Download HIV/AIDS DOES IT MATTER TO A UTAH PEDIATRICIAN ?

32 years
KRISTEN RIES, MD
MAY 7, 2013
PUBLIC HEALTH
1
OBJECTIVES & OUTLINE
• The objective of this talk is to describe the
aging HIV epidemic
• The emphasis will be on the epidemic in
the First World
– Overview of history of the epidemic as it ages
– Review the aging epidemiology
– Review how age affects the disease process
HIV/AIDS 2013
It is a humbling experience to see how far we have come
with the hard sciences and the reality of human nature.
The epidemic is global, but today we will mostly
concentrate on 1st world.
What happens in one community affects all
communities.*
KMR
*World economy
HIV/AIDS FACTS
• First described 1981
• Cause – HIV-1
• Group M - West C Africa
– Clades (subtypes) - A-K
• Group N - Cameroon
• Group O - West C Africa
--HIV 2
2009 WOROBEY M et.al. CROI Paper 2009
Molecular epidemiology/ archival HIV-1
Pandemic likely 100 years old
Changes in human ecology allowed it
Thomson et al JID 196:1120, 2007
AIDS FACTS-ORIGIN
– Zoonosis
• HIV - 1
– Group M - Chimpanzee - SIVcpzPtt
– Group N - Chimpanzee - SIVcpzPtt
– Group O - ? Gorilla
SIVgor
• HIV - 2- Sooty mangabee
1st documented + serum
1959- Kinshasa DRC
HIV/AIDS US HISTORY
• 1981* AIDS = GRID, fear, stigma, discrimination-- A
Social Disease
• 1983 HIV Virus isolated - fear, refusal to treat,
discrimination --- ASO’s, proliferation of the ARTS ( film,
books, paintings etc”)
• 1985 Tests for HIV antibodies- fear, discrimination
caregivers - passion for what they did = “Hero’s”
• 1987 AZT first drug available
• 1988 PCR (Viral Load ) tests available
• 1996 HAART (Highly Active Antiretroviral
Therapy) available - Vancouver conference
Stigma
Discrimination
Fear
 providers
Neuro\cognitive
HIV/AIDS 1981 - 1996
HIV/AIDS
Socioeconomic Issues
Insurance
OI’s
&
Kaposi’s
sarcoma
KMR
ACA
Psychological Stress
Stigma
Low self esteem
Rejection
Disclosure
Prevention
Rx is
prevention!
10
Hepatitis C
&
20
interventions
Substance Abuse
Hepatitis
Hepatitis
BB
CURE
Neuro\cognitive
VACCIN
E
HIV/AIDS
HIV/AIDS
Diabetes
Hypertension
Hyperlipidemia
Hypogonadism
Neuropathy
Cancers
Strokes
Heart Attacks
OI’s
OI’s
Tumors
Tumors
Women
Pregnancy
Aging
K Ries 2013Version
Major Mental
illness
Socioeconomic Issues
Poor
Homeless
Unemployed
Uninsured
Underinsured
Incarcerated
HIV/AIDS US HISTORY
• 2000-2012- adequate care for chronic
disease is possible
– Caregiver burnout/ loss of caregivers
– Less providers entering the field
– Public apathy
– Affected apathy
– No $
- Talking about Cure & Vaccines
HIV/AIDS US HISTORY
• 2013
Loss of core caregivers
Less providers entering the field
Public apathy continues
Affected apathy increasing
No $ despite HCV emphasis
Cure and vaccines ? closer
 Treatment as prevention
- Community viral load
Global summary of the AIDS epidemic 
2011
Number of people
living with HIV
Total
Adults
Women
Children (<15 years)
People newly
infected
with HIV in 2011
Total 2.5 million [2.2–2.8 million]
Adults 2.2 million [2.0–2.4 million]
Children (<15 years) 330 000 [280 000–380 000]
AIDS deaths in 2011
*Total 1.7 million [1.6 million–1.9 million]
Adult 1.5 million [1.3 million–1.7 million]
Children (<15 years)
230 000 [200 000–270 000]
*Total 2.2 million deaths in 2005
34.2 million [31.8–35.9 million]
30.7 million [28.6 –32.2 million]
16.7 million [15.7 –17.8 million]
3.4 million [3.1 million–3.9 million]
>16.6 million children have lost their parents
Global estimates for adults and children  2011
People living with HIV
34.2 million [31.8 – 35.9 million]
New HIV infections in 2011
2.5 million [2.2 - 2.8 million]
Deaths due to AIDS in 2011
1.7 million [1.6 – 1.9 million]
Adults and children estimated to be living with HIV  2011
Eastern Europe
Western &
Central Europe & Central Asia
860 000
1.5 million
[780 000 – 960 000][1.3 million – 1.8 million]
North America
1.4 million
East Asia
[1.1 million – 2.0 million]
830 000
Middle East & North Africa
Caribbean
230 000
[200 000 – 250 000]
Latin America
1.4 million
[1.1 million – 1.7 million]
[590 000 – 1.2 million]
330 000
[250 000 – 450 000]
South & South-East Asia
4.2 million
Sub-Saharan Africa
[3.1 million – 4.7 million]
[22.2 million – 24.7 million]
Oceania
23.5 million
53 000
[47 000 – 60 000]
Total: 34.2 million [31.8 million – 35.9 million]
Estimated number of adults and children
newly infected with HIV  2011
Eastern Europe
Western &
Central Europe & Central Asia
30 000
[21 000 – 40 000]
North America
58 000
170 000
[110 000 – 220 000]
[21 000 – 130 000]
Middle East & North Africa
Caribbean
13 000
[9700 – 16 000]
Latin America
86 000
[52 000 – 140 000]
East Asia
89 000
[44 000 – 170 000]
39 000
[29 000 – 60 000]
South & South-East Asia
300 000
Sub-Saharan Africa
1.7 million
[1.6 million – 1.9 million]
[220 000 – 340 000]
Oceania
2900
[2200 – 3800]
Total: 2.5 million [2.2 million – 2.8 million]
Estimated adult and child deaths from AIDS  2011
Eastern Europe
Western &
Central Europe & Central Asia
9300
[8300 – 10 000]
North America
20 000
90 000
[74 000 – 110 000]
East Asia
[16 000 – 27 000]
60 000
Middle East & North Africa
Caribbean
10 000
[8200 – 12 000]
Latin America
57 000
[35 000 – 86 000]
[42 000 – 83 000]
25 000
[17 000 – 35 000]
South & South-East Asia
270 000
Sub-Saharan Africa
1.2 million
[1.1 million – 1.3 million]
[140 000 – 600 000]
Oceania
1300
[<1000 – 1800]
Total: 1.7 million [1.6 million – 1.9 million]
Children (<15 years) estimated to be living with HIV  2011
Western &
Central Europe
North America
1800
4500
Eastern Europe
& Central Asia
17 000
[14 000 – 21 000]
[1400 – 2100]
[4000 – 5800]
Middle East & North Africa
Caribbean
18 000
[15 000 – 21 000]
Latin America
40 000
[29 000 – 54 000]
East Asia
16 000
[11 000 – 22 000]
19 000
[12 000 – 26 000]
South & South-East Asia
180 000
Sub-Saharan Africa
3.1 million
[2.8 million – 3.4 million]
[100 000 – 230 000]
Oceania
3600
[2800 – 4600]
Total: 3.4 million [3.1 million – 3.9 million]
Estimated number of children (<15 years)
newly infected with HIV  2011
Eastern Europe
Western &
Central Europe & Central Asia
<200
[<200]
North America
<100
1700
[1400 – 2200]
East Asia
[<200]
2000
Middle East & North Africa
Caribbean
1100
[<1000 – 1400]
Latin America
2000
[<1000 – 3900]
[<1000 – 4100]
3100
[2100 – 4500]
South & South-East Asia
21 000
Sub-Saharan Africa
[14 000 – 27 000]
[250 000 – 350 000]
Oceania
300 000
<500
[<200 – <500]
Total: 330 000 [280 000 – 380 000]
Over 7000 new HIV infections a day in 2011
 About 97% are in low and middle income countries
 About 900 are in children under 15 years of age
 About 6000 are in adults aged 15 years and older, of
whom:
─ almost 47% are among women
─ about 41% are among young people (15-24)
2011 global HIV and AIDS estimates
Children (<15 years)
Children living with HIV
3.4 million [3.1– 3.9 million]
New HIV infections in 2011
330 000 [280 000 – 380 000]
Deaths due to AIDS in 2011
230 000 [200 000 – 270 000]
Over 7000 new HIV infections a day in 2011
 About 97% are in low and middle income countries
 About 900 are in children under 15 years of age
 About 6000 are in adults aged 15 years and older, of
whom:
─ almost 47% are among women
─ about 41% are among young people (15-24)
HIV /AIDS Epidemiology – 2010
USA
•
•
•
•
~50,000 new infections / yr. in USA
19343 Deaths in USA in 2010
891,843 adults living with HIV in USA
Estimated 252,000-312,000 infected
in USA that are unaware of their status
 Epidemic of the poor and marginalized:
 African Americans (AA)
 Hispanics
 MSM
 There is a new resurgence in :
 MSM
 AA
 The prevalence of infected living is increasing as
the number of new infections is > deaths
 The number of heterosexuals reported is
increasing (Reporting)
Utah
People Living with HIV/AIDS 2011
HIV (including AIDS
# 2,614
92.8/100,000
AIDS Diagnosis
# 1,410
50.1/100,000
People living with HIV (including AIDS) had  2.2% from 2010-2011
UDOH
New HIV Infections – Utah
2010 2011
• HIV infection (including AIDS):
• AIDS Diagnoses:
Modified from UDOH by KMR
86
23
94
31
HIV/AIDS Infection Rates 20022011 UTAH
UDOH-2012
Utah Trends
• New HIV infection rates:
  7% from 2010-2011
 32% from 2009 to 2010
 38% from 2006 to 2010
• New AIDS diagnosis rates:
 22% from 2010 to 2011
 32% from 2009 to 2010
 44% from 2006 to 2010
Modified from UDOH by KMR
New HIV Infections in Utah 2010^2011*
• 86%^ (83%)* were among males
• Highest rate overall was in males 40 – 44 y/o^
(20-29 y/o)*
 Followed by males 35 – 39 y/o^ (30-39 y/o)*
• Highest rate among females was in 40 – 44 y/o^
(20-29y/o)*
 Followed by 30 – 34 y/o^ (30-39y/o)*
Modified from UDOH by KMR
New HIV Infections in Utah
2010-2011 Race / Ethnicity
•
•
•
•
61% White
30% Hispanic
7 % Black
2% Unknown Race
or Ethnicity
•
•
•
•
•
62% White
23% Hispanic
4.2% Black
4% Multi/Other
6% Asian
Modified from UDOH by KMR
New HIV Infections in Utah
2010-2011* Risk of Transmission
•
•
•
•
•
•
61%
19%
6%
4%
10%
MSM (male to male sexual contact)
50%*
MSM + IDU (intravenous drug use) 17%*
Heterosexual
16%*
IDU
7.4%*
Unidentified risk
4.3%*
No Reported Risk Factor
5.3%*
Modified UDOH by KMR
Diagnosed Cases
25
20
15
10
5
0
1
2
2010*
2009
2008
2007
2006
250
2005
2004
2003
2002
2001
2000
1999
1998
1997
1996
1995
1994
1993
1992
1991
1990
1989
1988
1987
1986
1985
1984
1983
1982
Diagnosed Cases
HIV Infections, AIDS, and Deaths,
Utah
300
HIV Infection
200
150
100
50
0
Clinic 1A
New Patient Demographics
Age
13-29
30-39
40-49
50-60
>60
Gender
Male
Female
Trans
2007 (170)
2008 (158)
2009(166)
2010 (128)
27%
24%
32%
15%
1%
28%
47%
27%
13%
1%
23%
30%
32%
13%
1%
32%
27%
29%
9%
2%
83.5%
16.5%
84%
16%
1%
84%
15%
85%
14%
1%
CM Snyder,PA-C
Clinic 1A
New Patient Demographics 2002 / 2009
Race
African American / Black
Caucasian / White
Hispanic
Asian / Other
Payer Source
Self / Ryan White PCA
Private
Medicaid & / or Medicare
Utah State Prison
2010 (129)
7%
(9)
60%
(78)
30% (39)
3%
(3)
2002 (121)
6%
77%
7%
11%
48%
36%
13%
2%
45%
36%
16%
4%
CM Snyder, PA-C
(62)
(47)
(15)
(3)
Clinic 1A
New Patient Demographics 2002 - 2010
Newly DX’d
HIV not AIDS
AIDS
2002 (n=121)
2009 (n=166)
59
75
45
90
107
57
49%
62%
37%
CM Snyder, PA-C
54%
64%
35%
2010 (n=129)
64
80
48
50%
62%
37%
CURRENT PEDIATRIC AND YOUTH
HIV/AIDS
UNIVERSITY OF UTAH-5/2011
• Peds ID (<18) = 26 patients
• Clinic 1A (18-24 years of age) = 42
patients
• Grand total of pts seen from ages 0-24 =
68 patients
White M 2011
PEDS & YOUTH HIV/AIDS UU 5/2011
Gender
Male
Female
Transgendered
Total
Peds ID
15
11
0
26
Clinic 1A
36
5
1
42
Total
51
16
1
68
White M & Pavia A 2011
PEDS AND YOUTH HIV/AIDS UU
5/2011
RISK
N= 68
NOTES
PERINATAL
27
26 PEDS, 1 CL1A
MSM
28
MSM & IDU
8
HETEROSEXUAL
4
UNKNOWN
1
Meredith White & Andy Pavia
PEDS HIV/AIDS - UU – 5/2011
N= 26
%
<2
1
4
2-4
4
15
5-11
14
54
12-17
7
27
FOREIGN
BORN
18
69
ADOPTED
15
58
REFUGEE
3
12
WHITE
3
12
HISPANIC
4
15
BLACK
19
73
AGE
Meredith White & Andy Pavia
MTCT
• HIV testing should be a routine part of
medical care unless the yield of screening is
<1/1000
• Opt out, not in!
• Utah Health Code – Title 26-6-18
• Minor consent law as related for treatment of
sexually transmitted infections
WHEN TO TREAT?
IS GETTING
EARLIER
LATER
HIT EARLY
HIT HARD
1994
HARM OF UNCONTROLLED VIREMIA
MORE AND BETTER RX OPTIONS
POTENCY,TOLERABILITY,
DURABILITY, SIMPLICITY
ABILITY TO SUPPRESS MULTIDRUG R
LESS EMERGING RESISTANCE
DRUG TOXICITY
PRESERVATION OF RX
COST
KMR
WHEN TO START TREATMENT
AIDS/CD4<350μ/L
TREAT AI
CD4 350-500 μ/L
TREAT
AII
CD4>500μ/L
TREAT
BIII
Pregnancy
HIV associated nephropathy
HBV/HCV
Opportunistic infections
>age 60
Active or high risk CVD
Symptomatic Primary infection
High risk of transmission
TREAT IF ANY OF THESE CO-EXIST
AI
Context
Of
Patient*
The patient must be willing and able to commit! AIII
*Contextual
Medicine
CDC 2012
Current ARV Medications
NRTI
PI
Fusion Inhibitor
 Abacavir (ABC)
 Didanosine (ddI)
 Emtricitabine (FTC)
 Lamivudine (3TC)
 Stavudine (d4T)
 Tenofovir (TDF)
 Zidovudine (AZT,
ZDV)
 Atazanavir (ATV)
 Darunavir (DRV)
 Fosamprenavir (FPV)
 Indinavir (IDV)
 Lopinavir (LPV)
 Nelfinavir (NFV)
 Ritonavir (RTV)
 Saquinavir (SQV)
 Tipranavir (TPV)
 Enfuvirtide (ENF, T-20)
CCR5 Antagonist
 Maraviroc (MVC)
Integrase Inhibitor
 Raltegravir (RAL)
 Elvitegravir (Quad)
NNRTI
 Efavirenz (EFV)
 Etravirine (ETR)
 Nevirapine (NVP)
September
2010
Rilpivirine
(RPV)
 = FDA approved for pediatric treatment
AETC National Resource Center,
www.aidsetc.org
61
TREATMENT AS PREVENTION
PRE - EXPOSURE
PROPHYLAXIS PrPEP
– iPrEX study
•
•
•
•
•
Multinational
Tenofovir/emtcitrabine daily
MSM discordant couples
44% in HIV acquisition
Adherence mattered- 50%
• CDC recommends an an prevention measure
– $$$ payment varies
Epidemiology of AIDS in the
Aged
 New AIDS cases diagnosed in persons >50 yrs.
remains constant about 10%
 The cumulated numbers of patients >50 yrs. increased
5-fold from 1990-2001.
 In 2000, 19% of the US patients living with AIDS were
>50 yrs. (9% were younger when originally Dx)
 Older patients are more likely than younger patients to
present late for care
 Older patients were more likely to be diagnosed when
presenting with another illness ( OR 2.29)
AGING AND AIDS
IDU’s are
getting older
AGING
HIV
COMORBIDITY
&
DRUG TOXICITY
HIV RX
HAART
“Age at
seroconversion
is getting
older” 2010
Justice A CROI 2008 Session 105
HIV/AIDS In The Older Patient
# OF HEALTH CONDITIONS
THAT CAN’T BE CURED
HIV
(VIRUS & RX)
AGE
(CHRONOLOGICAL
MULTIMORBIDITY
CKD
METABOLIC
DIABETES
OBESITY
OSTEOPOROSIS
CVD
MALIGNACIES
COPD
NEUROCOGNITIVE
HEPATITIS
HYPERTENSION
FRALITY
MAKE MORBIDITY AND
MORTALITY WORSE THAN
EACH PIECE
Epidemiology of AIDS in the
Aged- Risk
• Less prevention messages
– Patient denial to risk
– Provider denial of risk
• Perceived less access to testing
• Availability of impotence treatments
• Biological factors (vaginal Dryness, etc.)
Natural History of HIV Infection
in Older Patients2
• Older age at seroconversion is associated with
decreased ability of the immune system to respond.
– faster progression to AIDS and death
– a more rapid decline in CD4 cells1.
– A higher viral load
– Lack of recognition of the diagnosis
1 Chiao EY Ries KM CID 1999; 2. Most
data pre HAART
Older Patients and HAART
(Highly Active Antiretroviral Therapy)
• With HAART the risk of progression to AIDS or death is
more similar to the younger patients
• The increase in CD4 cells is less in the older patient and
occurs more slowly
• The decrease in viral load was more rapid in the older
patients
– Better adherence*
– Less treatment interruption
*Hinkin CH et al Aids 2004
HIV AND AGING
HIV and aging both associated with early
senescence marked by:
›
›
›
›
›
›
Low levels of CD28 T-cell markers
Shortened Telomere levels
Increased mortality
Faster disease progression
Increased IL6/TNF- associated with bone loss
Persistent infection with either HIV or CMV causes senesce of
the immune system
May be mitigated by adding telomerase
› Small molecule telomerase activators (e.g. TAT2)
› ? Gene therapy
Effros R et al CROI 2008 105
HIV AND AGING
• Virologic response to HAART is later
• Increased odds ratio of being frail*
– Comparing HIV+ and HIV- ( MACS)
Years of HIV
0-4
4-8
8 - 12
OR of Frailty
3.4 (3.1-9.1)
13 (6.6-25)
15 (7.6-25)
“A 65 Y/O HIV- has a similar frailty as a 55 Y/O
HIV + If positive 0 - 4-yrs”
Ledergerber B CROI 2008 108
HIV AND AGING
PHARMACOLOGY
• KIDNEYS
– Age related changes in Clcr is variable
– Need to look at GFR
• LIVER
– Cirrhosis - blood flow so  1st pass effect
• ~0.5-1.5 % in blood flow/year >age 23
–  hepatocytes may  CYP 2C and CYP 2D
–  hepatocytes effect on CYP4A is variable
– Phase 2 enzymes are well preserved
Flexner C CROI 2008 106
HIV AND AGING
CO-MORBIDITIES
 Cardiovascular Disease
› Fixed- Sex ,FHx, Prior Hx CVD, Age
› Changeable- DM, Smoking etc
 Metabolic
› Similar to general population
 Body Composition
› Ex- Lipoatrophy is a part of aging as well
 Kidney
 Malignancy
 Bone- osteopenia
› Mineral density peaks ~ 30- don’t know if they ever peaked
Powderly W CROI 2008 107
CURE vs ‘FUNCTIONAL CURE’
THE BERLIN PATIENT
• Patient with leukemia
• Stem cells from a donor with CCR5 Δ32
deletion
• Leading to continued research
Cure vs. Functional Cure
The Baby? CROI-2013
• Mother found to be HIV + after birth
• Rx begun at 30 hours
• Infant positive for HIV DNA PCR and
plasma viral load
– 2-day 2
– days 7,12, 20
Rx started 30 hours
Persand D etal. CROI 2013 48LB
Cure vs. Functional Cure
The Baby? CROI-2013
• VL became undetectable (<20 copies/ml at
29 days)
• VL < 20 copies/ml on 16 measures Months 126
• Rx stopped at 18 months
Interesting!
• VL 1 copy/ml at 24 months
Why?
– No replication virus detected
– HIV AB negative
Persand D et al. CROI 48LB 2013
Atlanta
Can Functional Cure be Explained?
Central Memory T Cells (TCM)
• “--What happens to TCM in the context of HIV
infection may be the most important
determinant of who you’ll be able to cure and
a patients long term outcome.”
• Were the child’s TCM cells protected by early
Rx?
• Other studies show that there is a subset of
patients that do not progress in spite of high
VL may have less infection of the T CM cells
Deeks CROI 2013
ACA
Psychological Stress
Stigma
Low self esteem
Rejection
Disclosure
Prevention
Rx is
prevention!
10
Hepatitis C
&
20
interventions
Substance Abuse
Hepatitis
Hepatitis
BB
CURE
Neuro\cognitive
VACCIN
E
HIV/AIDS
HIV/AIDS
Diabetes
Hypertension
Hyperlipidemia
Hypogonadism
Neuropathy
Cancers
Strokes
Heart Attacks
OI’s
OI’s
Tumors
Tumors
Women
Pregnancy
Aging
K Ries 2013Version
Major Mental
illness
Socioeconomic Issues
Poor
Homeless
Unemployed
Uninsured
Underinsured
Incarcerated
The Ever Changing Epidemic
The First Wave
Gay white educated males
Survival very short, Big Die Off.
The Second Wave
Behavior changes decreased transmission
The Third Wave
New generation that has not experienced the first wave.
Transmission going up. New Treatments. Increasing STDs.
Methamphetamines. New sexual revolution. “Freedom”
Resistant HIV.
The Fourth Wave
New HIV / AIDS Strategy
The “C” word: Cure
CM Snyder, PA-C