HIV as a chronic disease Implications for public health

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HIV as a chronic diseaseImplications 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

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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

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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
• Male-to-male transmission....1 in 10 to 1 in
  1,600
• Fellatio??.. 0 (CDC) or 6 (SF)
• Parenteral transmission
• Transfusion of infected blood.95 in 100
• 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 3361072-1078,
  1997

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Natural History of HIV infection
Source Fauci, et al, Immu. Mech HIV Inf, 1996
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Acute HIV syndrome oral candidiasis

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AIDS Wasting Syndrome
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AIDS Pneumocystis Jirovecci
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AIDS Kaposis Sarcoma
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Milestones in the response to HIV1981-2010

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

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HIV medicine armamentarium
DLV
NVP
ddC
TDF
ABC
ZDV
d4T
ETV
ddI
EFV
FTC
3TC
87
93
05
04
91
92
94
95
96
97
98
99
00
88
89
90
01
02
03
06
07
08
NRTI
ATV
NFV
LPV/r
SQV
DRV
NNRTI
FPV
APV
TPV
PI
RTV
T-20
MVC
Entry inhibitor
IDV
Integrase inhibitor
RAL
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FDA Approved Antiretroviral Medications

• 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

• 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

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Evolution of HIV Care
1980
2010

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

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

Kathleen Clanon, MD 2007
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HIV Treatment Saves Lives
Mortality and HAART Use Across Time HIV
Outpatient Study, CDC, 1994-2003
Palella et al, JAIDS 2006 4327.
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Impact of ART on TB Incidence
TB among AIDS patients in Brazil
Pulmonary TB
Disseminated TB
www.aids.gov.br/boletim/bol_htm/boletim.htm
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Pill Burden Changes in the landscape
1996 AZT-3TC-Indinavir
20066 TDF-FTC-EFV
MORNING
NIGHT
NOON
NIGHT
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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
• Male-to-male transmission....1 in 10 to 1 in
  1,600
• Fellatio??.. 0 (CDC) or 6 (SF)
• Parenteral transmission
• Transfusion of infected blood.95 in 100
• 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 3361072-1078,
  1997

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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

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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 3632587-259
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Ongoing and Planned Efficacy Trials of PrEP
USA
Thailand
Botswana Kenya Malawi South Africa
Tanzania Uganda Zambia Zimbabwe
Brazil Ecuador Peru
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Impressive scaling up of ART during the last
decade
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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

"
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Universal Access
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Number of people receiving antiretroviral therapy
in low- and middle-income countries, by region,
20022009
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Estimated percentage coverage with antiretroviral
therapy in low- and middle-income countries by
region, based on WHO 2010 and 2006 guidelines,
2008 and 2009
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Retention on antiretroviral therapy up to 48
months, 2008 and 2009
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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
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Before
After
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Challenges

• Long term toxicity, early initiation of ART
• Burden of NCD in HIV
• Ensure retention and adherence and development of
  drug resistance
• Sustainability

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Long-term complications of HAART
Dyslipidaemia/CHD
Abnormalities of Body Fat Distribution
Hepatotoxicity
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Rationale to start ART earlier
PREVENTAIDS CANCERS RENAL CARDIAC LIVER CNS
WAIT
TOXICITY RESISTANCE COST
START
PREVENTTB MTCT New HIV cases
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The Problem of Late Diagnosis

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

500
400
300
CD4 Cell Count (cells/mm3)
200
100
0
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
Calendar Year
Moore RD, et al. CROI 2008. Abstract 805. Graphic
reproduced with permission.
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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

200
180
187
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160
120
100
85
95
55
100
130
100-125
gt 200
87-97
180
Egger M, et al. CROI 2007. Abstract 62.
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HIV patients carry higher burden of NCD
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HCV-Related Cirrhosis Complications expected over
next 10 years
Projected Number of Cases of HCC
andDecompensated Cirrhosis due to HCV
160,000
140,000
120,000
Decompensated cirrhosis
100,000
Cases (n)
80,000
60,000
40,000
Hepatocellular cancer
20,000
0
1950
1960
1970
1980
1990
2000
2010
2020
2030
Year
Davis GL, et al. Gastroenterology 2010.
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Incidence of Fatal Malignancies Among HIV
Patients (N23,437)
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ADM, n112 nADM, n193
18
16
14
12
10
Event Rate/1,000 PYFU
8
6
4
2
0
Age Group
lt30
30-34
35-39
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.
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Retention need of increase both preART and ART
retention
In selected countries, retention on ART at 48
months approaches 75 (UNAIDS)

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

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Poor Adherence Leads to Virologic Failure
N 81 Patients on Protease Inhibitor-Based RX
Paterson Dl et al. Ann Intern Med 200013321-30.
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Poor Adherence leads to Resistance
0
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Factors Associated With Poor Adherence
Psychosocial factors (eg, depression,
homelessness, dementia)
HIV-related stigma
Low literacy level
Current substance abuse
Age-specific factors (eg, visual or cognitive
impairment)
Treatment fatigue
Complicated drug regimens
Difficulty taking meds (eg, problems swallowing
pills, erratic schedule)
Adverse effects of drugs
DHHS. Available at http//aidsinfo.nih.gov/conten
tfiles/AdultandAdolescentGL.pdf.
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Use of generics allowed a huge cost reduction of
PEPFAR programs
Holmes, JAMA 2010
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Total annual resources available for AIDS
(1986-2007)
UNAIDS
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PAHO/WHO

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