31st Annual Winter Update
Indiana Osteopathic Association
December 7, 2012
Indianapolis, IN
cgenske@ecommunity.com
Outline
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History
Epidemiology
Transmission
Natural History
Testing Recommendations
Diagnosis
Clinical Manifestations
Treatment
Health Maintenance
Hot Topics
 Pre-exposure prophylaxis (PrEP)
 Post-exposure prophylaxis (PEP)
June 5, 1981:
MMWR published 5 cases of PCP
in homosexual men from California

July 3, 1981: 26 additional cases

Dec 10, 1981: 3 NEJM papers
describe cases
July
1981
41 cases Kaposi’s Sarcoma (KS)
1982
GRID = Gay-related Immune Deficiency
June
1982
July
1982
20 states with disease
Dec
1982
Hemophiliacs died
1983
1292 of 3064 people died
April
1984
James Mason isolated LAV
Robert Gallo isolated HTLV-III
AIDS = Acquired ImmunoDeficiency Syndrome
1985
March
1985
First test to identify HIV antibodies developed
1985
Rock Hudson died of AIDS
1986
50% of hemophiliacs infected
1986
Surgeon General’s first report
on AIDS
1986
Drug trials begin (ACTG)
March
1987
FDA approved first drug (AZT)
1988
45,000/83,000 patients had died
April
1990
Ryan White died
1991
FDA approved second drug (ddI)
1990
Ryan White CARE Act passed
1994
AZT reduces MTCT
1994
2 drugs are better than 1
1995
First HIV viral load testing
1996
HAART in use (3+ drugs)
2006
First one pill once daily regimen approved
2009
DHHS guidelines recommend initiation of ART for CD4
<500
2010+
New hope for HIV prevention (PrEP)
AIDS Mortality Rates: 19952001
Mortality vs. ART utilization
Deaths per 100 person-years
35
USE OF ART
30
25
DEATHS
20
50
15
10
25
5
0
1995
8
75
1996
1997
1998
1999
2000
Percentage of patient-days on ART
100
40
0
2001
Courtesy: AETC
Adult HIV Prevalence, 2010
Courtesy: UNAIDS
Courtesy: UNAIDS
Courtesy: UNAIDS
Changes in HIV Incidence, 2001-2010
Epidemiology – Worldwide

34 million living with HIV / AIDS
 ~2/3 in Sub-Saharan Africa, mostly heterosexual
 60% unaware of being infected
 7,000 new infections each day (2.5 million/yr)
○ 900 of these are children < 15 yo
○ 47% in women
○ 39% in young people (15-24)
○ African Americans 8x rate of HIV cases compared
to whites
 1.7 million died in 2011

Only 25% are receiving treatment !!
www.unaids.org
Epidemiology – U.S.

1,180,000 HIV+ (1 in 200)
 20% undiagnosed
 488,000 living w/ AIDS
 21,000 die each yr

50,000 newly infected each yr
 61% MSM
 1 of every 5 homosexual urban males HIV+
 1 of every 22 African Americans will be
infected

Incidence in Washington D.C. is 3%!
Epidemiology – U.S.
Only 1 of 5 have undetectable virus ->
(close to) non-contagious.
 Over 800,000 have detectable virus ->
CONTAGIOUS!
 Individuals unaware of their HIV+,
particularly those recently infected, are
major contributors to the ongoing
epidemic

Epidemiology – Indiana

Persons living with HIV/AIDS in Indiana
as of June, 30, 2012
 Total = 10,420
○ 80% Male (8,388)
○ 20% Female (2,032)
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Race/Ethnicity of HIV patients
 53% White (5,541)
 36% Black (3,764)
 7% Hispanic (780)
0.1% infected
0.6% infected
0.2% infected
Spotlight on HIV/STD/Viral Hepatitis, Indiana Semi-Annual Report, June 2012:
http://www.in.gov/isdh/files/At_A_Glance-Dec.pdf
Indiana IN Depth Profile. http://www.stats.indiana.edu/c2010/dp1/FactfinderINandUS.pdf
HIV Transmission/Acquisition

Found in blood, semen, or vaginal fluid of an
infected person

HIV is transmitted/acquired by:
 Having sex (anal, vaginal, or oral) with someone
infected with HIV
 Sharing needles, syringes with someone who has
HIV
 Exposure (in the case of infants) to HIV before or
during birth, or through breast feeding
Probability of HIV Transmission
INFECTION ROUTE
Sexual Intercourse
Male-to-male transmission
Male-to-female transmission
Female-to-male transmission
RISK OF INFECTION
1 in 10 - 1 in 1,600
1 in 200 - 1 in 2,000
1 in 700 - 1 in 3,000
Transmission from mother to infant
Without AZT
With AZT
With HAART
1 in 4
Less than 1 in 10
1-2 in 100
Other
Transfusion of infected blood
Needle stick
Needle sharing
95 in 100
1 in 250
1 in 150
Royce, et al
Natural History
Acute Infection (days to weeks)
 Partial Control of HIV (weeks to months)
 Asymptomatic HIV Infection (1-10+
years)
 Symptomatic HIV Infection & AIDS
(years)
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Natural History of HIV Infection
Primary
infection
CD4 T Cells/mm3
Death
Possible acute HIV syndrome
Wide dissemination of virus
Seeding of lymphoid organs
1100
1000
Opportunistic
diseases
900
10E7
Clinical latency
800
10E6
700
Constitutional
symptoms
600
10E5
500
400
10E4
300
200
10E3
100
0
0
3
6
9
Weeks
12
1
2
3
4
5
6
7
Years
8
9
10
11
Viremia (copies/mL plasma)
1200
CD4 Lymphocyte Count
Reflects immune status
 Normal CD4 count: 500 - 1,500 cells/mm3
 CD4 count decreases as HIV disease
progresses
 CD4 counts differ daily
 Overall trend of CD4 counts over time
most important
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CD4 < 200 = AIDS (or opportunistic infection)
HIV Viral Load
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Number of HIV RNA copies per mL of blood
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“High” viral load: 5,000 to >1,000,000 copies
 High reproduction rate
 Disease will progress faster
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“Low” viral load: 200 to 500 copies
 Low reproduction rate
 Risk of disease progression is low
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“Undetectable” viral loads: <50 or <400
 Below the threshold needed for detection
2006 CDC HIV Testing Recommendations
CDC Testing Guidelines, 2006

Offer routine testing in all health care
settings to:
 13- to 64-year-olds
 Anyone with Tuberculosis (TB)
 All patient seeking treatment for STDs
 All pregnant females
 Any health care worker exposed to blood or
body fluids
 Anyone who requests testing
CDC Testing Guidelines, 2006

Who should be tested at least annually?
 IVDA and their sex partners
 Persons who exchange sex for money or
drugs
 Sex partners of HIV-infected persons
 Persons with multiple sex partners
Why emphasize early diagnosis?
Individuals unaware of their HIV+,
particularly those recently infected, are
major contributors to the ongoing epidemic
 Earlier treatment:

 Lowers mortality
○ “Delayed Therapy” group (<500) had 94% higher mortality!*
 Decreases risk of transmission by 96%**
 May improve immune system by (partially) restoring CD4
count more towards normal
 May lower long-term complications associated w/
inflammation (though biomarkers of inflammation may
never return to normal )
*Kitahata et al **Cohen et al
Diagnosis

Screening: ELISA antibody (or other rapid
tests)
 Now recommended to be part of routine medical care
(yearly if high risk)
 Time to + : ~ 3 wks
 Newer assays may detect infection as early as 10 - 14
days; still, very early infection will not be detectable
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Confirmation: Western Blot
 Time to + : ~4-5 weeks
 Any two: p24, gp41, gp120/160 -> positive
 One + band, or other + bands -> “indeterminate”
○ Either wait and repeat, or obtain quantitative assay for HIV by
PCR = “viral load”
Some causes of FalseNegative HIV Antibody Tests
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Acute HIV Infection
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Advanced HIV Infection

Antiretroviral Therapy
Some causes of FalsePositive HIV Antibody Tests
Liver Disease
 Autoimmune Disorders
 CKD/ESRD
 Congenital bleeding disorders
 Recent Infection with dengue, malaria,
hepatitis B, leprosy
 Immunizations

Diagnosing Acute HIV: Window Period
Window Period = Time between infection and detectable HIV antibodies
Courtesy: AETC
Diagnosing Acute HIV: Acute HIV
Acute HIV
Acute HIV = patients may present with acute retroviral syndrome/illness
Laboratory Diagnosis of Acute HIV
Acute HIV
• Positive HIV-1 RNA Assay
• Negative HIV Antibody Test
Course of HIV Infection
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Chronic and progressive infection
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Acute Retroviral Syndrome (Acute Infection)
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Flu-like symptoms
Period of active viral replication
HIV Ab levels may be below the limit of detection
(negative ELISA), however the patient is HIGHLY
CONTAGIOUS!
Acute Retroviral Syndrome

80 - 90% with acute HIV infection report symptoms
consistent with acute retroviral syndrome
 “Mononucleosis-like” syndrome
 Onset of symptoms typically 2-4w after exposure
 Median duration of symptoms is 2 weeks
 Fever (96%), adenopathy (74%), pharyngitis (70%), rash
(70%), myalgia (59%), night sweats (50%),
thrombocytopenia (45%), leukopenia (45%), diarrhea,
headache
 May also present as “aseptic/viral meningitis”
Acute Retroviral Syndrome
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Most acutely infected patients seek
medical attention
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This syndrome may be missed in up to
75% of presenting patients
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HIV antibody levels usually negative
 Check HIV RNA PCR
Course of HIV Infection
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Asymptomatic Phase (6 months - >10 years)
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Host immune response controls viral replication
CD4 cell count gradually declines
Symptomatic Phase
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Host immune response begins to wane
CD4 cell count < 500 cells
○
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Bacterial pneumonia, thrush, vaginal candidiasis, shingles,
oral leukoplakia
CD4 cell count < 200 cells
○
Opportunistic infections

Pneumocystis jirovecii pneumonia, CMV retinitis, Candida
esophagitis, Toxoplasma encephalitis, Histoplasmosis,
Cryptococcal meningitis, MAC, lymphoma, etc
CD4 Count & Risk of Clinical
Disease
Clinical Findings in HIV Infection
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General
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Generalized LAD
Thrombocytopenia (ITP)
Elevated total protein
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Dermatologic
Seborrheic dermatitis
Zoster (shingles)
Superficial fungal infections
Warts
Eosinophilic folliculitis
Mucocutaneous
Oropharyngeal candidiasis
Oral or genital herpes
Gingivitis/peridontitis
Oral Hairy Leukoplakia
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Respiratory
Recurrent sinusitis
Community acquired
pneumonia
Tuberculosis
Images courtesy of: AIDS Images Library www.aidsimages.ch
Images courtesy of: AIDS Images Library www.aidsimages.ch
Other clues to possible HIV
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Unusual presentation of a common illness
 Pneumococcal pneumonia w/ bacteremia in a
young person
 Salmonella, shigella, campylobacter bacteremia
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Presentation of an unusual illness
 More advanced/severe dx than expected
 Unusual age for illness
TB, especially w/ unusual presentation
 Other STDs
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Other clues to possible HIV
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Common complaints
 Persistent fatigue, recurrent fevers,
chills/night sweats, persistent diarrhea,
weight loss
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Routine lab abnormalities
 Leukopenia (low WBC)
 Lymphopenia (low lymphocytes)
 Thrombocytopenia (low platelets)
 Mild transaminitis
 Elevated protein
Goals of HIV Therapy
Maximal and durable suppression of viral load
– reduces the risk of disease progression
 Restoration and/or preservation of
immunologic function
 Improvement in quality of life
 Reduction in HIV-related morbidity and
mortality
 Prevent vertical transmission of HIV
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HOPS: Mortality and Frequency
of HAART Use
35
100
Deaths
30
80
25
60
20
15
40
10
20
5
0
Use of HAART
0
1994
1995
1996
1997
Palella. N Engl J Med 1998;338:853. Update: Palella. Personal Communication, 1999.
1998
1999
HAART, % patient-days
Deaths per 100 person-years
Over 90% of HAART Regimens PI Based
When to Treat?*
Symptomatic, or “AIDS-defining” illness
 CD4 at 500 or less
 Pregnancy
 HIV-associated nephropathy (to preserve kidney
function)
 Active hepatitis B co-infection (10% of U.S. HIV+)
 HIV RNA > 100,000 copies/mL
 High risk for secondary transmission
 Age > 50
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*March 27, 2012 - NIH Guidelines for the use of Antiretroviral Agents in HIV-1 Infected
Adults and Adolescents
When to Treat?*
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When circumstances permit, offer to ALL
individuals, regardless of CD4 count
*Thompson et al.
Predictors of Inadequate Adherence
Regimen complexity & pill burden
 Poor clinician-patient relationship
 Active drug use or alcoholism
 Unstable housing
 Mental illness
 Lack of patient education
 Medication adverse effects
 Fear of medication adverse effects
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Current Treatment Options
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31 drugs currently
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6 classes
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Now 3 options for 1 pill once daily
 Atripla ®
 Complera ®
 Stribild ®
Treatment
Common drug interactions with HAART to
consider:
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Benzodiazepines
Antidepressants
Anticonvulsants
Rifampin
OCPs
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Statins
Erectile dysfunction
agents
Antifungals
Acid reducers
Nasal steroids
Health Maintenance
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Immunizations
 Influenza Annually (IM route)
 Pneumovax (entry into care and 5 years
later)
 Hepatitis A vaccine series
 Hepatitis B vaccine series
 Tdap/Td
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Annual PPD/quantiferon
CDC. 2011 ACIP Guidelines
Health Maintenance
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Immunizations to AVOID:
 Live vaccines to avoid:
○ Intranasal Influenza vaccine
○ Smallpox
○ OPV (no longer available in U.S.)
○ BCG
 May be ok if CD4 >200 and pt asymptomatic:
○ MMR
○ Varicella
○ Zoster
CDC. 2011 ACIP Guidelines
Health Maintenance
Patients trust their primary care providers. Your support of is
critical in keeping HIV patients healthy.
You can:
• Manage co-morbid conditions (Diabetes, Cardiovascular Health)
• Provide routine preventative care – (PAPs, Immunizations,
Colonoscopy, etc..)
• Encourage routine dental and vision care
• Provide support messages about reducing tobacco use, EtOH use
and/or other drug use
• Drive home the importance of proper diet, exercise and rest
• Promote “Safer Sex” prevention practices
• Support adherence (meds and follow-up with ID)
• Provide emotional support, recommend counseling if needed
• Referral to local AIDS service organizations: Damien Center,
Concord Center, Step-Up, etc
You are the Experts!
Pre-Exposure Prophylaxis (PrEP)

In PrEP, an HIV uninfected individual
takes antiretroviral medication (oral or
topical) ahead of ongoing HIV
exposures. By having these medications
in the bloodstream/tissues, HIV may be
unable to establish infection.
Pre-Exposure Prophylaxis (PrEP)

Select, high-risk circumstances
 Once daily Truvada ®




(FTC/TDF)
75+% effective among those w/
detectable drug levels
Controversial
Expensive
See Truvada.com
○ Includes a 17-point check list,
agreement form, training guide,
etc
Pre-Exposure Prophylaxis (PrEP)

Vaginal gel (Tenofovir)
 Initial study (CAPRISA 004) showed it to be

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

>50% effective when used regularly*
Also showed decreased genital herpes
transmission
Less effective in other studies
More studies ongoing
Not yet ready for “Prime Time”
*Karim et al.
Post-Exposure Prophylaxis (PEP)

Needle stick
 Determine status of both source and patient
at baseline if possible for:
○ HIV, HBV, HCV, RPR
 If source is HIV positive, ideally treatment
should be started within 2 hours (72 hours
max)
○ Treatment continued for 28 days
○ Choice of regimen complex, based on many
factors (typically 3 drugs)
○ Post Exposure Prophylaxis (PEP) hotline:
 1-888-448-4911 (24 hours a day)
Post-Exposure Prophylaxis (PEP)

Needle stick (cont’d)
 Risk of transmission is 1 in 300 (0.3%)
○ Highly correlated with viral load
 Close monitoring of patient while on PEP
○ Weekly visits
 Rechecking labs up until 6-12 months post
exposure
○ 6 weeks, 3 months, 6 months, 12 months
Post-Exposure Prophylaxis (PEP)

Sexual encounter
 May be unable to determine source patient
status
 Risk of transmission dependent on sexual
act (0.01-0.5%)
 If felt to be a high risk situation, may decide
to start PEP
○ Check baseline status on patient
○ Start PEP within 72 hours (3 drug regimen)
○ Monitor closely (weekly appts)
 Continued f/u for 6-12 months after exposure
Summary
20-25% of HIV infected individuals do
not know they are infected
 Test often, treat early
 Effective treatment can:

 Reduce risk of transmission to near zero!
 Better long term survival

HIV is evolving into a chronic disease,
PCPs play a prominent role in overall
health
References
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http://www.aidsetc.org
http://www.aidsinfo.nih.gov
http://www.unaids.org
Spotlight on HIV/STD/Viral Hepatitis, Indiana Semi-Annual Report, June 2012:
http://www.in.gov/isdh/files/At_A_Glance-Dec.pdf
Indiana IN Depth Profile. http://www.stats.indiana.edu/c2010/dp1/FactfinderINandUS.pdf
Royce, et al. NEJM 336:1072-1078, 1997
CDC. Revised guidelines for HIV counseling, testing, and referral. MMWR 2006;55[No. RR14]:1-17
CDC. General Recommendations on Immunization. Recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR January 28, 2011;60 (RR02); 1-60
Thompson et al. Antiretroviral Treatment of Adult HIV Infection. JAMA 2012;308: 387-402
Kitahata M et al, NEJM 2009; 360:1815-26
Cohen et al. Medical Progress: Acute HIV Infection. NEJM 2011;364:1943-54
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of
antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and
Human Services. March 27, 2012. Available at
http://aidsinfo.nih.gov/Guidelines/HTML/1/adult-and-adolescent-arv-guidelines/0
Interim Guidance for Clinicians Considering the Use of Preexposure Prophylaxis for the
Prevention of HIV Infection in Heterosexually Active Adults. MMWR. August 10, 2012 /
61(31);586-589
Q Abdool Karim et al. Science 2010;329:1168-1174
Grant R et al, N Engl J Med 2010;363:2587-99