Clinical Presentation and WHO

Clinical Staging

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 Session Objectives

By the end of the session participants will be able to:

• List the presentation of acute/primary HIV

infection

• List the differential diagnosis for acute/primary HIV

infection

• Classify stage of HIV infection based on the WHO

clinical classification systems
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 Patient Clinical Presentation (1)
• Thorough interview

• Physical examination include:

–Oral thrush
–Macular rash on palate as a sign of Kaposi
sarcoma
–Herpes zoster scar

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 Patient Clinical Presentation (2)
• Physical examination include:
–Florid nature of skin manifestations, a hallmark
of HIV
–Condition of the pectoralis, temporalis, biceps,
gluteus and shin cover muscles as a clue to
wasting
–Lymphadenopathy, usually not >2.5 cm

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Primary HIV Infection and Seroconversion
Clinical features
– A 2-4 week period of intense viral replication before
onset of clinical illness.
– An acute febrile illness (53% to 93%) 2-4 weeks
after infection ; lasts 1-2 weeks
– Clinical manifestations resolve as antibodies to virus
become detectable in patient serum.
– Patients then enter a stage of asymptomatic
infection ( months to years.)

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 Seroconversion Illness (1)
• Manifests as a flu-like syndrome

• General symptoms may include:

– Acute onset of fever with or without night sweats
– Myalgia, may be associated with muscle
weakness
– Lethargy and malaise
– Depressed mood
– Pharyngitis/sore throat

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 Seroconversion Illness (2)
• General symptoms may include:
– Maculopapular rash
– Orogenital ulcers
– Lymphadenopathy
– Arthralgia
– Anorexia/weight loss

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 Seroconversion Illness (3)

Neurological symptoms

• Headache

• Photophobia

• Retro-orbital pain

• Early infection : aseptic meningoencephalitis

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 Seroconversion illness (4)

Other more unusual features include:

• Myelopathy

• Peripheral neuropathy

• Brachial neuritis

• Facial palsy

• Guillain-Barre syndrome

• Meningoencephalitis
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 Seroconversion Illness (5)
Gastrointestinal symptoms
• Mucocutaneous ulceration is a distinctive feature
• Ulcers are generally small, round or oval.
• Surrounding mucosa looks normal.
• Pharyngeal edema is common.
• Oral/oropharyngeal candidiasis
• Nausea/vomiting
• Diarrhea

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 Seroconversion Illness (6)
Dermatological symptoms
• Erythematous, non-pruritic, maculopapular rash is
common.
• Roseola-like rash
• Diffuse urticarias
• Desquamation of palms and soles
• Alopecia
• Lymphadenopathy
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 Laboratory Findings (1)
First 1-2 weeks:
• Lymphopenia ,reduction in CD4 and CD8 counts

• Followed by a peripheral lymphocytosis.

• Mild thrombocytopenia

• Elevated C-reactive protein level and erythrocyte

sedimentation rate.

• Elevated serum alkaline phosphatase and transaminase

levels
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 Laboratory findings (2)
First 2-6 weeks:
• Antibodies to HIV may not yet be detectable.
• HIV antigen detected in serum before detecting
antibodies (antigen testing is important in diagnosing
seroconversion.)
• The window period:
– HIV-positive patients may not test positive for
anti-HIV antibodies.
– limited to first 2-6 weeks,
– Repeat testing after 2-6 weeks is recommended.
– In rare cases, the window period may last as long
as 6-12 months.
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 Differential Diagnosis of Acute/Primary
HIV Infection (1)
• Epstein-Barr virus mononucleosis

• Cytomegalovirus mononucleosis

• Toxoplasmosis

• Rubella

• Syphilis

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 Differential Diagnosis of Acute/Primary
HIV Infection (2)
• Viral hepatitis

• Primary herpes simplex virus infection

• Disseminated gonococcal infection

• Other viral infections

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 Management of Acute HIV Infection (1)

• Symptomatic

• Appropriate counseling and education to prevent

further spread

• ART if HIV status is confirmed

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 Management of Acute HIV Infection (2)
• Issues to consider:

– The physical distress of the illness

– Tentative nature of the diagnosis before sero-

diagnosis is made

– Patient’s psychological state

– implications for the patient’s lifestyle

– Contact tracing should be attempted to identify the

source.
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 Group discussion of Acute
Infection in the Nepal Setting
including available diagnostics

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 Case Study
Laxmi, a 28 year old woman from Bajura District,
comes to see you complaining of 4 days of sore throat,
fever, rash and headache. She is a newly wed, married
5 months ago to a man who regularly travels to India
for work.

• Physical examination shows: Temperature of 37.8C

• Maculopapular rash on trunk
• Erythematous oropharynx
• White plaque-like lesions on the buccal mucosa

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 Case Study
• What is in your differential diagnosis?
• Why is her social history important?
• What further investigations would you perform?
• What is the most likely diagnosis, given non-specific
laboratory findings?
• What treatment would you offer?
• How would you counsel this patient?
• What are other symptoms of this suspected illness?

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 Clinical Presentation of Chronic HIV
• Usually asymptomatic for many years.

• HIV progresses clinically as immunodeficiency

develops.

• Some PLHIV remain clinically well until very

advanced immunosuppression has developed, while
others become ill, when CD4 is still relatively high.

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 Follow-up Visits After Testing HIV
Positive
New on ART: Only just initiating ART and are within six months of commencing ART
• First Month: two visits (every 2 weeks)
• Second and third month: two visits (every month)
• Fourth month onwards: one visits every three months
Stable on ART: on ART for greater than 12 months, no incidence OI in preceding 6
months), self-reported medication adherence (>90%), adherence to clinic
appointments (>90%), response to ART with increased CD4 and or suppressed viral
load, clinical visits every 3 months and pill pick up every 3 months

• Not stable on ART: Clients with treatment failure, poor adherence, OIs and
adverse effects. In addition, those at risk of being lost to follow up or returning
after being lost to follow up also fall into this category
• These clients should be followed up more frequently as in first three months. Viral
load should be done as indicated and client should be referred for consultation
with ART clinician for possible change in ART regimen.
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 Subsequent Visits (1)
• Ongoing education about HIV/ AIDS and positive
living
• Positive prevention methods
• Questions about pregnancy or unmet family planning
needs at each visit
• Ongoing psychosocial counseling or referrals
• Intensive patient treatment literacy education and
recruitment of family member or other treatment
supporter

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 Subsequent Visits (2)
• Diagnosis, treatment and prevention of opportunistic
infections
• WHO Clinical Staging at every visit
• CD4 count every 6 months
• TB screening using questionnaires at every visit

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 WHO Staging (Clinical and Immunological):
Overview (1)

– WHO Clinical staging used once HIV infection has been

confirmed by laboratory testing.

– For babies <18 months with no PCR results, presumptive

clinical diagnosis of severe HIV disease can be made

– Useful for assessment at baseline (first diagnosis of HIV

infection) and in the follow-up of patients

(Ref: WHO Staging guidelines 2007)

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WHO Staging (Clinical and Immunological):
Overview (2)
– Guide decisions on when to start cotrimoxazole
prophylaxis
– Clinical stages have been shown to be related to
survival, prognosis and progression of clinical
disease

– Where laboratory monitoring is available, CD4 cell

count is essential in determining immunological
status

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 The WHO Clinical Staging System (1)

WHO clinical
HIV-associated symptoms
stage

Asymptomatic 1

Mild symptoms 2

Advanced symptoms 3

Severe symptoms 4

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 The WHO Clinical Staging System (2)
• Categorize the immunosuppression based on which
clinical illnesses the patient has had.

• Helps predict morbidity and mortality.

• Clinical markers fall into four stages of prognostic

significance and form the basis of the WHO Clinical
Staging System.

• There is a separate Clinical Staging system for

pediatric use, with subtle but important differences.
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 WHO Clinical Staging System (3)

Clinical Stage 1 (Asymptomatic)

Asymptomatic infection

Persistent generalized lymphadenopathy (enlarged

nodes in at least 2 areas of the body for 3 months or
longer)

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 WHO Clinical Staging System (4)
Clinical Stage 2 (Mild disease)
Unexplained moderate weight loss (<10% of presumed
or measured body weight)

Recurrent respiratory tract infections (sinusitis,

tonsillitis, otitis media and pharyngitis)

Herpes zoster

Angular cheilitis

Recurrent oral ulceration

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 WHO Clinical Staging System (5)
Clinical Stage 2 (Mild disease)
Pruritic papular eruptions (PPE)

Seborrhoeic dermatitis

Fungal nail infections

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 WHO Clinical Staging System (6)
Clinical Stage 3 (Moderate disease)
Unexplained severe weight loss (>10% of presumed or
measured body weight)
Unexplained chronic diarrhea for longer than one
month
Unexplained persistent fever (above 37.5°C intermittent
or constant, for longer than 1 month)
Persistent oral candidiasis
Oral hairy leukoplakia
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 WHO Clinical Staging System (7)
Clinical Stage 3 (Moderate disease)
Pulmonary tuberculosis
Severe bacterial infections (such as pneumonia,
empyema, pyomyositis, bone or joint infection,
meningitis or bacteremia)
Acute necrotizing ulcerative stomatitis, gingivitis or
periodontitis
Unexplained anemia (<8 g/dl), neutropenia (<0.5 × 109
per liter) and/or chronic thrombocytopenia (<50 × 109
per liter)
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 WHO Clinical Staging System (8)
Clinical Stage 4 (Severe Disease)
HIV wasting syndrome

Pneumocystis pneumonia

Recurrent severe bacterial pneumonia

Chronic herpes simplex infection (orolabial, genital or

anorectal of more than one month's duration or visceral
at any site)

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 WHO Clinical Staging System (9)
Clinical Stage 4 (Severe Disease)
Oesophageal candidiasis (or candidiasis of trachea,
bronchi or lungs)

Extrapulmonary tuberculosis

Kaposi sarcoma

Cytomegalovirus infection (retinitis or infection of other

organs)

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 WHO Clinical Staging System (10)
Clinical Stage 4 (Severe Disease)
Toxoplasmosis of central nervous system

HIV encephalopathy
Extrapulmonary cryptococcosis including meningitis
Disseminated non-tuberculous mycobacterial infection
Progressive multifocal leukoencephalopathy
Penicillinosis

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 WHO Clinical Staging System (11)
Clinical Stage 4 ( Severe disease)
Chronic cryptosporidiosis
Chronic isosporiasis
Disseminated mycosis (extrapulmonary histoplasmosis or
coccidiomycosis)
Recurrent septicaemia (including non-typhoidal
Salmonella)
Lymphoma (cerebral or B-cell non-Hodgkin)

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 WHO Clinical Staging System (12)
Clinical Stage 4 ( Severe disease)

Invasive cervical carcinoma

Atypical disseminated leishmaniasis
Symptomatic HIV-associated nephropathy or
symptomatic HIV-associated cardiomyopathy

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 Case Study #1

Bharat, a 35 year old truck driver from Damak, comes

to the clinic complaining of persistent diarrhea that
started 5 months ago. Stool exam reveals
cryptosporidium.

• In what WHO Stage is this patient?

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 Case Study# 2

Sangita, a young woman from Jhapa comes to the clinic

complaining of unexplained fever and weakness for
over a month. From her previous record you see that
six months ago she weighed 54kg. She now weighs 46
kg. She has a history of herpes zoster and a positive
HIV antibody test.

• Based on symptoms and history what clinical stage

is she in?

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 Case Study# 3

Sabina is a 22-year-old woman. She is HIV positive. She

thinks she got HIV when she was a teenager after being
forced to go to India for work. She has repeated middle
ear infections, and lost some weight, but not a lot. She
has no other clinical signs.

• What clinical stage is Sabina in now?

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 Continuation of Case Study# 3
Sabina comes to the consultation with blisters on one
side of the chest. It is really painful. It started 2 days
ago. In the mean time, Sabina’s family makes plans for
her to marry. She would like to have children in the
future, but not now. She is using oral contraception.
Sabina wants some treatment for her very painful
blisters.
Questions on Sabina:
• What clinical stage is she on this visit?
• What treatment would you give her?
• What questions and counseling is needed
concerning her proposed marriage?
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 Case Study #4
Kato is a 27-year-old ex-PWID. After a successful
recovery program, he was selling some small
household material in the street to make a living, but
now he is so sick he cannot work anymore. He is very
weak and has to stay in bed most of the time. He is
very thin and has had fever continuously for several
months. He was worried about having AIDS for a long
time, but has never had the courage to do a test. Now,
he heard about free ART, and finally did the test. He
tested HIV positive.

• In what clinical stage is Kato?

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 Case Study #5
Mr. Ram is a businessman. He is 40 years old. He has a
nice house and lives in Kathmandu. His wife died 2
years ago. He has 2 young children ages 4 and 6 years,
who are in good health. He has a new wife. Now, his
weight has dropped from 75 kg to 73 kg, and he starts
to have an itchy rash on his arms and legs.

• What could you suggest to Mr. Ram?

• In what clinical stage is Mr. Ram?

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 Thank You

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