Natural history of HIV infection

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Natural history of HIV infection
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The Normal lmmune System

• Protects the body
• Consists of lymphoid organs and tissues
• All of its components are vital in the production
  and development of lymphocytes
• B-cells and T-cells are produced from stem cells
  in the bone marrow
• B-cells recognize specific antigen targets and
  secrete specific antibodies

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The Normal lmmune System, continued

• T-cells regulate the immune system and kill cells
  that bear specific target antigens
• CD4 cells are helper cells that activate
  B-cells, CD8 and macrophages when a specific
  antigen is present
• When the immune system is weakened or destroyed
  by a virus such as HIV, the body is vulnerable to
  opportunistic infections (OIs)

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HIV Lifecycle

• Host cells infected with HIV have a very short
  lifespan.
• HIV continuously uses new host cells to replicate
  itself.
• Up to 10 million individual viruses are produced
  daily.
• During the first 24 hours after exposure, the
  virus attacks or is captured by dendritic cells
  (type of phagocyte) in mucous membranes and skin.
  
• Within five days of exposure, infected cells make
  their way to lymph nodes and then to the
  peripheral blood, where viral replication becomes
  very rapid.

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Stages of HIV infection

• Viral transmission 2-3 wks.
• Acute Retroviral syndrome 2-3 wks.
• Recovery Seroconversion 2-4 wks.
• Asymptomatic chronic HIV infection Avg. 8 yrs
• Symptomatic HIV infection / AIDS Avg. 1.3 yrs

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HIV AIDS The cellular immunological picture
The course of the disease

• This time course of HIV infection applies to
  persons not receiving chemotherapy

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Primary HIV Infection and Seroconversion

• Clinical Features
• On first exposure, there is a 2-4 week period of
  intense viral replication before the onset of an
  immune response and clinical illness.
• Acute illness lasts from 1-2 weeks and occurs in
  53 to 93 of cases.
• Clinical manifestations resolve as antibodies to
  the virus become detectable in patient serum.
• Patients then enter a stage of asymptomatic
  infection lasting months to years.

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Primary Infection
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Stages of Disease Progression

• Early Immune Depletion (CD4 cell count gt 500/mL)
• During this stage, level of virus in blood is
  very low
• HIV replication taking place mostly within lymph
  nodes
• Generally lasts for five years or more
• Persistent Generalized Lymphadenopathy (PGL)
  without other symptoms may be noted
• Usually symptom-free, but several autoimmune
  disorders may appear

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Stages of Disease Progression, continued

• Intermediate Immune Depletion
• (CD4 cell count between 500 and 200/ mL)
• Immune deficiency increases
• Infections commence and persist or increase as
  the CD4 cell count drops
• Consider preventive treatment for TB and
  Cotrimoxazole Prophylaxis
• Less severe infections, particularly of skin and
  mucosal surfaces, appear
• Other infections begin to manifest

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Stages of Disease Progression, continued

• Advanced Immune Depletion (CD4 cell lt200/ mL)
• Case definition of AIDS is having a CD4 cell
  count of less than 200/ mL

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Patterns of CD4 Cell Decline

• Slow or
• Non-decliners
• (long-term
• non-progressesors)

• Moderate
• decliners
• 35-50 cell drop
• per year

• Rapid prog-
• essors
• ("CD4
• crash")
• 50 cell drop
• per month

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Opportunistic Infections

• Protozoal toxoplasmosis, cryptosporidosis
• Fungal candidiasis, cryptococcosis
• histoplasmosis, pneumocystis carinii
• Bacterial Mycobacterium avium complex
• atypical mycobacterial disease
• salmonella septicaemia
• multiple or recurrent pyogenic bacterial
  infection
• Viral CMV, HSV, VZV, JCV

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Common OIs in India

• Recurrent bacterial infections
• Tuberculosis
• Candidiasis
• Chronic diarrhoea
• Cryptococcosis
• Pneumocystis carinii pneumonia
• Toxoplasmosis

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Opportunistic Tumours

• Kaposis Sarcoma is observed mostly in
  homosexuals. It is associated with a human herpes
  virus 8 (HHV-8).
• Malignant lymphomas are also frequently seen in
  AIDS patients.

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Other Manifestations

• It is now recognised that HIV-infected patients
  may develop a number of manifestations that are
  not explained by opportunistic infections or
  tumours.
• The most frequent neurological disorder is AIDS
  encephalopathy which is seen in two thirds of
  cases.
• Other manifestations include characteristic skin
  eruptions and persistent diarrhoea.

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Oral Candidiasis

• Symptoms thrush, sore mouth
• Pseudomembranous, atrophic, hyper-plastic,
  angular cheilitis
• Treatment Nystatin, Fluconazole

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Oesophageal Candidiasis

• 1/3 of AIDS pts develop esophageal symptoms
  (dys-phagia, odynophagia) 50-70 due to Candida
  oral thrush in 50-70
• Usually treated empirically endo-scopy biopsy,
  with HPE cultures, if no response in 7-10 days

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Focal neurological Deficit 80 Seizure
30 Evolution lt2 wk
Basal ganglia Multiple Ring enhancement Not much
edema
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Cryptococcus
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CMV
BLURRING, BLIND SPOTS FLASHES Fluffy white
lesions Hemorrhages close to vessels
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Prophylaxis

• Infection Indication Drug

• P.Carinii
  CDlt200
• previous PCP
• WHO stage 34 Co-
  trimoxazoleDS 1 od
• Toxoplasma previous Toxo Co-
  trimoxazoleDS 1 od
• Co trimoxazole reduces
• Resp infn,,
  diarrhoea.,toxoplasmosis

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WHO staging system for HIV infection
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WHO staging contd

• Clinical stage III
• Weight loss gt10 of body weight
• Unexplained chronic diarrhea gt 1 month
• Unexplained prolonged fever (intermittent or
  constant) gt 1 month
• Oral candidiasis (thrush)
• Oral hairy leukoplakia
• Pulmonary tuberculosis
• Severe bacterial infections (pneumonia,
  pyomyositis)
• and/or performance scale 3 bed-ridden, lt50 of
  the day during past month
• Clinical stage IV
• AIDS-defining illness
• and/or performance scale 43 bed-ridden, gt50 of
  the day during past month

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Some Clinical Features Suspicious/suggestive of
HIV infection
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The Clinical diagnosis of HIV infection
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Basic principles

• HIV is a Treatable disease-HIV should not kill
• Discrimination at health care setting EQUALLY or
  more dangerous than OIs (third epidemic)
• Almost all OIs are treatable
• Many important OIs are preventable

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Post exposure prophylaxis

• Pre exposure prophylaxis
• Remember at least 3 blood borne pathogens
• Hep B,C,HIV

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Efficiency of different routes of HIV transmission

• Exposure Route Per cent Efficiency
• Blood transfusion 90-95
• Perinatal 20-40
• Sexual intercourse 0.1 to 1
• Injecting drugs use 0.5 1.0
• Needle stick exposure lt0.5

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Who is at risk?

• Lab tech
• Nurses
• Physicians
• Surgeons
• ..

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After exposure

• Report it
• Classify the source and exposure
• Get PEP if necessary
• Follow up

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High risk

• High viral load, advanced disease
• Deep injury
• Instruments deep in the artery and vein
• Large amount of blood
• Hollow needle

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Low risk

• Superficial injury
• Minimal contact
• Asymptomatic patient with low viral load
• Mucosal exposure

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No Risk

• Intact skin exposures

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PEP

• Basic regimen
• Zidovudine 300 mg bdLamivudine 150 mg bd x 28
  days

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• Extended regimen
• Zidovudine 300 mg bdLamivudine 150 mg
• Q12 h
• Indinavir 800 mg Q8H
• x 28 days

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