Primary HIV1 Infection

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Primary HIV-1 Infection

• Donald Graves, M.D.
• Department of Family and Community Medicine
• University of California San Francisco
• National HIV/AIDS Clinicians Consultation Center

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Goals

• Understand the importance of Primary HIV from a
  historical and public health standpoint
• Be able to recognize the symptoms and signs of
  Primary HIV
• Understand which tests are important for its
  diagnosis
• Know where to refer patients when Primary HIV is
  suspected

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Primary HIV Infection

• 40,000 new cases are diagnosed per year in the US
• Studies estimate that as much as 87 of acute
  infections are symptomatic
• Acutely infected individuals might be responsible
  for up to half of new infections
• First described in 1984 in the case of a nurse
  accidentally infected by needle stick

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Case of Primary Infection?

• 32 year old man who has sex with men (MSM)
• Unprotected receptive anal sex without
  ejaculation
• Exposure 3 weeks ago
• 5 days of fever, muscle aches, fatigue, sore
  throat and malaise
• Denies rash, upper respiratory symptoms,
  arthralgias, weight loss, mouth sores
• Exam 38.7, mod swelling and erythema of tonsils,
  significant cervical lymphadenopathy and
  splenomegally

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What is the chance that this is primary HIV?

• Low
• Medium
• High

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Estimating the Risk of HIV Transmission in Your
Patient

• Type of behavior?
• Is source infected?
• Viral load of source?
• Presence of STD in exposed or sexual partner?

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Typical Risks of Exposures

• Exposure Estimated Average Per Contact
  Transmission Risk By Percentage
• Needle stick .3
• Shared needle .7
• Receptive anal sex .1-5
• Insertive anal sex .1
• Receptive vaginal .1-.2
• Insertive vaginal .1
• Receptive oral sex with Male .03-.06

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Symptoms Associated With Acute HIV Infection
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Symptoms Associated With Acute HIV Infection

• Symptom Incidence ()
• Fever 96
• Lymphadenopathy 74
• Pharyngitis 70
• Rash 70
• Myalgias or arthralgias 54
• Diarrhea 32
• Headache 32
• Nausea and vomiting 27
• Thrush 12
• Neurological disorders 12
• Adapted from Guidelines for Antiretroviaral
• and Nui

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Photos by Charles Farthing, Donald Abrams, and
Giant W. Morrows respectively from NEJM 7/2/1998
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Incubation period

• Intravaginal macaque/SIV model
• By 24 hours, SIV detected in the vaginal
  dendritic cells.
• By 48 hours, SIV detected in the vaginal lymph
  nodes.
• By 5 days, SIV can be detected in the blood.
• IN HUMANS, average time for HIV to be detected
  in the blood is about 4-11 days.

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Incubation period

• 2 week interval between exposure and symptoms is
  typical
• Usual range 1-4 weeks
• Cases outside range have been reported

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Summary of Estimated Risk of PHI in Case
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Summary of Estimated Risk of PHI in Case

• 32 year old gay man
• Unprotected receptive anal sex without
  ejaculation
• Exposure 3 weeks ago
• 5 days of fever, muscle aches, fatigue, sore
  throat and malaise
• Denies rash, upper respiratory symptoms,
  arthralgias, weight loss, mouth sores.
• Exam 38.7, mod swelling and erythema of tonsils,
  significant cervical lymphadenopathy and
  splenomegally

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Differential Diagnosis of PHI
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Differential Diagnosis of PHI

• EBV
• CMV
• HSV
• Rubella
• Varicella
• Syphilis
• Toxoplasmosis
• Viral Hepatitis
• Measles
• Disseminated GC

• Lyme disease
• Leptospirosis
• Typhus
• Typhoid fever
• Esophagitis
• Cryptosporidiosis
• Dengue
• Rocky mountain spotted fever
• Ehrlichiosis
• Infuenza
• Adenovirus
• Enteroviruses

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Test Results For Case

• HIV RNA 600 copies/ml
• HIV Ab West. Blot Negative
• Mono spot Positive
• RPR Pending
• CBC WBC 16, Atyp. Lymphs
• Transaminases Within Normal Limits

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Does the patient have primary HIV?

• Yes
• No
• Not sure

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Available tests for diagnosing PHI
Hecht, AIDS and Daar, Annals
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P24 Antigen

• Only test currently licensed for the detection of
  pre-seroconversion HIV
• Tests for the presence of viral core in the blood
• This test is used to screen all blood donations
  in the U.S.
• Can obtain same-day results.
• Cost can be as little as 20

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HIV RNA

• Not currently approved for the diagnosis of
  infection.
• There are two technologies, target amplification
  (PCR), signal amplification (bDNA, NASBA)
• False positive limit the use of these tests
• Very expensive

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Dynamics of laboratory tests during early HIV
infection
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Proposed Testing Algorithm
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Follow-up Test Results

• Repeat HIV RNA lt50
• RPR Negative
• GC/Chlam Negative

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Does the patient have primary HIV?

• Yes
• No
• Not sure

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Alternative Test Results

• HIV RNA 5,047,890 copies
• Repeat RNA similar
• HIV Antibody Negative
• CD4 270

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Does the patient have primary HIV?

• Yes
• No
• Not sure

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Treatment Decisions

• Would you treat this person?
• Do not offer HAART
• Offer HAART for a limited time period
• Offer HAART for an extended period

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Rationale for Treatment
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Rationale for Treatment

• Homogeneous Viral Population
• Reduce viral load and dissemination
• Preserve HIV specific immune response
• Delays development of opportunistic infections

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Potential Harms of Early Treatment
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Potential Harms of Early Treatment

• Drug toxicity
• Blunting of immunological response
• Development of resistance

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Studies Treatment of Primary HIV (PHI)

• 3 prospective primary HIV infection cohorts, 203
  patient.
• Group 1 Treatment during PHI symptoms (27 days
  between onset of symptoms and treatment)
• Group 2 Treatment after PHI symptoms (164 days
  between onset of symptoms and treatment
• Group 3 No treatment
• Results at the end of 3 years, there was no
  significant difference in the CD4 and viral load
  among all three groups

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Studies Treatment of Primary HIV (PHI)

• Walker and Rosenberg studied 14 individuals who
  were treated for PHI with ARVs. These
  individuals underwent supervised treatment
  interruptions . Data has been reported out to 5
  years. Failure was defined as a viral load gt
  5,000 for at least 3 consecutive months or a
  viral load gt 50,000 on any occasion. 11 patient
  were considered failures.

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Treatment

• Obtain Genotype Testing
• Refer to HIV Specialist or Primary HIV Study
• Medications

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Treatment

• Obtain Genotype Testing
• Refer to HIV Specialist or Primary HIV Study
• Medications

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Treatment

• Obtain Genotype Testing
• Refer to HIV Specialist or Primary HIV Study
• Medications

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Primary HIV Studies Bay Area

• Options Project
• Interleukin 2 study
• Pathogenesis
• Structured Treatment Interruptions
• Partner studies
• www.ucsf.edu/options
• http//clinicaltrials.gov/ct/show/NCT00001119?orde
  r3
• Acute HIV Infection and Early Disease Research
  Program (AIEDRP) AI-02-001
• http//clinicaltrials.gov/ct/show/NCT00001119?orde
  r3
• AIEDRP AI-01-001
• http//clinicaltrials.gov/ct/show/NCT00006441jses
  sionid754015D4A0E6673B719D70CDE74959C0?order3

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Treatment

• Obtain Genotype Testing
• Refer to HIV Specialist or Primary HIV Study
• Medications

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Medication Regimens

• 2 or 3 Nucleoside Reverse Transcriptase
  Inhibitors
• and
• 1 Protease Inhibitor or 1 Non-nucleoside Reverse
  Transcriptase Inhibitor or 1 Protease Inhibitor
  Boosted by Ritonivir
• 5 drug regimen, Interleukin-2, Z-100 are also
  under investigation
• Exact medication regimen or duration of
  medications is unknown!

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Conclusion

• Understand the importance of Primary HIV from a
  historical and public health standpoint
• Be able to recognize the symptoms and signs of
  Primary HIV
• Understand which tests are important for its
  diagnosis
• Know where to refer patients when Primary HIV is
  suspected