1. WHO Staging System for HIV/AIDS in Resource Limiting Settings
Unit 5
HIV Basics: A Course for Physicians
Unit 5 should take approximately 60 minutes to implement
Step 1: Unit Overview and Learning Objectives (Slides 1 – 2) – 5 minutes
Step 2: Clinical Stages of HIV Disease (Slides 3 – 40) – 30 minutes
Step 3: Case Studies - Clinical Staging of HIV Patients (Slides 41 – 49) – 20 minutes
Step 4: Summary of Key Points (Slide 50) – 5 minutes

2. Learning Objectives
Describe 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
Step 1: Unit Overview and Learning Objectives (Slides 1 – 2) – 5 minutes

3. Introductory Case: Lake
33 year old male presents to ART clinic for initial evaluation. He has a history of Zoster. He reports diarrhea, intermittent fever, and itching. He stopped working as a merchant one month ago due to fatigue.
What additional information is necessary for accurate WHO staging of this patient?
Step 2: Clinical Stages of HIV Disease (Slides 3 – 40) – 30 minutes
Additional question for the participants: Why is staging important for the management of this patient?

4. Introductory Case: Lake (2)
Diarrhea occurred daily, was non-bloody, and began 2 months ago
Fever began 2 months ago
Wt loss of 8 kg (50 ->42kg) over last 6 months
History of PTB treatment 1 year ago
No cough, night sweats
Exam revealed thrush and papular rash on trunk and extremities
CXR normal
Stool exam normal
HCT 9 g/dl
Based on these finding, the patient meets criteria for HIV wasting syndrome, placing him in WHO stage IV.
Chronic unexplained diarrhea, fever, and weight loss independently are stage III defining conditions as is PTB diagnosed within the last two years, and thrush.
What condition in this patient is a WHO stage II defining illness? (PPE)

5. WHO Staging System for HIV/AIDS: Overview
Tool 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 used
Recently revised: Interim African version 2005
Utilizes 5 clinical stages based on the degree of immunocompromise and prognosis
Primary HIV Infection, I,II, III, IV
It is used in Ethiopia to assist with clinical decision-making, such as decisions on starting, substituting, switching, and stopping ART.
It originally allowed for “down-staging” only (e.g. Stage II->III) in light of the natural progression of HIV infection, with no reversal or improvement allowed.
The latest revision, however, allows for bi-directional staging over time, recognizing that ART can change the prognosis of patients and block the inevitable progression to AIDS.

6. WHO Staging System for HIV/AIDS: Overview (2)
Performed at each clinical visit
Diagnosis
Entry to clinical care (pre-ART)
Follow-up
Stage assessment can be adjusted upwards or downwards over time according to response to ART and/or clinical progression
Assessment of clinical stage at each clinical visit also provides useful information on current clinical status, and can guide clinical decision making.
The ability to modify WHO stage over time reflects the most recent WHO revision. But this may require judgment. For example, what is the stage of an otherwise healthy HIV patient who has fully recovered from PCP two weeks ago. (Is this patient stage I or IV??)

7. WHO Staging of HIV/AIDS
Primary HIV Infection
Stage I - asymptomatic
Stage II - mild disease
Stage III - moderate disease
Stage IV - advanced immunocompromise
The following slides will review the specific conditions that comprise each stage. Primary HIV infection will be discussed in a different section.

8. WHO Stage I Asymptomatic or
Persistent generalized lymphadenopathy (PGL)

9. Persistent Generalized Lymphadenopathy (PGL)
Swollen glands (>1cm) in two or more areas outside the groin, >3mo
Lymph nodes are firm, painless
Occurs in the back of neck, under the jaw, and in armpit
What is the differential diagnosis of this finding? (TB, lymphoma, bacteria)
Courtesy of Charles Steinberg MD

10. WHO Stage II
Moderate unexplained weight loss (<10% of presumed or measured body weight)
Recurrent respiratory tract infections (RTIs, sinusitis, bronchitis, otitis media, pharyngitis)
Herpes zoster
Angular cheilitis
Recurrent oral ulcerations
Papular pruritic eruptions
Seborrhoeic dermatitis
Fungal nail infections of fingers

11. Pruritic Papular Eruption (PPE)
Epidemiology
Substantial cause of HIV-related morbidity in sub-Saharan Africa
Prevalence ranges from 12-46%
Uncommon in HIV negative patients (PPV of 82-87%; may play role in diagnosing HIV)
Probably related to hypersensitivity to arthropod bites
Some clinical conditions, such as PPE, are reviewed here because they are not covered in the OI section and is particularly common in Ethiopia.
The differential diagnosis includes scabies, which can be difficult to differentiate. Scabies tends to involve the web of fingers, groin, underarms, and breast areas, but can be diffuse.. Often it is reasonable to treat empirically for scabies if the diagnosis is at all in question.

12. Pruritic Papular Eruption (2)
Clinical Manifestations
Intensely pruritic, discrete, firm, papules; variable stages of development
Excoriation results in pigmentation, scarring and nodules
Predilection for extremities, but may involve trunk and face
Severity of rash correlates with CD4 count
Treatment
Topical steroid and oral antihistamines; however often refractory

13. Pruritic Papular Eruption
Shown here is the right leg of a 30 year old man, who presents with a severe pruritic rash involving both extremities and trunk for 7-8 months.
Courtesy of Charles Steinberg MD

14. Pruritic Papular Eruption
Another patient with a chronic itchy rash involving extremities and trunk, consistent with PPE.
Courtesy of Charles Steinberg MD

15. Apthous Ulcer
This is a 30year old man with HIV, CD4 100, presents with a painful lip ulcer for 2 weeks. The differential diagnosis includes syphilis, which usually presents as a painless lesion. Source:
Source: Copyright © David Reznik, D.D.S.

16. Herpes Zoster
25 year-old woman presents with a painful, vesicular rash (now crusted) involving left side of face, associated with left eye blurred vision. Source:
Courtesy of Tom Thacher, MD
Courtesy of the Public Health Image Library/CDC

17. Herpes Zoster
18 year old woman with hypopigmented scar involving left lower back, along a lumbar dermatome distribution. photo courtesy Samuel Anderson, MD
Courtesy of Samuel Anderson, MD

18. Molluscum Contagiosum
This 35 year-old man presented with asymptomatic papular lesions on his face. On close examination, these lesions have an“indented or scooped-out” center. photo courtesy Samuel Anderson MD
Molluscum contagiousum is caused by a pox virus and can be spread by skin-to-skin contact. They usually appear on the face and can be quite extensive in advanced immunosuppression. There are no systemic symptoms.
They can appear similar to cutaneous fungal infections, like cryptoccocus. However, the appearance of MC is differentiated by the presence of an umbilicated center and pearly white or skin colored appearance.
In contrast, the fungal infections are accompanied by systemic illness which may include pneumonia, meningitis and visual impairment. In cryptococcus the lesions may ulcerate and deposit an exudate that feels “gritty” when rubbed between the finger tips.

19. WHO Stage III
Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations
Severe weight loss (>10% of presumed or measured body weight)
Unexplained 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, empyema, pyomyositis, bone or joint infection, meningitis, bacteremia)
Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis
Both stage III and IV conditions are classified as either presumptive diagnoses or definitive (based on confirmatory testing).
Important to note that diarrhea and fever of Stage III must be unexplained (i.e. normal stool exam and appropriate work-up for fever).
Severe pneumonia might be defined by the presence of hypoxemia or associated organ failure, requiring of hospitalization.

20. WHO Stage III (2)
Conditions 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 month
These conditions are new additions to the WHO staging

21. Oral Candidiasis
This is a 22 year old woman with HIV, CD4 120, presenting with white lesion on the posterior tongue (and buccal mucosa - not shown).
This lesion could be scrapped off easily by tongue blade, supportive of candida.
Courtesy of Dr. R. Ojoh
Courtesy of Samuel Anderson, MD

22. Oral Candidiasis (2)
Need to question patients for symptoms of odynophagia (pain with swallowing) which might indicate candida esophagitis, a more advanced infection in HIV.
A more severe case of oral candidiasis with lip, tongue, palate involvement. Involvement at the commissures of the lips is called angular chelosis. This can be extremely painful and interfere with feeding. Another name for this fissure condition is “perleche.”
Source:

23. Oral Hairy leukoplakia
Lesions are typically thick and do not scrape off.
Need to have repeat evaluations as some early oral cancers can have a similar appearance.
This condition can be differentiated from oral candidiasis by the absence of pain or discomfort in the affected area of the tongue. On clinical exam you will see hair-like projections on the lateral margins of the tongue. These may be on one or both sides of the tongue and are white or gray/white in color and cannot be scraped off. The etiology is Epstein Barr Virus (EBV) and requires no treatment and in fact does not respond to antifungal therapy as used in candida. Improvement in appearance occurs with ARV treatment (or with Acyclovir if treatment is needed for cosmetic reasons).
Presence of OHL or oral candida in an HIV status unknown patient should prompt HIV counseling and testing.
Courtesy of Dr. R. Ojoh

24. Pyomyositis Large muscle groups, may be bilateral
Pathophysiology unclear
Tends to occur with advanced HIV infection
Diagnosis requires:
High index of suspicion
CT, 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
History of preceding local trauma described in 25% to 63% of cases of tropical pyomyositis

25. Pyomyositis
This patient presented with acute onset painful, swollen thigh muscle, associated with fever and nausea; photo courtesy Samuel Anderson MD
Courtesy of Samuel Anderson, MD

26. WHO Stage IV
Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations
HIV wasting syndrome
Pneumocystis pneumonia
Recurrent severe or radiological bacterial pneumonia
Chronic herpes simplex infection (orolabial, genital or anorectal of more than one month’s duration)
Oesophageal candidiasis
Extrapulmonary TB
Kaposi’s sarcoma
Central nervous system (CNS) toxoplasmosis
HIV encephalopathy
Note that bacterial pneumonia, when “recurrent severe or recurrent radiographic”, has been reclassified into a Stage IV condition.
While extrapulmonary TB (e.g. adenitis) is seen commonly in HIV-negative Ethiopians, it often reflects advance HIV disease in HIV-positive patients and is therefore considered a stage IV condition.

27. WHO Stage IV (2)
Conditions 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
Isosporiasis
Visceral herpes simplex infection

28. WHO Stage IV (3)
Conditions 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)
Recurrent non-typhoidal salmonella septicemia
Lymphoma (cerebral or B cell non-Hodgkin)
Invasive cervical carcinoma
Visceral leishmaniasis

29. Severe Chronic Herpes Simplex Ulcers
© Slice of Life and Suzanne S. Stensaas
Persistence for > 1 month is a stage IV-defining condition.
Chronic herpes simplex can be extremely painful and debilitating.
Lesions may involve not only the genital area but the mouth, lips, esophagus and skin.
Herpetic lesions can also become secondarily infected.
These lesions may be improved with ARV treatment, but chronic suppressive therapy with acyclovir is often required.

30. Disseminated Cutaneous Cryptococcosis
This 22 year old woman presented with extensive papular rash involving the face, associated with headache and confusion.
Lumbar puncture revealed fungal elements on india ink staining.
Courtesy of Samuel Anderson, MD

31. Disseminated cutaneous cryptococcosis (2)
Head ache had resolved and skin lesions show partial recession after 10 days of high dose oral fluconazole
Courtesy of Samuel Anderson, MD

32. HIV wasting syndrome Weight loss >10% body weight plus
Unexplained chronic diarrhea (>1 mo) or
Unexplained fever (>1 mo) plus chronic weakness
This diagnosis requires a combination of signs.

33. HIV encephalopathy (AIDS dementia complex)
Dementia - persistent cognitive decline with preserved alertness
Complex - concomitantly altered motor performance and, at times, behavior; myelopathy may be prominent
Disabling condition that interferes with activities of daily living
Progresses over weeks to months
Absence of concurrent illness or condition that could explain findings
Limited treatment options; ART may be helpful
This diagnosis requires a combination of both dementia and motor symptoms

34. Kaposi’s sarcoma Epidemiology Clinical manifestations
Human herpesvirus-8 (HHV-8) necessary but not sufficient for KS to develop
most common AIDS-associated neoplasm
increased frequency in all HIV transmission groups compared to the general population
Clinical manifestations
Variable, from an indolent process to a disseminated, aggressive disease
skin lesions
oral lesions
others sites
Clinical manifestations
Variable, from an indolent process to a disseminated, aggressive disease
skin lesions: painless pigmented macules, plaques, papules, or nodules; range in size from a few millimeters to large confluent areas
oral lesions: hard palate lesions are most common; seen also on gingiva, tongue, uvula, tonsils, pharynx;
others sites: lung, GI tract, liver, lymph nodes (lymphedema)

35. Kaposi’s Sarcoma: Management
ART: an essential component of KS management; lesions may regress
Local irradiation: bulky/obstructive lesions (e.g. oropharyngeal)
Systemic IFN-alfa: slow progressive disease
Systemic chemotherapy: rapid, life threatening disease including pulmonary or severe lymphedema

36. Kaposi’s Sarcoma
Dark asymptomatic macules and papules characterize Kaposi’s sarcoma.
This condition can create symptoms due to mass effect (eg orpharyngeal) and bleeding (GI or pulmonary)
source:
Courtesy of Tom Thacher, MD

37. Kaposi’s Sarcoma
This 32 year-old man presented with extensive dark macular lesions on face, trunk, and back.
His face was also very edematous, a consequence of extensive lymphatic obstruction, with significant resolution seen here after one month of ART.
Courtesy of Samuel Anderson, MD

38. Introductory Case: Lake (3)
The patient was counseled and started on NVP/3TC/d4T. At his 6 month f/u visit, he states that his symptoms have resolved and he has returned to work.
Examination reveals wt of 47kg and a persistent papular lesions with evidence of recent excoriations.
What additional information is necessary for current WHO staging of this patient?
The patient has responded clinically to ART.
The present findings are consistent with WHO stage II, based on the presence of minor cutaneous findings (PPE). However, further history should be obtained to characterize this rash - it may be drug reaction.

39. Introductory Case: Lake (4)
The patient returns again after 12 months of ART. He has developed head ache, anorexia, cough, and unilateral weakness.
What additional information is needed for current WHO staging of this patient?
New symptoms in a patient should prompt the physician to evaluate for treatment failure. The clinician needs to obtain a full history & physical examination, CD4 count, and CXR and sputum. Adherence to regimen must be assessed.

40. Introductory Case: Lake (5)
Wt is now 40kg
Thrush is present
Spastic left hemiparesis is confirmed
CXR normal
Sputum negative for AFB
Any additional information necessary for staging this patient?
Presence of unilateral hemiparesis is suggestive of toxoplasmosis, though CNS -pulmonary symptoms may be consistent with disseminated TB.
If available, a downward trend in CD4 count would be supportive of treatment failure.
In this patient resolution of headache and partial return of strength occurred after 5 days of anti-toxo treatment; the patient was re-staged WHO stage IV.

41. Case Studies
Step 3: Case Studies - Clinical Staging of HIV Patients (Slides 41 – 49) – 20 minutes

42. Case Study: Betrukan
Betrukan, 19, meets a man she likes very much who lives in the same town. Solomon, handsome, funny and a few years older, has his own butchery. Solomon is unaware that he has been living with HIV for 3 years. Solomon and Bertukan become a couple. They have unprotected sex as Bertukan, a secretary for a medical office, has been on OCPs (oral contraceptive pills) for a year.

43. Case Study: Betrukan (2)
Ten days later, Bertukan misses work due to a flu-like illness. She has fever, her joints ache and her glands are swollen.
2 months later, Bertukan decides to be tested for HIV, but Solomon declines. Bertukan feels well. Bertukan gets tested, and is seroreactive.

44. Case Study: Betrukan (3)
What are some reasons people might not get their test results?
What is Bertukan’s WHO classification?
What is Solomon’s WHO classification?
Answers:
Fear of finding out results, denial, other?
Stage I
Unknown, but suspect Stage I with information given.

45. Case Study: Betrukan (4)
Eighteen months later Bertukan and Solomon are expecting their first baby. Her antenatal clinic has been providing HIV information and PMTCT for some time. Group education regarding HIV and safe motherhood includes HIV testing as routine pre-natal care.
She discloses her status to Solomon who has not been feeling well – he has lost 4 kg in the past few weeks and has been having diarrhea. He agrees to HIV testing and his test is positive.

46. Case Study: Betrukan (5)
What WHO stage is Solomon now?
What should happen next at the clinic?
Answers:
Stage II vs III (diarrhea, wt. loss). Need to assess duration and cause of diarrhea. Also need to quantify % body wt loss.
Assess TLC or CD4 count. If CD4 <200, start co-trimoxazole preventive therapy (CPT). Evaluate and rule out active TB. Consider Solomon for ART. Note: HIV and pregnancy will be addressed in detail in a later Unit.

47. Case Study: Rahel
37yo Ethiopian woman presents w/1 yr history of oral candidiasis. HIV Elisa negative 1 yr ago. Repeat Elisa was positive and she is referred to your clinic.
PMH: non contributory
SH: lives alone, earns 500 birr/mo, no ETOH, has no current sex partner and no prior use of condoms or birth control
ROS: non-contributory.

48. Case Study: Rahel (2) Tearful woman T37, Wt 55kg,Ht 5’5”
HEENT: white plaques / pseudomembranes on posterior pharynx , no OHL, no adenopathy
Heart, Lungs, Abd: normal
Skin: seborrheic dermatitis of face
Pelvic: thick, white discharge, KOH+

49. Case Study: Rahel (3) What is her current WHO stage?
Is she a candidate for ART?
What are the immediate health care issues to be addressed at initial visit?
What other issues need to be addressed before ART is considered?
Current WHO Stage III (thrush)
Yes, she is eligible for ART
Candidiasis (OP and vaginal)
Financial, food, support system, assess for depression, adherence issues, condom use

50. Key Points
WHO 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 diagnosis, prior to starting ART, and with each follow-up visit to assess response to ART
Step 4: Summary of Key Points (Slide 50) – 5 minutes