDS

525 23rd St. NWWashington, D.C. 200037

(202) 974-3000

www.paho.org/hiv

PAHO/WHO