WHO Staging System for HIV/AIDS in ResourceHIV/AIDS in Resource

Limiting SettingsMasoud Mardani MD,MPH,FIDSA

Shahid Beheshti MedicalShahid Beheshti Medical University

Learning ObjectivesLearning Objectives

• Describe how the WHO staging system is usedDescribe how the WHO staging system is used to assist management of HIV/AIDS

• List the clinical conditions that characterize each WHO stage of HIV/AIDS

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The Natural History of HIV Infection

Pantaleo G, et al. N Engl J Med 1993;328;327.   

WHO Staging System for HIV/AIDS O iHIV/AIDS: Overview• Tool used to guide management of HIV patientTool used to guide management of HIV patient

in resource limited settings with limited laboratory access

• Clinically based; CD4 count not required• Simple, flexible and widely usedp , y• Recently revised: Interim African version 2005 • Utilizes 5 clinical stages based on the degree of Ut es 5 c ca stages based o t e deg ee o

immunocompromise and prognosis Primary HIV Infection, I,II, III, IV

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WHO Staging System for HIV/AIDS O i (2)HIV/AIDS: Overview (2)• Performed at each clinical visitPerformed at each clinical visit

DiagnosisEntry to clinical care (pre-ART)y (p )Follow-up

• Stage assessment can be adjusted upwards or downwards over time according to response to ART and/or clinical progression

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WHO Staging of HIV/AIDSWHO Staging of HIV/AIDS

• Primary HIV InfectionPrimary HIV Infection• Stage I - asymptomatic• Stage II - mild disease• Stage II - mild disease• Stage III - moderate disease• Stage IV advanced immunocompromise• Stage IV - advanced immunocompromise

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WHO Stage IWHO Stage I

• Asymptomatic orAsymptomatic or• Persistent generalized lymphadenopathy (PGL)

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Persistent Generalized Lymphadenopathy (PGL)y p p y ( )

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Courtesy of Charles Steinberg MD

WHO Stage IIWHO Stage II

• Moderate unexplained weight loss (<10% of presumed p g ( por measured body weight)

• Recurrent respiratory tract infections (RTIs, sinusitis, b hiti titi di h iti )bronchitis, otitis media, pharyngitis)

• Herpes zoster • Angular cheilitis• Angular cheilitis • Recurrent oral ulcerations • Papular pruritic eruptions p p p• Seborrhoeic dermatitis • Fungal nail infections of fingers

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Pruritic Papular Eruption (PPE)Pruritic Papular Eruption (PPE)

• EpidemiologyEpidemiology Substantial cause of HIV-related morbidity in sub-Saharan AfricaPrevalence ranges from 12-46%Uncommon in HIV negative patients (PPV of 82-87%; may play role in diagnosing HIV)may play role in diagnosing HIV)Probably related to hypersensitivity to arthropod bites

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Pruritic Papular Eruption (2)Pruritic Papular Eruption (2)

• Clinical ManifestationsIntensely pruritic, discrete, firm, papules; variable stages of developmentExcoriation results in pigmentation scarring andExcoriation results in pigmentation, scarring and nodules Predilection for extremities, but may involve trunk and faceSeverity of rash correlates with CD4 count

• Treatment• TreatmentTopical steroid and oral antihistamines; however often refractory

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Pruritic Papular Eruptionp p

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Courtesy of Charles Steinberg MD

Pruritic Papular Eruptionp p

13

Courtesy of Charles Steinberg MD

Apthous Ulcerp

14Source: www.HIVdent.org. Copyright © 1996-2000 David Reznik, D.D.S.

Herpes Zosterp

15Courtesy of Tom Thacher, MD Courtesy of the Public Health Image Library/CDC

Herpes Zosterp

16Courtesy of Samuel Anderson, MD

Molluscum Contagiosum g

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Oral Candidiasis

25Courtesy of Samuel Anderson, MD Courtesy of Dr. R. Ojoh

Oral Candidiasis (2)( )

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Source: http://members.xoom.virgilio.it/Aidsimaging

Aphthous LesionsClinical Typesyp

Minor (Lip) Minor (Tongue) Major

DHS/ HIV/PP

Oral Hairy leukoplakiay p

Courtesy of Dr. R. Ojoh

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WHO Stage IIIg

• Conditions where a presumptive diagnosis can be made th b i f li i l i i l i ti tion the basis of clinical signs or simple investigations Severe weight loss (>10% of presumed or measured body weight) Unexplained chronic diarrhea for > one monthUnexplained chronic diarrhea for > one month Unexplained persistent fever (intermittent or constant for > one month) Oral candidiasis Oral hairy leukoplakia Pulmonary tuberculosis (TB) diagnosed in last two years Severe presumed bacterial infections (e.g. pneumonia,

iti b j i t i f ti i itiempyema, pyomyositis, bone or joint infection, meningitis, bacteremia) Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis

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WHO Stage III (2)g ( )

• Conditions where confirmatory diagnostic testingConditions where confirmatory diagnostic testing is necessary

Unexplained anemia (<8 g/dl), and or neutropenia (<500/mm3) and or thrombocytopenia (<50 000/ mm3) for more than one

thmonth

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PyomyositisPyomyositis

• Large muscle groups, may be bilateralg g p , y• Pathophysiology unclear• Tends to occur with advanced HIV infection• Diagnosis requires:

High index of suspicionCT ultrasonographyCT, ultrasonography

• Staphylococcus aureus is the most commonly implicated organism

• Treatment usually requires needle aspiration and/or surgical incision and drainage in addition to intravenous antibiotics

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antibiotics

Pyomyositisy y

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Courtesy of Samuel Anderson, MD

WHO Stage IVWHO Stage IV

• Conditions where a presumptive diagnosis can be made p p gon the basis of clinical signs or simple investigations

HIV wasting syndrome Pneumocystis pneumoniaPneumocystis pneumonia Recurrent severe or radiological bacterial pneumonia Chronic herpes simplex infection (orolabial, genital or anorectal f th th’ d ti )of more than one month’s duration)

Oesophageal candidiasis Extrapulmonary TB Kaposi’s sarcoma Central nervous system (CNS) toxoplasmosis HIV encephalopathy

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HIV encephalopathy

WHO Stage IV (2)WHO Stage IV (2)

• Conditions where confirmatory diagnostic testingConditions where confirmatory diagnostic testing is necessary:

Extrapulmonary cryptococcosis including meningitis Disseminated non-tuberculous mycobacteria infection Progressive multifocal leukoencephalopathy (PML) Candida of trachea, bronchi or lungs Cryptosporidiosis I i iIsosporiasis Visceral herpes simplex infection

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WHO Stage IV (3)WHO Stage IV (3)

• Conditions where confirmatory diagnostic testingConditions where confirmatory diagnostic testing is necessary:

Cytomegalovirus (CMV) infection (retinitis or of an organ other than liver, spleen or lymph nodes) Any disseminated mycosis (e.g. histoplasmosis, coccidiomycosis penicilliosis)coccidiomycosis, penicilliosis) Recurrent non-typhoidal salmonella septicemia Lymphoma (cerebral or B cell non-Hodgkin)Lymphoma (cerebral or B cell non Hodgkin) Invasive cervical carcinoma Visceral leishmaniasis

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Severe Chronic Herpes Simplex Ulcersp p

37© Slice of Life and Suzanne S. Stensaas

Disseminated Cutaneous Cryptococcosisyp

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Courtesy of Samuel Anderson, MD

Disseminated cutaneous cryptococcosis (2)yp ( )

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Courtesy of Samuel Anderson, MD

HIV wasting syndromeHIV wasting syndrome

• Weight loss >10% body weightWeight loss 10% body weight plus

• Unexplained chronic diarrhea (>1 mo) or• Unexplained chronic diarrhea (>1 mo) or• Unexplained fever (>1 mo) plus chronic

weaknessweakness

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HIV encephalopathy (AIDS d ti l )(AIDS dementia complex)

• Dementia - persistent cognitive decline with preserved p g palertness

• Complex - concomitantly altered motor performance and, t ti b h i l th b i tat times, behavior; myelopathy may be prominent

• Disabling condition that interferes with activities of daily livingliving

• Progresses over weeks to months• Absence of concurrent illness or condition that could

explain findings• Limited treatment options; ART may be helpful

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Kaposi’s sarcomaKaposi s sarcoma

• Epidemiologyp gyHuman herpesvirus-8 (HHV-8) necessary but not sufficient for KS to developmost common AIDS-associated neoplasmmost common AIDS associated neoplasmincreased frequency in all HIV transmission groups compared to the general population

Cli i l if t ti• Clinical manifestations Variable, from an indolent process to a disseminated, aggressive diseaseskin lesions oral lesions others sites

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Kaposi’s Sarcoma: ManagementKaposi s Sarcoma: Management

• ART: an essential component of KSART: an essential component of KS management; lesions may regress

• Local irradiation: bulky/obstructive lesions (e.g. y ( goropharyngeal)

• Systemic IFN-alfa: slow progressive diseasey p g• Systemic chemotherapy: rapid, life threatening

disease including pulmonary or severe lymphedema

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Kaposi’s Sarcomap

46Courtesy of Tom Thacher, MD

IMMUNOLOGICAL STAGING OF HIV INFECTIONHIV INFECTION

• Clinical staging can be used effectively without access to CD4 or other laboratory testing.

• However, CD4 testing is useful for determining the degree g g gof immunocompromise, and where CD4 facilities are available they should be used to support and reinforce clinical decision-making.

• Data on CD4 levels are not a prerequisite for starting ART and should only be used in conjunction with consideration of the clinical stage. Presents

• CD4 levels is directly related to the severity of immunosuppression.

• For clinical purposes long term prognosis has been sho n to be related to the nadir or lo est e er al e ofshown to be related to the nadir or lowest-ever value of CD4.

• It should be noted that the immunological staging of disease reverses with successful ART.

• CD4 LEVELS IN RELATION TO THE SEVERITY OF IMMUNOSUPPRESSIONIMMUNOSUPPRESSION

• Not significant immunosuppression >500/mm3• Not significant immunosuppression >500/mm3• Mild immunosuppression 350 − 499/mm3• Advanced immunosuppression 200 −349/mm3Advanced immunosuppression 200 349/mm3• Severe immunosuppression <200/mm3

• Clinical and Immunological Criteria for• Clinical and Immunological Criteria for Initiating ART in Adult

• Clinical stage ART:• Clinical stage ART:

4 T• 4 Treat.• 3 Consider treatment: CD4, if available, can guide

the urgency with which ART should be started.• 1 or 2 Only if CD4 <200/mm3.

When to start?

• Not too early • Not start too lateNot too early Not start too late

Key PointsKey Points

• WHO Staging of HIV/AIDS is an important toolWHO Staging of HIV/AIDS is an important tool used for management of HIV in resource limited settings

• Staging is based on clinical conditions that correlate with the degree of immunocompromise and prognosis

• Staging should be assessed at time of HIV di i i i ART d i h hdiagnosis, prior to starting ART, and with each follow-up visit to assess response to ART

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