To Get your CMEs

1
To Get your CMEs

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  to our website, www.stdptc.uc.edu
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• Follow directions to register
• Complete the evaluation
• Print out your CEU certificate!

2
HIV Primer for the Non-ID Clinician

• Jan M. Stockton, RN, MSN, AACRN
• University of Cincinnati
• AIDS Clinical Trials Unit
• stocktjm_at_uc.edu

3
Questions?

• You may type your question here during the live
  presentation or call our
• Consultation Phone Line
• 1-800-459-2820
• Or Fax us at
• 513-357-7306

4
HIV Primer for the non-ID Clinician

• Epidemic in US
• Laboratory Testing in HIV disease
• Viral Replication Cycle
• Antiretroviral Therapy
• Common Complications
• When to Offer HIV Testing
• Resources

5
Key Snapshot of US Epidemic

• Number of new HIV infections in 2006
• 56,300
• Number of people living with HIV disease
• 1.2 million including 440,000 with AIDS
• Number of AIDS deaths since beginning of epidemic
• 565,927 including 14,627 in 2006
• Percent of people infected with HIV but dont
  know it 25

6
Laboratory Testing Diagnostic

• ELISA/EIA screening
• Western Blot confirmation
• Rapid Testing
• OraSure oral secretions
• OraQuick finger stick
• Window Period
• Up to three months after onset of infection
• p24 antigen or HIV viral load testing

7
Laboratory Testing Clinical Monitoring

• Serum markers
• CD4 count (normal 500-1500)
• Lymphocyte Sub-sets (LSS)
• Viral Load
• HIV quant. (400-750,000)
• HIV ultraquant. (50-10,000)

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HIV infection is characterized by a steady
decline in the number of CD4 cells
Acute Infection
Asymptomatic HIV Infection
AIDS
CD4 Cell Count
1,000
CD4 Cells
500
200
4-8 Weeks
Up to 12 Years
2-3 Years
Time
10
HIV infection is characterized by a steady
decline in the number of CD4 cells
Acute Infection
Asymptomatic HIV Infection
AIDS
CD4 Cell Count
1,000
CD4 Cells
500
200
high risk of opportunistic infections
4-8 Weeks
Up to 12 Years
2-3 Years
Time
11
CD4 Count, Viral Load, Clinical Course
Primary Infection
Sero-conversion
Intermediate Stage
AIDS
CD4 Cell Count
Viral Load
1,000
CD4 Cells
500
4-8 Weeks
Up to 12 Years
2-3 Years
12
Laboratory TestingTreatment Planning

• Resistance Testing
• Recommended for all treatment-naïve patients
  entering into clinical care.
• May be repeated when treatment is to begin
• Will be repeated for treatment failures
• Genotyping
• Documents mutations present in dominant strain
• Phenotyping
• Demonstrates level of response to antiretroviral
  agents

13
Laboratory TestingTreatment Planning

• Tropism assay
• Performed prior to initiation of CCR5 antagonist
• Identifies R5, X4, D/M (dual/mixed)
• HLA-B5701
• Performed prior to starting abacavir therapy to
  reduce risk of hypersensitivity reaction
• HLA-B5701 positive patients should not be
  prescribed abacavir and notation recorded as
  abacavir allergy in medical record.

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Viral Replication Cycle
Attachment and Fusion
Reverse Transcription
Translation
Transcription
Assembly and Maturation
Integration
AIDSmeds.com
15
Antiretroviral Therapy

• Co-Receptor Antagonists
• Maraviroc (Selzentry?)
• Dose adjusted with other ARVs
• Caution with pre-existing liver disease
• Vicriviroc (investigational)
• Approved for use with CCR5 CD4 cells
• Attachment Inhibitors
• Enfuvirtide (Fuzeon?, T-20)
• Subcutaneous injection q12h
• Requires reconstitution
• May result in local skin reaction

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Antiretroviral Therapy

• Nucleoside/Nucleotide Reverse Transcriptase
  Inhibitors
• Zidovudine (Retrovir?, AZT)
• Stavudine (Zerit?, d4t)
• Didanosine (Videx? /Videx EC?, ddI)
• Zalcitabine (Hivid?, ddC)
• Lamivudine (Epivir?, 3TC)
• Abacavir (Ziagen?, ABC)
• Emtricitabine (Emtriva?, FTC)
• Tenofovir (Viread?, TDF)

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Fixed Dose Combinations

• Combivir? (AZT 3TC)
• Trizivir? (AZT 3TC ABC)
• Epzicom? (3TC ABC)
• Truvada? (TDF FTC)
• Atripla? (TDF FTC EFZ)

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Antiretroviral Therapy

• Non-Nucleoside Reverse Transcriptase Inhibitors
• Nevirapine (Viramune?)
• Efavirenz (Sustiva?)
• Etravirine (Intelence?)

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Antiretroviral Therapy

• Integrase Inhibitor
• Raltegravir (Isentress?)
• Elvitegravir (Investigational)

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Antiretroviral Therapy

• Protease Inhibitors
• Saquinavir (Invirase?, SQV)
• Indinavir (Crixivan?, IDV)
• Nelfinavir (Viracept?, NLF)
• Lopinavir/Ritonavir (Kaletra?, LPV/r)
• Atazanavir (Reyataz?, ATZ)
• Fosamprenavir (Lexiva?)
• Ritonavir (Norvir?, RTV)
• Tipranavir (Aptivus?, TPV)
• Darunavir (Prezista?, TMC 114)

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Mortality and HAART Use Over Time HIV Outpatient
Study, CDC, 1994-2003
14
0.9
0.8
12
0.7
10
0.6
Patients on HAART
8
0.5
Patients on HAART
Deaths per 100 PY
Deaths per 100 PY
0.4
6
0.3
4
0.2
2
0.1
0
0
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
Year
Highly Active Anti-Retroviral Therapy
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When to start treatment?

• AIDS
• CD4lt 350/mm3
• CD4gt 350/mm3
• Pregnancy
• HIV-associated nephropathy
• Hepatitis B treatment
• Optional VLgt100K cells/ml, serodiscordant
  couples, acute HIV infection

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Why wait to start treatment?

• 95 adherence required to minimize risk of
  developing resistance mutations.
• Challenges to adherence
• Pill burden
• Dosing intervals
• Food restrictions
• Storage needs (i.e., refrigeration)
• Tolerability issues (i.e., bad taste, GI upset)
• Short and long term side effects (i.e.,
  peripheral neuropathy)
• 15 of newly diagnosed patients in 2003 and 2004
  had one or more resistance mutations.

24
ARV Treatment Issues in Inpatient
Settings

• Antiretroviral medication errors among
  hospitalized patients with HIV infection
• Retrospective audit of medical record and
  computerized provider order entry system
• 77 admissions total
• Errors in the prescribing of antiretroviral
  medications for approximately one-quarter of
  these admissions, despite the use of a
  computerized order entry system.

Rastegar DA et al. Clinical Infectious Diseases
43(7) 2006
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ARV Treatment Issues in Inpatient
Settings

• Errors found
• Failure to appropriately adjust doses for renal
  insufficiency
• Combining ARV with contraindicated medication
• Administered only 1 or 2 ARVs
• Unexplained delay in continuing HAART
• Review not designed to capture
• Patients who should have been on ARV and werent
• Patients receiving more than 3 ARVs before
  admission but given 3 or less while hospitalized.

Rastegar DA et al. Clinical Infectious Diseases
43(7) 2006
26
Special PresentationsAcute HIV Infection

• Primary HIV infection
• Interval from initial infection to time that HIV
  antibody detectable
• Viral load very high
• Reported in 50-75 of cases
• Symptoms usually occur within 2-4 weeks of
  infection
• Greater symptoms associated with higher V.L.,
  faster progression to AIDS

• Fever, night sweats
• Headache
• Fatigue
• Enlarged nodes

• Pharyngitis
• Myalgia/arthralgia
• Anorexia
• Rash/urticaria

CF Kelley et al. J Acquir Immune Defic Syndr
2007 45(4)445-448
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Special Presentations Immune Reconstitution
Syndrome

• Development of inflammatory disease in response
  to specific opportunistic pathogens within a few
  weeks or months of starting ARV, resulting in
  rapid and marked rise in CD4 count from very low
  pre-treatment levels
• Caused by enhanced immune response to
  disease-specific antigens, leading to
  overproduction of inflammatory mediators

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Special Presentations Immune Reconstitution
Syndrome

• Presents as exacerbation of partially or
  successfully treated or previously undiagnosed
  (subclinical) OI
• TB, MAC, CMV, cryptococcus, PCP, toxoplasma, VZV,
  hepatitis
• Must be distinguished from other causes of
  disease
• Clinical findings
• Initiation of ART
• Increase in CD4 count
• Treatment
• Continue ART if possible
• Treat OI as indicated
• Add anti-inflammatory agents as needed

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Common Complications

• OIs and prophylaxis
• PCP, MAC
• Candida oral, esophageal
• HSV, VZV
• Diarrhea
• Metabolic complications
• Insulin resistance/diabetes
• Lipid abnormalities
• CNS complications
• Co-infections
• TB, Hepatitis B C, STDs

30
Pneumocystis Pneumonia PCP

• Pneumocystis jiroveci
• Less common since use of prophylaxis
• Bactrim or Dapsone for CD4 lt 200
• Presenting symptoms
• Dyspnea with mild exertion
• Fever, night sweats
• Nonproductive cough
• Weight loss
• Fatigue

31
Pneumocystis Pneumonia

• Pulse oxymetry
• Sharp ? in O2 sat with exertion
• Chest examination
• Minimal rales
• Cough with deep inspiration
• May be unremarkable
• CXR bilateral interstitial infiltrates
• Rule out other pulmonary diseases

32
Pneumocystis Pneumonia

• Treatment
• TMP-SMX DS 2 tablets 3x/day 21 days
• Corticosteroids may be added.
• Alternatives for sulfa allergy
• Pentamidine
• Dapsone/trimethaprim
• Atovaquone
• Trimetrexate/leukovorin
• Continue secondary prophylaxis until CD4 gt 200
  for 6 consecutive months

33
M. Avium Complex (MAC)

• Organisms commonly found throughout the
  environment
• Enter via respiratory, GI tract
• Disseminated infection typically occurs when CD4
  lt 50
• 40 when no MAC prophylaxis given
• May present as immune reconstitution syndrome

34
M. Avium Complex (MAC)

• Prophylaxis
• Azithromycin 1200 mg. oral qwk
• Clarithromycin 500 mg. oral BID
• Treatment
• Ethambutal 15 mg/kg oral once daily
• PLUS EITHER
• Clarithromycin 500 mg oral BID
• OR
• Azithromycin 500-600 mg oral once daily

35
Oral Hairy Leukoplakia
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Oral/Esophageal Candidiasis

• Most common intraoral lesion in HIV
• Angular chelitits
• Erythematous
• Pseudomembranous
• Esophageal involvement
• Difficult/painful swallowing
• Food gets stuck

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Oral Candida Infection Angular chelitis
38
Oral Candida Infection Erythematous
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Oral Candidiasis Pseudomembranous
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Oral/Esophageal Candidiasis

• Treatment
• Fluconazole 100 mg. daily 7-14 days
• Clotrimazole troches 5x/day 14 days
• Nystatin swish/swallow 5 ml 4x/day 14 days
• Itraconazole 200 mg. daily 7-14 days
• May require IV antifungal agents

41
Aphthous Ulcers

• Painful ulcers with depressed centers
• Treatment Corticosteroids
• Topical
• Dexamethasone elixir 0.5 mg/5 ml swish and spit
• Magic mouthwash
• Severe ulceration prednisone 40-60 mg. daily x
  7 days with taper.

42
Aphthous Ulcers
43
Varicella Zoster

• 10x increase with HIV infection
• Assessment findings Ive got a rash.
• Blisters
• Linear
• Unilateral
• Burning, painful

44
Varicella Zoster (Shingles)
45
Varicella Zoster (Shingles)
46
Varicella Zoster (Shingles)

• Treatment
• Famciclovir 500 mg. 3x/day 7-10 days
• Valacyclovir 1 gm q8h 7 days
• IV acyclovir 10-12 mg/kg q8h 7-14 days
• Dissemination has occurred
• Lesions not responding to oral therapy
• Pain is intractable
• Should begin within 72 hours of outbreak
• Reduce dosage with renal impairment
• Pain management
• Acute phase
• Post-herpetic neuralgia

47
Diarrhea

• Assessment
• Onset, frequency, consistency, color
• Presence of blood
• Nausea, vomiting, abdominal pain
• Use of antidiarrheal agents
• Exposure to unsafely prepared food, contaminated
  water, pets, farm animals
• Recent travel
• Medications HIV, other antibiotics,
  recreational

48
Diarrhea

• Disease-related
• Opportunistic infection
• HIV enteropathy
• Cultures Routine, OP, C. diff. toxin,
  Cryptosporidium, Giardia
• Colonoscopy with biopsy and cultures for HIV, CMV
• Treatment-related
• Protease inhibitors
• Manage with anti-diarrheal agents

49
Neurologic Complications

• HIV is a neurotropic virus
• Acts directly on nerve tissue
• HIV crosses the blood-brain barrier
• Invades CNS early in course of infection
• HIV impacts all levels of CNS
• Brain, spinal cord, nerves and meninges
• HIV has indirect affect on neurons
• Stimulates secretion of neurotoxins and
  inflammatory cytokines (TNFa, IL-1)

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CNS Complications

• B Cell lymphoma
• Cryptococcal meningitis
• Delirium
• HIV-associated dementia
• HIV encephalopathy
• HSV encephalitis
• Progressive multifocal leukoencephalopathy (PML)
• Tertiary syphilis
• Toxoplasmosis

51
Neuropsychiatric Complications

• Minor Cognitive-Motor Disorder (MCMD)
• Mild cognitive or motor impairment
• Symptoms do not interfere with ADLs
• HIV-Associated Dementia
• Severe cognitive, motor, behavioral changes
• Significant impairment in ADLs
• HIV-Associated Delirium
• Fluctuating levels of consciousness,
  hallucinations
• Cognitive deficits
• Unpredictable shifts in emotion

52
Neurologic/Neuropsychiatric Work-Up

• Initial Labs
• CD4 count to assess risk for OI
• Toxoplasma, cryptococcal antibodies
• Electrolyte, glucose levels
• Neuropathy, dementia vitamin B12, TSH
• Cranial nerve abnormalities RPR
• CNS symptoms CT, MRI
• Fever LP after imaging to rule out CNS mass
• Suspected drug/ETOH abuse toxicology screen
• New onset seizure EEG
• Refer to neurologist, psychiatrist for additional
  testing

53
Co-Infections M. Tuberculosis

• Most common severe OI associated with HIV
  pandemic.
• HIV and TB cause more deaths than any other
  infectious diseases worldwide.
• Biologic synergy
• HIV-induced immunosuppression increases
  susceptibility to TB infection
• Active TB infection enhances HIV replication
  through immunologic stimulation

54
M. Tuberculosis Treatment

• Latent TB Isonizid 300 mg daily 6-12 months
• HIV 9-12 months or longer
• DOT 15 mg/kg 2x/week
• Active TB 2-4 agents for 6-9 months
• Isoniazid (INH)
• Rifampin (RIF)
• Ethambutal (EMB) or Streptomycin (SM)
• Pyrazinamide (PZA)
• Rifapentine
• Rifabutin (RFB)

55
M. Tuberculosis Treatment

• Special considerations in HIV
• TB may be more severe
• Directly observed therapy (DOT) is strongly
  recommended
• Acquired drug resistance may occur
• Potent ART may be complicated by overlapping drug
  toxicities, drug-drug interactions, immune
  reconstitution inflammatory reactions.

56
Co-Infections Hepatitis B

• Transmitted via blood exposure, sexual contact,
  perinatal transmission
• Up to 90 HIV patients currently or previously
  infected with HBV
• Most clear infection without treatment.
• 10 develop chronic HBV infection, with hepatic
  fibrosis, cirrhosis, ESLD, hepatocellular
  carcinoma
• HIV infection appears to increase risk of chronic
  HBV infection after HBV exposure.
• HIV/HBV coinfection may result in faster
  progression of liver disease.

57
Co-Infections Hepatitis C

• Transmitted primarily through blood exposure,
  although perinatal and sexual transmission has
  also been reported
• Up to 90 HIV-infected IDUs and 15 HIV-infected
  MSM are co-infected with HCV
• 60-85 of people infected with HCV become
  chronically infected.
• Complications include hepatic fibrosis,
  cirrhosis, ESLD, HCC

58
Co-Infections STDs

• HIV more common in persons with STD
• STDs more common in person with HIV
• Most frequently seen in HIV care
• Syphilis
• Gonorrhea
• Chlamydia
• Herpes
• HPV
• Vaginal candidiasis
• Sex partners need follow up and treatment.

59
When to Recommend HIV Testing

• 39 of all HIV infections diagnosed in 2003
  progressed to AIDS within 12 months.
• Not started on treatment soon enough.
• Not diagnosed soon enough.

60
HIV Testing Red Flags

• Pregnancy
• Active tuberculosis
• Symptoms of acute (primary) HIV infection
• Sexually transmitted disease
• Non-tender, discrete lymphadenophathy gt 2
  non-contiguous, non-inguinal nodes
• Unexplained cytopenias
• Oral candidiasis
• Refractory/recurrent vaginal candidiasis

61
HIV Testing Red Flags

• Skin lesions consistent with Kaposis Sarcoma
• Herpes zoster (shingles) in young, otherwise
  healthy patients
• Unexplained systemic symptoms fever, weight
  loss, diarrhea
• Unexplained recurrent bacterial infections
• History of possible exposure to HIV
  unprotected sex or needle-sharing with high-risk
  partner or partner of uncertain risk
• Patient concern/request

62
Resources

• USPHS Treatment Guidelines www.aidsinfo.nih.gov
• AIDS Education and Training Center (AETC)
  National Resource Center www.aidsetc.org
• CDC www.cdc.gov/hiv
• Fact sheets www.aidsinfonet.org

63
Resources

• National Network of Prevention Training Centers
  NNPTC
• http//depts.washington.edu/nnptc/
• Cincinnati STD/HIV Prevetnion Training Center
• www.stdptc.uc.edu

64
Questions?

• You may type your question here during the live
  presentation or call our
• Consultation Phone Line
• 1-800-459-2820
• Or Fax us at
• 513-357-7306

65
To Get your CMEs

• After viewing this eLearning Seminar, please go
  to our website, www.stdptc.uc.edu
• Sign in, look for the title of this seminar
• Follow directions to register
• Complete the evaluation
• Print out your CEU certificate!

66
HIV Primer for the Non-ID Clinician

• Jan M. Stockton, RN, MSN, AACRN
• University of Cincinnati
• AIDS Clinical Trials Unit
• stocktjm_at_uc.edu