Butler University Physicians Assistant

Clinical Medicine Course

October 2010

Suellyn Sorensen, PharmD, BCPS

Adjunct Assistant Professor BUCOPHS

Clinical Pharmacist, Infectious Diseases – IU Hospital

Clinical Director MATEC

HIV Infection/AIDS

MATEC Indiana is a program of Clarian Health and part of the federally funded National AIDS Education and Training Centers (AETC) of Health Resources and Service Administration (HRSA). The National ATEC was established in 1988 by the Ryan White Care Act in response the HIV/AIDS Epidemic.

See www.matec.info for more information

About MATEC

Our mission is to improve access and quality of HIV/AIDS care and prevention for Indiana residents.

Our Mission

Important

We need the following from all participants:

• Sign-in on sign-in sheet that is circulating• Complete the “Immediate Post Program

Evaluation” Form • Complete the “Participant Form”

Equipment: A “clicker” and a Participant

System allows speakers to get audience input and allows the audience to see how everyone else

answered a particular question.

Audience Response System

A Practice Question:Which age range do you fall into?

1 2 3 4

0% 0%0%0%

1. 19-24

2. 25-29

3. 30-35

4. 36 or Older

1. Describe the history and progression of HIV/AIDS since first identified

2. List criteria for routine HIV screening/testing based on CDC recommendations

3. Describe the current status and characteristics of the HIV/AIDS epidemic nationally and locally.

4. List risk factors for HIV infection and explain how HIV is transmitted

5. Identify the difference between HIV and AIDS

6. Describe how HIV infection is commonly diagnosed

Learning Objectives

• HIV was first identified in the United States in 1981 after a number of gay men started getting sick with a rare type of cancer.

CDC Website:http://www.cdc.gov/hiv/topics/basic/index.htm#origin

Brief History of HIV in the United States

“Epidemics do not announce themselves but enter on cat’s paws.”

Courtesy of Brad Hare, MD & Diane Jones, RN -- UCSF Positive Health Program at SFGH

19811981

History of HIV/AIDS Summary

• 1981 – AIDS 1st reported• 1987 – Zidovudine FDA approved• 1992 – AIDS deaths exceed 200,000• 1996 – HAART standard of care

• HIV Viral Load Marker approved• 1997 – Falling number of deaths• 1998 – HAART tx complications emerge• 2001 – HIV recognized as a chronic disease• 2002 – Focus on the Global HIV epidemic• 2004 – Once daily combination formulations FDA approved• 2006 - 1st Once daily triple combination tablet FDA

approved• 2007 – 1st CCR5 receptor antagonist FDA approved• 2008 – 1st Integrase Inhibitor FDA approved

Declining Mortality Associated with Increasing Triple Combination Therapy with PIs

Palella, F.J. et al. N. Engl. J. Med. 338(13):853-860, March 26, 1998.

1,255 patients with at least one CD4 value <100 cells/mm3 6 months prior to study entry

0

10

20

30

40

1994 1995 1996 19970

1020

30

40

50

607080

90

100Therapy

with a

protease

inhibitor

(% of

patient-

days)

Deaths

per 100

person-

yearsDeaths

Use of protease inhibitors

Year

Mortality and HAART Use Over TimeHIV Outpatient Study, CDC, 1994-2003

Year

De

ath

s p

er

10

0 P

Y

Patients on HAART

Deaths per 100 PY

0

2

4

68

10

12

14

1994 1995 1996 1997 1998 1999 2000 2001 2002 200300.10.20.30.40.50.60.70.80.9

Pa

tien

ts o

n H

AA

RT

• At the end of 2006, an estimated 1,106,400 persons in the United States were living with HIV infection, with 21% undiagnosed.

• In 2006, there were 35,314 new cases of HIV/AIDS in adults, adolescents, and children diagnosed in the 33 states with long-term, confidential name-based HIV reporting.

• CDC has developed a new and innovative system designed to estimate the number of new HIV infections (or incidence) for the United States in a given year.

• Using this new technology, CDC estimates that 56,300 new HIV infections occurred in the United States each year.

HIV/AIDS Facts

CDC HIV Prevalence Estimates—United States, 2006. MMWR 2008;57(39):1073-76. HIV/AIDS in the US-CDC Fact Sheet. http://www.cdc.gov/hiv/resources/factsheets/us.htm

Spotlight on HIV/STD/Viral Hepatitis, Indiana Semi-Annual Report 2009:http://www.in.gov/isdh/files/map_cases.pdf

4043 - Persons Living with HIV/AIDS in Marion County as of June 2010

81% Male (3291)19% Female (752)

Race/Ethnicity 47% White (1916) 70% of County Population is White43% Black (1729) 26% of County Population is Black6% Hispanic (257)2% Multi-Race (107)<1% Asian (34)

HIV in Marion County

http://www.in.gov/isdh/files/At_a_Glance.pdf

http://www.stats.indiana.edu/profiles/pr18097.html

1 2 3 4

0% 0%0%0%

1. 9,798

2. 4,652

3. 1,813

4. 12,345

As of June 2010, how many people with HIV were reported to have been living in Indiana?

Routine Testing

Number HIV infected 1,039,000 – 1,185,000

Number unaware of their HIV infection 252,000 - 312,000 (24%-27%)

Estimated new infections 40,000 - 56,300 annually

Awareness of HIV Status among Persons with HIV, United States

Glynn M, Rhodes P. 2005 HIV Prevention Conference

Awareness of Serostatus Among People with HIV and Estimates of Transmission

~25% Unaware

of Infection

~75% Aware of Infection

People Living with HIV/AIDS: 1,039,000-1,185,000

New Sexual Infections Each Year: ~32,000

Accounting for: ~54% of New

Infections

~46% of New

Infections

Marks, et alAIDS 2006;20:1447-50

According to the 2006 CDC HIV Testing Recommendations, health care providers should offer routine HIV screening to patients of which age group?

1 2 3 4

0% 0%0%0%

1. Birth to Death

2. 10-35

3. 13-64

4. None of the Above

HIV Testing Recommendations

• HIV screening: all patients 13-64 yrs in all health care settings

• Repeat annually if known risk• Opt-out HIV screening • Include HIV consent with general consent

for care, written consent is not needed• Prevention counseling not required

MMWR 2006;55(RR14);1-17

• HHuman IImmunodeficiency VVirus

• HIV attacks a person’s immune system (CD4 Cells), leaving him/her vulnerable to other infections

• It is a compromised immune system that makes an HIV positive person sick, not the virus itself. HIV HIV is the virus that causes Acquired

Immune Deficiency Syndrome (AIDS)

What is HIV?

Please Reference Handout: The Basics of HIV Infection and AIDS

• Consider persons whose HIV status is negative or unknown as high risk if they have a recent history (past 6 months) of 1 or more of the following: unprotected sex with a person who is living with HIV unprotected sex in exchange for money or sex multiple (e.g., more than 5) or anonymous sex

partners multiple or anonymous needle-sharing partners a diagnosis of a sexually transmitted disease

Risk Factors

Reduce sexual risk:• Abstinence; mutual monogamy with uninfected

partner• Limited sexual contact (non-penetrative)• Condoms: correct and consistent use• Reduce number of sexual partners; talk with new

partners about risk reduction• Avoid sex if you have symptoms of an STD; notify

recent partners if you have an STD

Risk Reduction Techniques

• Do not share drug injection equipment• Needles, syringes, cotton, spoons

• If HIV+ and pregnant:• Talk to doctor about taking

antiretrovirals• Don’t breastfeed

• ALWAYS: Careful use of Universal Precautions

Risk Reduction Techniques

HIV Can ONLY be Transmitted through FOUR Body Fluids

1) Blood

2) Semen

3) Vaginal Secretions

4) Breast Milk

How do you get HIV?

These Body Fluids must then find entry into the body

1) Mucous Membrane: Anal, Oral or Vaginal Sex

2) Blood to Blood: Needle or Broken Skin, Perinatal

3) Consumption of Breast Milk

How do you get HIV?

Universal Precautions

• Universal precautions involve the use of protective barriers such as gloves, gowns, aprons, masks, or protective eyewear, which can reduce the risk of exposure of the health care worker's skin or mucous membranes to potentially infective materials.

• In addition, under universal precautions, it is recommended that all health care workers take precautions to prevent injuries caused by needles, scalpels, and other sharp instruments or devices.

Universal Precautions for Prevention of Transmission of HIV and Other Bloodborne Infections:http://www.cdc.gov/ncidod/dhqp/bp_universal_precautions.html

HIV and the Immune System

• HIV destroys CD4 positive (CD4+) T cells, which are white blood cells crucial to maintaining the function of the human immune system

• People who are not infected with HIV and generally are in good health have roughly 800 to 1,200 CD4+ T cells per cubic millimeter (mm3) of blood.

NIH Understanding How HIV Causes AIDS: http://www3.niaid.nih.gov/topics/HIVAIDS/Understanding/howHIVCausesAIDS

HIV and the Immune System

• HIV destroys CD4 positive (CD4+) T cells, which are white blood cells crucial to maintaining the function of the human immune system

• People who are not infected with HIV and generally are in good health have roughly 800 to 1,200 CD4+ T cells per cubic millimeter (mm3) of blood.

• Some people who have been diagnosed with AIDS have fewer than 50 CD4+ T cells in their entire body.

• CD4 counts measure how well a person’s body is able to fight off infection, ie. how much damage HIV has done to the immune system

NIH Understanding How HIV Causes AIDS: http://www3.niaid.nih.gov/topics/HIVAIDS/Understanding/howHIVCausesAIDS

HIV and the Immune System (2)

• A viral load test is a measurement of HIV RNA in the blood.

• This Information when used in conjunction with a person’s CD4 count is used to:

to monitor response to antiretroviral therapy to predict and monitor HIV disease progression

• There are several different types of viral load tests, PCR (polymerase chain reaction) and bDNA (branched DNA) are two of the most common.

The AIDS InfoNET. Fact Sheet. Viral Load Tests.http://www.aids.org/factSheets/125-Viral-Load-Tests.html

CD4 Count

• Measures immunologic status of the patient• Performed at time of diagnosis and q 3-6 months

thereafter• Normal CD4 count is 800-1000 cells/mm3

• CD4 count < 200/mm3 is associated with the development of OIs and meets the case definition for AIDS

• A substantial decrease in CD4 is considered to be >30% decrease from baseline for absolute #s

• Expect an increase of > 100-200 cells/mm3/yr but response is variable

HIV/RNA Assay

.

• Directly measures the amount of HIV virus in the blood

• Predictive of disease progression and used to monitor response to therapy

• Performed at time of diagnosis and q 3-4 months thereafter

• Performed immediately before initiation of therapy and 2-8 weeks after

• Expect 1 log decrease at 2-8 wks and undetectable (<50 copies/ml) by 16-24 wks

• HIV Antibody Testing has two stages

• First Stage: Antibody Detection. Enzyme Immunoassay (EIA)/Enzyme-Linked Immunosorbent Assay (ELISA) are screening tests that detect HIV antibodies

• Blood

• Oral Fluid

• Urine

• Second Stage: Confirmatory Western Blot

HIV Antibody Tests

• Western Blot is the “Gold Standard” when confirming a person’s HIV status

• A person CANNOT be given an HIV diagnosis from an EIA/ELISA without a confirmatory Western Blot Test or a Viral Load

Western Blot

The Western Blot. Davidson College: Molecular Biology Department. Charles Wood. [Online]. 2009 Cited October 2009 a

Available from URL: http://www.bio.davidson.edu/Courses/Molbio/MolStudents/spring2003/WoodC/western.html

Virus in Blood

Antibodies Detected

Window PeriodWindow Period

Infection

3 – 6 weeks (most people)W/in 3 months = >99% of people infected

Window Period

PAETC HIV/AIDS Basic Training Curriculum Guide June 2007.

• Acquired Immune Deficiency Syndrome

• According to Webster’s Medical Dictionary , a syndrome “is any group of symptoms commonly occurring together”

• An AIDS diagnosis is made using a specific set of criteria created by the CDC, which includes a variety of opportunistic infections and cancers. This is why it is considered a syndrome.

What is AIDS?

• Opportunistic Infection (OI): HIV infection can weaken a person’s immune system to the point that it has difficulty fighting off certain infections. These types of infections are known as opportunistic infections because they take the opportunity a weakened immune system gives to cause illness.

• Opportunistic infections are CDC-defined AIDS indicator illnesses, which means that an HIV-infected person receives a diagnosis of AIDS after the development of 1 of them.

Opportunistic Infections

CDC Integrated Epidemiologic Profile for HIV/AIDS Prevention and Care Planning--Louisiana, 2002 http://www.cdc.gov/hiv/topics/surveillance/resources/guidelines/epi-guideline/la_supp/glossary.htm

Why do opportunistic infections occur in people with HIV/AIDS?

• Over time, HIV (the virus that causes AIDS) attacks and weakens the immune system. The body then loses its ability to attack germs. At that point, infections that people with healthy immune systems usually resist can take advantage of the body’s weakened state and cause infections in people with AIDS ( a result of HIV infection)

CDC. MMWR, 2002; vol. 51, no. RR-8. “Guidelines for Preventing Opportunistic Infections Among HIV-Infected Persons.”

Decreased Rates of Opportunistic Infections Associated with PI-based Therapy

Palella, F.J. et al. N. Engl. J. Med. 338(13):853-860, March 26, 1998.

0

5

10

15

20

1994 1995 1996 1997

Year

Number of

opportunistic

infections

per 100

person-years

M. avium complexCytomegalovirusP. carinii pneumonia

BrainToxoplasmosis (Toxo)Crytpococcal meningitis

Gut

Eyes

Mouth & Throat

Genitals

Lungs

Skin

Cytomegalovirus (CMV)Cryptosporidiosis

Mycobacterium avium complex (MAC)

Pneumocystic jirovecii pneumonia (PCP)Tuberculosis (TB)

Histoplasmosis

Cytomegalovirus (CMV)

Herpes simplexShingles

Genital HerpesHuman papillomavirus

Vaginal Candidiasis

Candidiasis (yeast)

Opportunistic Infections common in Patients with HIV and AIDS

PAETC HIV/AIDS Basic Training Curriculum Guide June 2007.

Coughing, shortness of breath Seizure; lack of coordination Mental symptoms such as

confusion and forgetfulness Fever Vision loss Nausea, abdominal cramps,

vomiting; severe and persistent diarrhea

Weight loss; extreme fatigue Severe headache

Antibiotics Antifungal agents Chemotherapy Radiation Steroids Inhalation Therapy Intravenous Therapy

Some Signs & Symptoms Prophylaxis & Treatment

Opportunistic Infections (2)

PAETC HIV/AIDS Basic Training Curriculum Guide June 2007.

You are a clinician at an Urgent Visit Center. Your patient is Joe. Joe is a 20yo African American maleComplains of flu-like symptoms:• Headache• Fever• Cough• Nausea & vomiting• Malaise• Weight loss• Vague myalgias• Rash• Diarrhea

Case Study

Patient Reports:

• In college, but has been home for the summer.

• Lives with his parents and younger brother. Brother has had a cold for the past week.

• Considers himself to be healthy. Denies taking any prescription medications

More About Joe

• Febrile 101.3• Erythematous macropapular rash on face and

trunk, involving palms & soles• Cervical and inguinal LAD• + Pharyngitis• Rest of exam is WNL

Physical Exam Reveals

Given what you know about Joe – Would you offer an HIV test as part of today’s encounter?

1 2

0%0%

1. Yes

2. No

Which of the following questions would you want to ask Joe?

1 2 3 4

0% 0%0%0%

1. If he has ever used IV drugs

2. If he uses condoms

3. How many sex partners he has had in the past 3 years

4. All of the Above

Based on the 2006 CDC Recommendations, Would you offer Joe an HIV test today?

1 2

0%0%

1. Yes

2. No

You decide to screen Joe for HIV – The lab notifies you that his EIA is reactive and the sample has been sent for a Western Blot. The first thing you should do is?

1 2 3 4

0% 0%0%0%

1. Bring Joe into the office for an urgent appointment to inform him that he has HIV

2. Order baseline labs

3. 1 and 2

4. None of the above

Two days later – You get the results on the Western Blot. Your suspicions are confirmed.

Joe has HIV

CD4 = 150 cells/mm3

Viral load assay = 150,000 copies/mL

Joe’s appointment with the Infectious Disease specialist is one month away.

Joe’s CD4 and Viral Load labs are back

Based on Joe’s labs, is he at risk for opportunistic infections?

1 2

0%0%

1. Yes

2. No

1. HIV/AIDS is found in every county in the state of Indiana, but is particularly concentrated in Marion and surrounding counties, as well as Lake, Porter and St. Joseph counties.

2. HIV is a virus that weakens a person’s immune system . AIDS is a diagnosis, based off of a collection of symptoms, used to determine HIV disease progression.

Summary

3. HIV is transmitted through blood, semen, vaginal secretions and breast milk.

4. After the infection and acute HIV stages, a person could live for many years without any signs or symptoms of illness.

Summary

5. EIA/ELISA Tests are used to identify HIV antibodies in a person’s body. A Western Blot must be used to confirm a person’s HIV status before a diagnosis is given.

6. If a person is screened for HIV with an HIV antibody test during the window period, a false negative could result.

7. MATEC is here as a resource for you!!

Summary

AETC National Resource Centerhttp://www.aids-etc.org/

AIDSinfoDHHS Treatment Guidelineshttp://aidsinfo.nih.gov/

Centers for Disease Control & Prevention (CDC)http://www.cdc.gov/hiv/default.htm

HIV InSitehttp://hivinsite.ucsf.edu/InSite

National HIV/AIDS Clinicians’ Consultation CenterWarmline, PEPline, Perinatal HIV Hotlinehttp://www.hivcntr.ucsf.edu

MATEChttp://www.matec.info

Resources