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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)
Towards
Universal Access
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
Towards
Universal Access
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
Towards
Universal Access
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