Pacific AIDS
Education &Training Center
San Joaquin Valley
Local Performance Site
Andrés E. Alba Program Manager
UCSF Fresno Family and Community Medicine
Norma Sanchez – Fresno County Department of Community
Health, Communicable Disease Division
What are we (who am I)?
• The AIDS Education and Training Centers (AETC) Program of the Ryan White
CARE Act currently supports a network of 11 regional centers and more than
130 local performance sites (LPS). The AETCs serve all 50 States, the District of
Columbia, the Virgin Islands, Puerto Rico, and the six U.S.-affiliated Pacific
Jurisdictions
• The AETC Program is administered by the Health Resources and Services
Administration (HRSA), HIV/AIDS Bureau
What do we do?
• The AETC conducts targeted, multi-disciplinary
education and training programs for
healthcare providers treating persons with
HIV/AIDS and other infectious diseases
What is our Mission?
• To improve the quality of life of
patients living with HIV/AIDS
through the provision of high
quality professional education
and training
Who do we train?
Providers who serve minority populations, the
homeless, rural communities, or incarcerated
persons; community and migrant health centers,
and Ryan White CARE Act-funded sites
Physicians
Advanced practice nurses
Nurses
Physician assistants
Pharmacists
Oral health professionals
Other healthcare professionals, including
medical case managers
Educators/Teachers
What type of trainings do we offer?
• Lectures and didactic seminars
• Workshops, seminars and hands-on clinical experience
• Local clinical consultation on all aspects of managing
patient care
• Intensive clinical rotations, preceptorships and miniresidencies
• Technical assistance in quality HIV care
• Training activities are based upon
assessed local needs
* Since 1991, the AETC’s have sponsored
more than 700,000 trainings Nationally.
San Joaquin Valley (SJV) Local Performance Site
• Service 6 Counties throughout Central Valley
– Merced
– Madera
– Fresno (UCSF Fresno*)
– Kings
– Tulare
– Kern
Local Resources
•
•
•
•
•
•
•
SJV AETC Medical Director – Ivan Gomez, MD
Specialty Clinic Medical Director – Simon Paul, MD
Faculty and Chief of F.M. – Roger Mortimer, MD
I.D. Fellowship Director – Naiel Nassar, MD
HIV Fellow – Hugh Yang, DO
SJV AETC Program Manager – Andrés E. Alba
Communicable Disease Specialist with Fresno County – Norma Sanchez
1992 Facts
• The people who are starting college this fall were
born in 1992.
• They are too young to remember the space shuttle
blowing up.
• The CD was introduced two years before they were
born.
• They have always had an answering machine.
• They have always had cable.
1992 Facts
• Jay Leno has always been on the Tonight
Show.
• Popcorn has always been microwaved.
• They never took a swim and thought about
Jaws.
• They don't know who Mork was or where he
was from.
1992 Facts
• They never heard: 'Where's the Beef?', 'I'd
walk a mile for a Camel ' or 'de plane Boss, de
plane'.
• McDonald's never came in Styrofoam
containers.
• They don't have a clue how to use a
typewriter.
• Their lifetime has always included AIDS.
HIV 101
How many of you in the last 30 days
have done illegal activities?
1. Talking on the
phone while
driving.
2. Texting on the
phone while
driving.
3. Both 1 and 2
4. I plead the 5th!
33%
31%
25%
11%
1
2
3
4
Key Terms
•
•
•
•
•
•
•
HIV—Human Immunodeficiency Virus
AIDS—Acquired Immunodeficiency Syndrome
Transmission
HIV Antibody Testing
CD4 Cell Count and Percentage (T-Lymphocytes)
Viral Load/Viral Burden
Resistance Testing
– Genotype
– Phenotype
– Trophile Assay
Key Terms
• Antiretroviral Therapy
– HAART—Highly Active Antiretroviral Therapy
– Classes of Medications
– Medication Regimen
– Adherence
– Viral Resistance
• Treatment Guideline Changes
• HIV Lifecycle
What is HIV?
1.
2.
3.
4.
A retrovirus
A bacteria
A virus
A mutated cell
67%
33%
0%
1
2
0%
3
4
What does HIV do?
1. Infects human cells displaying CD4 (HelperInducer T-lymphocytes, and a few more)
2. Integrates itself into the host chromosome
3. Directs the cell to make more.
4. All of the Above
92%
8%
0%
1
2
0%
3
4
HIV comes from…
71%
23%
1.
2.
3.
4.
3%
Vaccine trials in Africa
Chimpanzees in Africa
A CIA plot
Mutation of a human herpes virus
1
3%
2
3
4
Origins
• The first leap happened
between 1919 and 1945.
• Butchering of
chimpanzees for ‘bush
meat’ is the presumed
mechanism.
Worobey, Nature 2008; 455:661-664
To Demonstrate cross-over from one
species (Chimpanzees—SIV) to another
(Humans—HIV): what to look for?
•
•
•
•
•
similar genome organization
phylogenetic relatedness
prevalence in the natural host
geographic coincidence
plausible routes of transmission
Origins
• HIV-1 is a descendant of
SIV from the
chimpanzee (Pan
troglodytes).
• The jump to humans
has happened at least 3
different times.
• Most human disease
comes from group M,
clade B.
Wain et al. Mol Biol Evol, (2007) 24 (8): 1853
HIV: Antiretroviral Therapy
Nucleoside Analogue RTI
Entry Inhibitors
RT
HIV
RNA
HIV
DNA
HIV
Non-Nucleoside RTI
Host
Cell
Nucleus
Protease
Inhibitors
DHS/P
Entry Inhibitors
Reverse Transcriptase Inhibitors
Intergrase Inhibitor
Raltegravir (RAL) Isentress (2007)
Protease Inhibitors
Treatment for HIV-HAART
Antiretroviral medications—6 classes, 32 different medications:
Nucleoside Reverse Transcriptase Inhibitors
 AZT, 3tc, d4t, abacavir, DDI, tenofovir, emtricitabine
Non-Nucleoside Reverse Transcriptase Inhibitors
 Nevirapine, efavirenz
Protease Inhibitors
 Kaletra, Reyataz, Invirase, Crixivan, Norvir, Agenerase, Viracept
Fusion Inhibitors
 Fuzeon
Entry Inhibitors
 Selzentry
Integrase Inhibitors
 Isentress
In a healthy person the number of CD4
cells is…
64%
1. 100 - 300
2. 300 - 700
3. 700 – 1500
24%
12%
1
2
3
If you are infected with HIV other
people can tell?
1. True
2. False
95%
5%
1
2
Viral Load Test
• Also called an RNA PCR. This test measures
the number of copies of the HIV virus present
in the blood.
– Ranges from undetectable (<50 to millions).
People infected with HIV get sick and
die quickly
1. True
2. False
97%
3%
1
2
Which person did NOT die from AIDS?
1.
2.
3.
4.
5.
6.
Rock Hudson
Tupac Shakur
Anthony Perkins
Freddie Mercury
Eazy E.
Robert Reed
89%
0%
1
2
3%
3%
3%
3%
3
4
5
6
Epidemiology
What is Incidence?
Incidence is a measure of the risk of developing some
new condition within a specified period of time.
Simply it is the number (#) of new cases during some
time (t) period, it is better expressed as a proportion
or a rate with a denominator
What is Prevalence?
The total number of cases of the disease in
the population at a given time, or the total
number of cases in the population, divided by
the number of individuals in the population.
a as the number of individuals in a given population with the disease at a given time, and b
as the number of individuals in the same population at risk of developing the disease at a
given time, not including those already with the disease
Epidemiology
•
•
•
•
•
Incidence remaining the same.
Prevalence increasing (why?)
40-60,000 new HIV cases per year in the USA.
900,000 cases of HIV/AIDS in USA
1/3 don’t know status.
Epidemiology
• 2008—CDC adjusted its estimates of new HIV
infections
– New technologies
– Previous estimations placed new infection rate
at 40,000 persons per year
– Dramatic decrease in numbers from over
130,000 in 1980s to ~50,000 in the 1990s
– In 2006, CDC estimates 56,000 people were
infected with HIV
CDC. 2009
HIV No Name Reporting
• 2004 – only reported with first letter of last
name, date of birth, and last 4 digits of Social
Security
• 2007 – CDC recommends names reporting
• CA – one of the last states to report by name
• Now HIV and AIDS reported by names
U.S. Demographics and
Spread of AIDS
National Statistics
CDC, 1997
National Statistics
CDC, 1997
National Statistics
CDC, 1997
National Statistics
CDC, 1997
National Statistics
CDC, 1997
Fresno Stats
Transmission
HIV can be transmitted via
1.
2.
3.
4.
5.
6.
7.
Sex
Injection Drugs
Sharing toothbrushes
Drinking glasses
Childbirth
1, 2, & 5.
1, 2, & 3.
87%
8%
0%
1
3%
2
0%
3
3%
4
0%
5
6
7
HIV Transmission
Vertical Transmission
• Also called Mother to Child Transmission (MTCT).
• Transmission of the virus to the child either:
– During pregnancy – 25%.
– Intrapartum – 75%.
– Post Partum – breast feeding increases the risk of
transmission by 14% (26% risk if newly infected
mother).
Exposed Infant
• Baby born to an HIV positive mother, does not
necessarily mean the baby has the infection.
A discordant couple is
1. Couples who fight a lot
2. Couples who can’t agree
about birth control
methods
3. Couples where one
partner is HIV + and one
partner is HIV –
4. Couples who play
musical instruments
badly
79%
12%
6%
1
3%
2
3
4
HIV Infection
Sequence of events:
• HIV is transmitted with extension to regional
lymph tissue (within the first few days of
exposure).
HIV Infection
Massive viremia – billions of virions produced
every day.
• Transmission risk is high – asymptomatic +
high viremia.
• Acute HIV syndrome may be seen – but
difficult to diagnose and often missed.
Acute HIV Syndrome
•
•
•
•
•
•
•
•
Fever
Lymphadenopathy
Pharyngitis
Rash (morbilliform)
Myalgia
Headache
N/V/D
Occurs 2-4 weeks after infection and resolves in 1-4
weeks.
HIV Infection
• Seroconversion occurs 3-4 weeks after
transmission but may take up to 6 months.
• For pregnant mothers - Implications for testing
- If negative in the first trimester, may want to
retest in 3rd trimester if high risk.
HIV Infection
• Timeline
Transmission of the virus
------------ 2-3 weeks.
Acute HIV syndrome
--------- 2-3 weeks
Seroconversion/ Asymptomatic disease
-------- Average 5-8 years.
Symptomatic disease/AIDS
HIV Infection
CD4 cells destruction – average 50/year.
• In some clients this may be slower – these are
called long term non-progressors.
•In some the progression is much faster and
and they will advance to an AIDS diagnosis in
3-5 years.
HIV Infection
• Progression to AIDS is faster in children–
usually 5 years or less.
• Less HAART medication options than in the
adult.
• Prevention is therefore very important.
Clinical Categories
A
B
C
CD4
Asymptomatic PGL or
Acute HIV
Symptomatic
(not A or C)
AIDS indicator
condition
>500
(>29%)
A1
B1
C1
200-499
(14-28%)
A2
B2
C2
< 200
(< 14%)
A3
B3
C3
HAART Stands for
Highly Active Anti Retroviral Therapy
1. True
2. False
91%
9%
1
2
What’s the big deal about HAART???
Can we treat our way out of the epidemic?
• Theoretically, yes:
– Perinatal transmission rate = 30%
• Sexual transmission rate=0.5%
– Pre and post-exposure prophylaxis to HIV infected
mothers/fetus lowers infection to less than 1/100
• Similar effectiveness would lower sexual transmission to
0.0002 or 1/5,000, probably enough to make R<1!
– The problems are practical:
• Identifying all infected
• Treating large numbers of patients
• Treating un-infected persons for the purpose of prevention
– Treat breastfeeding moms?
• Currently for every 1-2 persons starting treatment, 5 new
infections
Adherence
With poor adherence, there will be viral evolution
and virologic failure. But this does not reflect how
well HAART works; it reflects drug-taking behavior.
With good adherence, patients do not experience
spontaneous virologic failure, indicating that clinically
significant viral evolution is not occurring.
Robert F. Siliciano, MD, PhD
Adherence
• Adherence is taking the correct medication, at the
correct time and in the correct way.
• Missing doses of HIV medication results in a lower
blood level of the medication.
• The lower blood level of the medication allows
greater replication of the virus.
• At higher viral blood levels, there will be more viral
mutations which can lead to drug resistance.
• Optimal suppression is considered to occur at 95%
adherence level or above.
Resistance is Futile
Drug Resistance
• The ability of the virus to multiply in spite of the
presence of the antiretroviral drug.
• Drug resistance -failure- requires changing to less
desirable regimens (increased pill burden and more
frequent dosing).
• Patients with drug resistance to 2 classes will have a
greater than 50% incidence of AIDS event or death,
resistance to 3 classes – an 80% greater incidence,
compared to one or no class resistance
Drug Resistance
• Drug resistance occurs due to mutations present on
the viral genetic material.
• Mutations are very common in the replication process,
up to 90% of new viruses have mutations that prevent
them from being infective. A less fit virus!
• Mutations are random and the number of mutations
occurring are proportional to the viral load.
• Certain mutations that occur can confer resistance to a
specific medication or class of medication
Drug Resistance
Resistance evaluated by :
Phenotype testing- the virus is grown in the
presence of antiretroviral medication to determine
sensitivity.
Genotype testing- the viruses genetic code is
tested to determine specific mutations which are
known to confer resistance.
DHHS Antiretroviral Therapy Guidelines: December 2009
Recommended Timing for Initiating Therapy
Consider
Favor: 50% of panel
Optional: 50% of panel
Recommend
Strong: 55% of panel
Moderate: 45% of panel
500
350
Strongly Recommend
Source: AIDS Info (www.aidsinfo.nih.gov)
Prevention of Transmission
•
•
•
•
Abstinence works
Condoms are protective
Get tested—know your status
If participating in risk behaviors, test
minimally once a year—better every six
months
Each year in the U.S., how many people
die from HIV?
1.
2.
3.
4.
5.
None
5,000
10,000
50,000
>75,000
52%
30%
9%
3%
1
2
3
4
6%
5
Opportunistic Infections
Bacterial, viral or protozoan infections seen in
patients with CD4 counts of less than 200.
This may also include some malignancies.
Opportunistic Illness (OI)
• Candidiasis (esophagus, trachea, lungs,
bronchi).
• Cervical cancer (invasive)
• Cryptococcus.
• Coccidioidomycosis (extrapulmonary).
• Cryptosporidiosis with diarrhea for > 1 mos.
Opportunistic Illness (OI)
• CMV of any organ other than lymph node,
spleen or eye.
• Histoplasmosis (extrapulmonary).
• HIV associated dementia.
• HIV associated wasting syndrome (10%
baseline)
• Isoporosis with diarrhea > 1 month.
Opportunistic Illness
•
•
•
•
•
Kaposi’s Sarcoma.
Burkitt’s Lymphoma.
Mycobacterium Avium (disseminated MAC).
Pneumocystis Carinii Pneumonia.
Progressive Multifocal Leukoencephalopathy
(PML).
Opportunistic Illness
• Salmonella Septicemia (non typhoid
recurrent).
• Toxoplasmosis of internal organ.
Questions