Natural History and
Clinical Staging of HIV Infection
Natural History of HIV
Session Objectives
By the end of the session the participant will be able
• To list the modes of HIV transmission
• To discuss the pathogenesis and life cycle of HIV
• To describe the progression of HIV
• To classify an HIV-infected patient according to the WHO clinical staging
Natural History of HIV 2
Semen and Vaginal Fluids
Sharing Needles
& Syringes
Through Infected Blood
During Pregnancyor Birth
Breast Feeding
Images Courtesy HIV Basics Course for Nurses, I-TECH
Needle StickInjury
Modes of HIV Transmission
Natural History of HIV 3
Exposure Route HIV Transmission
Blood transfusion 90-95%
Perinatal 20-40%
Sexual intercourse 0.1 to 1%
Vaginal 0.05-0.1%
Anal 0.065-0.5%
Oral 0.005-0.01%
Injecting drugs use 0.67%
Needle stick exposure 0.3%
Mucous membrane splash to eye, oro-nasal
0.09%
Source: NACO PEP Guidelines
HIV Transmission Risk
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How HIV Infects the Body
Exponential viral replication
Widespread systemic dissemination to the brain, spleen, distant lymph nodes, etc.
(5-11 Days)
HIV makes contact with cells located within the genital mucosa
Virus is carried to regional lymph nodes (1-2 Days)
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Image Courtesy Kahn JO, Walker BD. NEJ Med.1998; 339: 33-39
Exposure to HIV atmucosal surface (sex)
Virus collected by dendritic cells, carried to lymph node
HIV replicates in CD4 cells, released into blood
Virus spreads to other organs
Day 0
Day 0-2
Day 4-11
Day 11 on
Path of the Virus
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Image Courtesy HIV Basics Course for Nurses, I-TECH
HIV Lifecycle Video
HIV Lifecycle
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Viral transmission
Acute retroviral syndrome: 2-3 weeks
Seroconversion: 2-4 weeks
Asymptomatic chronic HIV infection: 8 yrs (Avg.)
Symptomatic HIV infection/AIDS: 1.3 yrs (Avg.)
Stages of Untreated HIV Infection
Natural History of HIV 8
10^6
10^2
HIV RNA Copies/ml
1 3 about 6mths // 5yrs 10 yrs
Acute HIV
Opportunisticinfections
Asymptomatic
Minor HIV-relatedsymptoms
Virologic set-point Varies from patient to
patient
HIV antibodiesAcute HIV800
200
HIV antibodies
CD4 countcells/µl
Time
Typical Course of Untreated HIV Infection
Death
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• Acute Seroconversion (Acute HIV Syndrome)
• Asymptomatic HIV (Clinical latency)
• Symptomatic HIV
• Acquired Immune Deficiency Syndrome (AIDS)
Natural History of HIV
Progression of HIV Disease
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Acute HIV syndrome
• Transient symptomatic illness
• Affects 40-90% of HIV+ individuals
• Ranges from mild, non-specific illness to severe illness that can result in hospitalisation
Natural History of HIV 11
HIV Web study (www.HIV webstudy.org) Supported by HRSA
Acute HIV syndrome: Clinical Manifestations
Natural History of HIV
Courtesy: Walker, B. 40th IDSA, Chicago 2002.
Small pink macules: Trunk, limbs and faceCourtesy: Kahn, NEJM, 1998
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Patterns of HIV Progression
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• Typical progressors
• Rapid progressors
• Slow progressors
• Long-term non-progressors
WHO Clinical Staging
• WHO Clinical Staging 1
• Asymptomatic
• Persistent generalised lymphadenopathy (PGL)
• Painless enlarged lymph nodes >1 cm• In two or more non-contiguous sites (excluding
inguinal), in absence of known cause and• Persisting for 3 months
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WHO Clinical Staging 2 Unexplained moderate weight loss
(<10% of presumed or measured body weight)
Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media, pharyngitis)
Herpes zoster
Angular cheilitis
Recurrent oral ulceration
Papular pruritic eruptions (PPE)
Seborrhoeic dermatitis
Fungal nail infections
Natural History of HIV 15
WHO Clinical Staging 3 Unexplained severe weight loss
(>10% of presumed or measured body weight)
Unexplained chronic diarrhoea for longer than one month
Unexplained persistent fever (above 37.5oC intermittent or constant for longer than one month)
Persistent oral candidiasis
Oral hairy leukoplakia (OHL)
Pulmonary tuberculosis
Natural History of HIV 16
WHO Clinical Staging 3 Severe bacterial infections (e.g. pneumonia,
empyema, pyomyositis, bone or joint infection, meningitis, bacteraemia)
Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis
Unexplained
Anaemia (<8 g/dl)
Neutropenia (<0.5 x 109 /L) and or
Chronic thrombocytopenia (<50 X 109 /L)
Natural History of HIV 17
WHO Clinical Staging 4 HIV wasting syndrome
Pneumocystis pneumonia (PCP)
Recurrent severe bacterial pneumonia
Chronic herpes simplex infection (orolabial, genital or anorectal of more than one month’s duration or visceral at any site)
Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
Extra pulmonary tuberculosis
Kaposi’s sarcoma
Natural History of HIV 18
WHO Clinical Staging 4 Cytomegalovirus infection
(retinitis or infection of other organs)
Central nervous system toxoplasmosis
HIV encephalopathy
Extra pulmonary cryptococcosis including meningitis
Disseminated non-tuberculous mycobacteria infection
Progressive multifocal leukoencephalopathy
Chronic cryptosporidiosis
Chronic isosporiasis
Natural History of HIV 19
WHO Clinical Staging 4 Disseminated mycosis (extra pulmonary
histoplasmosis, coccidiomycosis)
Recurrent septicaemia (including non-typhoidal salmonella)
Lymphoma (cerebral or B cell non-Hodgkin)
Invasive cervical carcinoma
Atypical disseminated leishmaniasis
Symptomatic HIV associated nephropathy or Symptomatic HIV associated cardiomyopathy
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WHO Clinical Staging
Case Studies (17)
Natural History of HIV
• Each trainee has to discuss one case study
• Look into the clinical photograph / X-ray
• Describe the lesion, as you observe
• Discuss Differential Diagnosis
• Identify Clinical staging of HIV infection
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Case Study 1 and 2
Natural History of HIV
Source: GHTM, Tambaram, Chennai
• Describe the lesion• Identify Clinical staging of HIV infection
22
Case Study 3
Natural History of HIV
Source: GHTM, Tambaram, Chennai
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WHO Clinical Staging in CLHIV
Image Courtesy: GHTM/ITECH Fellowship Programme, Tambaram, Chennai
Case Study 4
24
Case Study 5 & 6
Image Courtesy :GHTM, Tambaram, Chennai
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OI Curriculum, GHTM-I-TECH, 2004
Images Courtesy: I-TECH-GHTM Fellowship Programme, Tambaram, Chennai
Natural History of HIV 26
Case Study 7
Image Courtesy: Bowring Hospital, Bangalore
Case Study 8
Natural History of HIV
• Describe the lesion
• What are the differential diagnosis?
• Clinical staging?
27
Image Courtesy
GHTM , Tambaram
HIV Fellowship Programme
Natural History of HIV 28
Case Study 9
Case Study 10
Images Courtesy: GHTM/ITECH Fellowship Programme, Tambaram, Chennai
WHO Clinical Staging in CLHIV29
Case Study 11 Case Study 12
Images Courtesy: Indian Academy of Pediatrics
WHO Clinical Staging in CLHIV30
Image Courtesy: Indian Academy of Pediatrics
Case Study 13
WHO Clinical Staging in CLHIV31
Case Study 14
WHO Clinical Staging in CLHIV
Image Courtesy: GHTM/ITECH Fellowship Programme, Tambaram, Chennai
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Case Study 15
• 5 year old child
• Respiratory distress
• Cough+
• No sputum
• Respiratory Rate: 45/mt
• Lung signs: Bilateral basal inspiratory crackles
Image courtesy: TRC, Chennai
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• 37 year-old HIV positive male
• Lost 9 kg in last 3 months (Previously his body weight was 75 kg)
• Reports having a fever for the past month
• Treated for pulmonary TB 5 months ago
What is his WHO clinical staging?
Case Study 16
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• 34 year-old HIV positive male
• Suffers from bacterial sinusitis and a fungal infection on his toes
• Has no problem keeping up with his usual activities and weight is stable
• Treated for herpes zoster 4 years ago
What is his WHO clinical staging?
Case Study 17
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Key Points
• The most common mode of HIV transmission in India is sexual
• Understanding the natural history of HIV is important in predicting progress of the disease
• Clinical staging allows clinicians to reliably predict in patients:
– The risk of opportunistic infections and death
– The need for disease prevention & pre ART Care
– ART Initiation
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