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Overview of Opportunistic Infections

in HIV/AIDS

HAIVNHarvard Medical School AIDS

Initiative in Vietnam

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Learning Objectives

By the end of this session, participants should be able to:

Explain the relationship between CD4 count and incidence of specific opportunistic infections (OIs)

Describe the most common OIs in Vietnam including:• clinical presentation• diagnosis • national treatment recommendations

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What is an Opportunistic Infection (OI)?

An infection caused by pathogens that usually do not cause disease in a host with a healthy immune system

A compromised immune system presents an "opportunity" for the pathogen to infect

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What is the Relationship Between CD4 Count and OIs?

The lower a person’s CD4 count is, the more vulnerable he/she is to opportunistic infections (OIs)

Different infections can occur based on how weak a person’s immune system is

The level of CD4 count determines the OIs for which a person is at risk

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Sample OIs per CD4 Count

CD4 Count OI / Condition> 500/mm3 Candidal vaginitis

Persistent generalized lymphadenopathy

200-500/mm3 Pneuomoccal pneumoniaPulmonary tuberculosisHerpes zosterOropharyngeal candidiasis (Thrush)

< 200/mm3 Pneumocystis jiroveci pneumoniaMiliary/extrapulmonary TB

< 100/mm3 Candida Esophagitis PenicilliosisToxoplasmosisCryptococcosis

< 50/mm3 Mycobacterium avium complex (MAC)Disseminated cytomegalovirus (CMV)

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Key Principles of OI Diagnosis and Treatment

Accurate diagnose of OIs require consideration of: • Clinical features• Severity of immunosuppression• Results of specific lab tests

Patients often have multiple OIs at the same time

Drug-drug interactions are an important consideration in the management of OIs

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Clinical Presentation, Diagnosis

and Treatment of Major OIsin Vietnam

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What are Common OIs in Vietnam?

Oral Candidiasis (Thrush)

Tuberculosis Penicilliosis Cryptococcal

Meningitis PCP Cerebral

Toxoplasmosis

Cytomegalovirus (CMV) Retinitis

Mycobacterium Avium Complex (MAC)

Cryptosporidiosis Isosporiasis and

Cyclosporiasis

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Oral Candidiasis (Thrush)

Most patients have no symptoms

Shows as white plaques on palate, gums

Treatment:1. Fluconazole

150mg/day for 7 days

2. Ketoconazole 200mg bid for 7 days

White plaques on palates, removable by tongue blades

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Candida Esophagitis

Patients complain of: pain in throat or

chest when swallowing

food getting “stuck” Treatment

Flu 200mg/day for 14 days

Itra 400 mg/day for 14 days

Keto 200 mg bid for 14 days

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Tuberculosis (1)

TB is the most common OI in Vietnam and the most common cause of death among HIV patients

Clinical symptoms of pulmonary TB include fever, cough, night sweats, weight loss, and bloody sputum

Extrapulmonary TB is more common in HIV+ compared to HIV- patients

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Tuberculosis (2)

Diagnosis: Clinical symptoms CXR Sputum AFB

smear Bronchoscopy

where available Tissue biopsy

(lymph nodes)

Right upper lobe infiltrate

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Pneumocystis jiroveci Pneumonia (PCP) (1)

Clinical manifestations include:• gradual onset of shortness of breath• dry cough• fever

Lung sounds may be clear or have faint crackles

Hypoxia is common Elevation of LDH is common but

nonspecific CD4 <200 (though occasionally higher)

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Pneumocystis jiroveci Pneumonia (PCP) (2)

Typical CXR • bilateral diffuse

infiltrations Atypical CXR

• normal result• blebs and cysts• lobar infiltrates

Suggestive CXR• pneumothorax

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PCP Diagnosis (1)

Diagnosis can be made clinically

Empiric treatment should be started if the diagnosis is suspected

Definitive diagnosis is made by sputum smear and stain Fluorescent stain

PCP Treatment

Condition, Medication

Treatment regimen

Trimethoprim-sulfamethoxazole (Cotrimoxazole)

• 15-20 mg/kg/day (of TMP) for 3 weeks

For severe cases, add prednisone (for 21 days)

• 40 mg twice daily for 5 days, then:• 40 mg daily for 5 days then: • 20 mg/day for 11 days

Then, chronic suppressive therapy: Cotrimoxazole

• 160/800 mg daily• Discontinue when CD4 >200 for 6

months on ARV

National Treatment Protocol

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Case Study: Duc (1)

Duc, a 30 year-old HIV positive man, presents to OPC with cough of 3 weeks duration• Scanty whitish sputum • Low grade fever• Developed shortness of breath one week ago• On examination he was in respiratory distress

with RR of 40/min and cyanosis What are the likely causes? What important tests would you request?

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Case Study: Duc (2)

Results of tests:

Sputum AFB: negative 3 times

CXR: bilateral infiltrates

CD4: 110/mm3

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Penicilliosis (1)

Causative agent Penicillium marneffei• First isolated in 1956 in Vietnam from the

bamboo rat Endemic in southeast Asia and

southern China First case reported in an AIDS patient

was in Vietnam in 1996 Majority of cases occur in patients

with CD4 cell counts < 100Source: Hien TV et al. CID 2001;32:e78-80.

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Penicilliosis (2)

Most common signs and/or symptoms include:• Fever• Weight loss• Skin lesions• Lymphadenopathy• Hepatomegaly• Splenomegaly• Anemia• Elevated AST, ALT

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Typical Skin Lesions of P. MarneffeiCutaneous papules with central necrotic umbilication.

May be confused with molluscum contagiosum or disseminated cryptoccocus.

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Penicilliosis - Diagnosis

P. marneffei cultures (blood or skin lesions) produce a distinct red diffusible pigment

Culture

Wright stain of skin lesions

Direct microbiological

exam

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Penicilliosis - Treatment

National Treatment Protocol

Condition Treatment RegimenSevere cases •Amphotericin B 0.7mg/kg/day IV for 2

weeks•Then itraconazole 200mg 2x/day for

next 8-10 weeks

Mild to moderate cases

• Itraconazole 200mg 2x/day x 8 weeks

Maintenance therapy

• Itraconazole 200 mg/day•Discontinue when patient is on ART

and has CD4 count > 200 cells/mm3 ≥ 6 months

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Cryptococcal Meningitis (1)

Clinical manifestations: Headache, fever, nuchal rigidity,

fatigue, mental disorders Course can be chronic (months) Meningeal signs may be absent in

advanced AIDS cases CD4<100

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Cryptococcal Meningitis (2)

Diagnosis of CM is done by examining cerebral spinal fluid (CSF) after performing a lumbar puncture• Opening pressure• CSF parameters (cell count, protein,

glucose)• Microbiology

India Ink stain Cryptococcal antigen test CSF culture

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Cryptococcal Meningitis - Treatment

Condition Treatment RegimenPreferred regimen

•Amphotericin B 0.7mg/kg/day IV for 2 weeks

•Then Fluconazole 800- 900 mg/day for next 8 weeks.

Mild cases or if amphotericin not available

•Fluconazole 800-900 mg/day for 8 weeks

Maintenance therapy

•Fluconazole 150-200 mg/day•Discontinue when patient is on ART

and has CD4 count > 200 cells/mm3 ≥ 6 months

*With management of elevated intracranial pressure

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Cerebral Toxoplasmosis

Seen in patients with CD4<100 Clinical manifestations:

• Fever• Headache• Confusion• Motor weakness• Focal neurological deficit• Seizures, stupor, coma

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Cerebral Toxoplasmosis – Diagnosis (1)

MRI of cerebral toxoplasmosis showing 2 ring enhancing lesions – “lighting up” with intravenous contrast

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Cerebral Toxoplasmosis – Diagnosis (2)

Empiric treatment with good clinical response• (+/-) improvement of brain imaging

Positive blood serology (IgG) to T. gondii• Indicates prior infection• Negative serology makes cerebral

toxoplasmosis less likely Brain or tissue biopsy

• crescent/banana shaped tachyzoites

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Cerebral Toxoplasmosis: Treatment

Treatment Type

Medication Regimen

Acute Treatment

Cotrimoxazole: TMP 10 mg/kg/day intravenously or orally for 3-6 weeks

OR:

Pyrimethamine: 200 mg loading dose, then 50-75 mg once daily

+ Sulfadiazine: 2-4g/initial dose, then 1- 1.5 g every 6 hours for 3-6 weeks

Maintenance Therapy

Pyrimethamine: 25-50 mg/day+ Sulfadiazine: 1g x every 6 hoursOR:Cotrimoxazole 960 mg (SMX 800mg / TMP 160mg) orally once per day Discontinue when patient is on ART with CD4 count > 100 cells/mm3 ≥ 6 months

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Case Study: Huong

Huong, a 31 year-old HIV-positive woman from Hanoi, presents with weakness of left upper and lower extremities for 5 days duration• Complains of fever, severe headache and

vomiting for last 2 weeks• Not taking any medication• Examination revealed a confused woman

with weakness of left extremities but no meningeal signs

What is Huong’s differential diagnosis?

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Mycobacterium Avium Complex (MAC)

Prevalence unknown in Vietnam • 3% of cohort of AIDS

patients in Hanoi Manifestations

• CD4 < 50 • Fever• Weight loss• Lymphadenopathy• Hepatosplenomegaly• Anemia

Diagnosis• Blood culture• Bone marrow and

lymph node biopsies with culture

Treatment• Clarithromycin or

azithromycin PLUS ethambutol

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Cytomegalovirus (CMV) Retinitis

Presentation: CD4 < 50 blurred vision blind spots “floaters” blindness painless condition Treatment: Ganciclovir

intravitreal* or intravenous injections

ART

* Ganciclovir intravitreal injections are available at the national level in both north and south Vietnam

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Cryptosporidiosis (1)

Caused by infection with C. parvum • generally infects small bowel mucosa

Transmission• ingestion of the cysts (usually in water

contaminated with feces) Can affect patients at any CD4 count

• CD4 < 100 are at highest risk for most severe infection

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Cryptosporidiosis (2)

Clinical presentationacute or subacutenon-bloody, watery diarrheanausea and/or vomitinglower abdominal crampsfever can occur

DiagnosisModified AFB stain

TreatmentSupportive ART to raise CD4 count

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Isosporiasis and Cyclosporiasis

Transmitted by ingestion of contaminated food and water

Clinical presentation• chronic voluminous watery diarrhea • abdominal cramps, nausea/vomiting• weight loss

Treatment• TMP-SMX 2 DS tablets twice or three times

daily for 2 – 4 weeks• ART to raise CD4 counts

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Case Study

A 32-year-old IDU comes to the clinic complaining of persistent diarrhea that started five months earlier

You do a CD4 count and stool exam• His CD4=70• His stool reveals cryptosporidium

How would you classify his clinical stage?

With a CD4 count of 70, what other OIs is he at risk for?

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Key Points

An OI is caused by pathogens that usually do not cause disease in a healthy host

Knowing a PLHIV’s CD4 count can help clinician better diagnose an OI

Accurate diagnose of OIs require consideration of: • Clinical features• Severity of immunosuppression• Results of specific lab tests

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Thank you!

Questions?