HIV as a chronic disease

Implications for public health

Massimo N Ghidinelli MD HIV/AIDS STI Pan American Health Organization
World Health Organization

J2J Global Health Media Training

Washington 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

Adults and children estimated to be living with HIV 2009

Eastern Europe Western & Central Europe & Central Asia North America [1.2 million 2.0 million] Caribbean

1.5 million

[720 000 910 [1.3 million 1.6 million] 000] East Asia Middle East & North Africa [560 000 1.0 million] South & South-East Asia [3.7 million 4.6 million] Oceania [50 000 64 000]

820 000

1.4 million

770 000

[400 000 530 000] [220 000 270 000] Central & South America [1.2 million 1.6 million] Sub-Saharan Africa [20.9 million 24.2 million]

240 000

460 000

4.1 million

22.5 million

1.4 million

57 000

Total: 33.3 million [31.4 million 35.3 million]

Estimated number of adults and children newly infected with HIV 2009
Eastern Europe Western & Central Europe & Central Asia North America [44 000 130 000] Caribbean

70 000

[110 000 160 [23 000 40 000] 000] East Asia 82 000 [48 000 140 000] Middle East & North Africa [61 000 92 000] Sub-Saharan Africa [1.6 million 2.0 million]

31 000

130 000

[13 000 21 000] Central & South America

17 000

75 000

South & South-East Asia [240 000 320 000] Oceania [3400 6000]

270 000

1.8 million

[70 000 120 000]

92 000

4500

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)

Routes of Exposure and HIV INFECTION ROUTE RISK OF INFECTION Sexual Transmission a. Female-to-male transmission..1 in 700 to 1 in 3,000 b. Male-to-female transmission....1 in 200 to 1 in 2,000 c. Male-to-male transmission....1 in 10 to 1 in 1,600 d. Fellatio??.. 0 (CDC) or 6% (SF) Parenteral transmission a. Transfusion of infected blood.95 in 100 b. Needle sharing.1 in 150 c. Needle stick..1 in 200 d. Needle stick /AZT PEP1 in 10,000 Transmission from mother to infant a. Without AZT treatment....1 in 4 b. With AZT treatment.Less than 1 in 10 Royce, Sena, Cates and Cohen, NEJM 336:1072-1078, 1997
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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: Kaposis Sarcoma

Milestones in the response to HIV 1981-2010

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

HIV medicine armamentarium

DLV ddC ZDV ddI NVP d4T 3TC ABC EFV TDF FTC ETV

87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 0304 05 0607 08 NRTI NNRTI PI

Entry inhibitor Integrase inhibitor

SQV

NFV RTV IDV

LPV/r APV

ATV FPV TPV T-20 MVC RAL DRV

FDA Approved Antiretroviral Medications

NRTI Abacavir ABC Didanosine Emtricitabine Lamivudine Stavudine D4T Zidovudine Tenofovir TDF NNRTI Efavirenz EFV NevirapineNVP Etravirine

DDI FTC 3TC AZT

Protease Inhibitor Atazanavir Darunavir Fosamprenavir Indinavir Lopinavir/rtv Nelfinavir Ritonavir Saquinavir Tipranavir Fusion Inhibitor Enfuvirtide CCR 5 antagonist Maraviroc

ATV DRV FPV IDV LPV/rtv NFV RTV SQV TPV T-20 MVC

ETR

Integrase inhibitor RAL Raltegravir

Evolution of HIV Care

1980 2010

Disease Care Acute Reactive Focus on dx/rx Customized care Spiritual MD role central

Health Care Chronic Proactive Focus on behavior Standardized care Practical Pt role central

Kathleen Clanon, MD 2007

16

HIV Treatment Saves Lives

Mortality and HAART Use Across Time
14 12 10 8 6 4 2 0
4 5 19 9 19 9 19 9

Slide 17

HIV Outpatient Study, CDC, 1994-2003 0.9

0.8 0.7 0.6 0.5 0.4 0.3 Patients on HAART 0.2 0.1 0 Deaths per 100 PY

6 19 97 19 98 19 99 20 00 20 01 20 02 20 03

Year

Palella et al, JAIDS 2006; 43:27.

Patients on HAART

Deaths per 100 PY

Slide 18

Impact of ART on TB Incidence

Annual incidence in AIDS cases
0.15

TB among AIDS patients in Brazil

0.10

Pulmonary TB Disseminated TB

0.05

0.00 1985

1990 Mono

Dual

1995

Triple 2000 therapy

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

Pill Burden: Changes in the landscape

1996: AZT-3TC-Indinavir
MORNING NOON NIGHT

20066: TDF-FTC-EFV
NIGHT

ART 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

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Routes of Exposure and HIV

INFECTION ROUTE RISK OF INFECTION Sexual Transmission a. Female-to-male transmission..1 in 700 to 1 in 3,000 b. Male-to-female transmission....1 in 200 to 1 in 2,000 c. Male-to-male transmission....1 in 10 to 1 in 1,600 d. Fellatio??.. 0 (CDC) or 6% (SF) Parenteral transmission a. Transfusion of infected blood.95 in 100 b. Needle sharing.1 in 150 c. Needle stick..1 in 200 d. Needle stick /AZT PEP1 in 10,000 Transmission from mother to infant a. Without AZT treatment....1 in 4 b. 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

Ongoing and Planned Efficacy Trials of PrEP

USA Thailand

Brazil Ecuad or Peru

Botswan a Kenya Malawi South Africa Tanzani a Uganda

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 Communiqu: 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, 20022009

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

Abnormalities of Body Fat Distribution

Hepatotoxicity

Rationale to start ART earlier

PREVENT AIDS CANCERS RENAL CARDIAC LIVER CNS

WAIT TOXICITY RESISTANCE COST

START PREVENT TB MTCT New HIV cases

Earlier Initiation
clinicaloptions.com/hiv

The Problem of Late Diagnosis

CD4+ cell counts typically low among treatment-naive patients first presenting for HIV care
500

CD4+ Cell Count (cells/mm3)

400 300 200 100 0

96 97 98 99 00 01 02 03 04 05 06 19 19 19 19 20 20 20 20 20 20 20 Calendar Year

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

Earlier Initiation
clinicaloptions.com/hiv

When Is Antiretroviral Therapy Started?

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

187 100

200 120

180 85 100

160 55

19 130 95 > 200

100-125 180 87-97

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

HIV patients carry higher burden of NCD

HCV-Related Cirrhosis Complications expected over next 10 years

Projected Number of Cases of HCC and Decompensated Cirrhosis due to HCV
160,000 140,000 120,000 Decompensated cirrhosis

Cases (n)

100,000 80,000 60,000 40,000 20,000 0 1950 1960 1970

Hepatocellular cancer 1980 1990 Year 2000 2010 2020 2030

Davis GL, et al. Gastroenterology 2010.

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

20 18 16
Event Rate/1,000 PYFU

ADM, n=112 nADM, n=193

14 12 10 8 6 4 2 0 <30 30-34 35-39 Age Group 40-44 45-49 50-54 55-59 60-64 65-69
ADM, AIDS-defining malignancies; nADM, non-AIDS defining malignancies; PFYU, person-years of follow-up

Monforte A. 14th CROI, 2007. Abstract 84.

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

100 80 HIV RNA >400 copies/ml

N = 81 Patients on Protease Inhibitor-Based RX

82%

60 40 20

67% 55%

71%

22%
0 > 94% 90-94% 80-89% 70-79% < 70% Level of Adherence

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

Poor Adherence leads to Resistance

1 0,8

Resistance

0,6 0,4 0,2 0 0 10 20 30 40 50 60 70 75 80 85 90 95 100

Adherence

Factors Associated With Poor Adherence

Psychosocial factors (eg, depression, homelessness, dementia) Current substance abuse Treatment fatigue Complicated drug regimens Adverse effects of drugs HIV-related stigma Low literacy level

Age-specific factors (eg, visual or cognitive impairment) Difficulty taking meds (eg, problems swallowing pills, erratic schedule)

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

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