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

PhysiciansAdvanced practice nursesNursesPhysician assistantsPharmacistsOral health professionalsOther healthcare professionals, including medical case managersEducators/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 mini-

residencies• 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 2 3 4

25%

33%31%

11%

1. Talking on the phone while driving.

2. Texting on the phone while driving.

3. Both 1 and 24. I plead the 5th!

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

67%

0%

33%

0%

1. A retrovirus2. A bacteria3. A virus4. A mutated cell

What does HIV do?

1 2 3 4

8%

92%

0%0%

1. Infects human cells displaying CD4 (Helper-Inducer T-lymphocytes, and a few more)

2. Integrates itself into the host chromosome3. Directs the cell to make more.4. All of the Above

HIV comes from…

1 2 3 4

3%

23%

3%

71%

1. Vaccine trials in Africa2. Chimpanzees in Africa3. A CIA plot4. Mutation of a human herpes virus

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

HIV RNA

HIV DNA

HIVNucleus

Host Cell Non-Nucleoside RTI

Protease Inhibitors

Nucleoside Analogue RTI

RT

Entry Inhibitors

DHS/PP

Entry Inhibitors

Reverse Transcriptase Inhibitors

Intergrase InhibitorRaltegravir (RAL) Isentress (2007)

Protease Inhibitors

Treatment for HIV-HAARTAntiretroviral medications—6 classes, 32 different medications:

Nucleoside Reverse Transcriptase InhibitorsAZT, 3tc, d4t, abacavir, DDI, tenofovir, emtricitabine

Non-Nucleoside Reverse Transcriptase InhibitorsNevirapine, efavirenz

Protease InhibitorsKaletra, Reyataz, Invirase, Crixivan, Norvir, Agenerase, Viracept

Fusion InhibitorsFuzeon

Entry InhibitorsSelzentry

Integrase Inhibitors Isentress

In a healthy person the number of CD4 cells is…

1 2 3

12%

64%

24%

1. 100 - 3002. 300 - 7003. 700 – 1500

If you are infected with HIV other people can tell?

1 2

95%

5%

1. True2. False

• 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).

Viral Load Test

People infected with HIV get sick and die quickly

1 2

97%

3%

1. True2. False

Which person did NOT die from AIDS?

1 2 3 4 5 6

0%

89%

3%3%3%3%

1. Rock Hudson2. Tupac Shakur3. Anthony Perkins4. Freddie Mercury5. Eazy E.6. Robert Reed

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

0%3%

0%

8%

87%

0%3%

1. Sex2. Injection Drugs3. Sharing toothbrushes4. Drinking glasses5. Childbirth6. 1, 2, & 5.7. 1, 2, & 3.

HIV 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).

Vertical Transmission

Exposed Infant

• Baby born to an HIV positive mother, does not necessarily mean the baby has the infection.

A discordant couple is

1 2 3 4

6%12%

79%

3%

1. Couples who fight a lot2. 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

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

• TimelineTransmission of the virus ------------ 2-3 weeks.Acute HIV syndrome--------- 2-3 weeksSeroconversion/ 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 CategoriesAA BB CC

CD4CD4 Asymptomatic PGL Asymptomatic PGL or Acute HIVor Acute HIV

SymptomaticSymptomatic

(not A or C)(not A or C)AIDS AIDS

indicator indicator conditioncondition

>500>500

(>29%)(>29%)A1A1 B1B1 C1C1

200-499200-499

(14-28%)(14-28%)A2A2 B2B2 C2C2

< 200< 200

(< 14%)(< 14%)A3A3 B3B3 C3C3

HAART Stands for Highly Active Anti Retroviral Therapy

1 2

9%

91%1. True2. False

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

Strong: 55% of panelModerate: 45% of panel

Favor: 50% of panelOptional: 50% of panel

500

350

Strongly Recommend

Recommend

Consider

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

52%

30%

6%3%

9%

1. None2. 5,0003. 10,0004. 50,0005. >75,000

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