Treatment and Prevention of Opportunistic Infections:Options for the Caribbean

Region

Treatment and Prevention of Opportunistic Infections:Options for the Caribbean

Region

Excerpted from presentation by Jonathan E. Kaplan, M.D.

Excerpted from presentation by Jonathan E. Kaplan, M.D.

What is the most frequent serious opportunistic infection in HIV-infected adults in the Caribbean region?

A. .Toxoplasma gondii encephalitis

B. .Tuberculosis

C. .Pneumocystis jiroveci pneumonia (PCP)

D. .Cryptosporidium spp. infection

E. .Hookworm infection

Can you confirm the diagnosis of Pneumocystis jiroveci pneumonia (PCP) in your practice setting?

A. Yes

B. No

C. Don’t know

What clinical specimens are collected to diagnose Pneumocysis infection? • Expectorated sputum

• Induced sputum

• Bronchial washings

• Lung biopsy

• Blood cultures

How you confirm cryptococcal infection in your practice setting?

A. India Ink stain

B. Culture

C. Cryptococcal antigen test

Chemoprophylaxis against Pneumocystis jiroveci pneumonia (PCP) with trimethoprim-sulfamethoxazole (TMP-SMZ) can also reduce the incidence of:

A. Non-typhoidal Salmonella disease

B. Toxoplasmic encephalitis

C. Bacterial pneumonia

D. Isosporiasis

E. All of the above

Natural Course of HIV Infection and Common ComplicationsNatural Course of HIV Infection and Common Complications

00

100100

200200

300300

400400

500500

600600

700700

800800

900900

10001000

0 1 2 3 4 5 1 2 3 4 5 6 7 8 9 10 110 1 2 3 4 5 1 2 3 4 5 6 7 8 9 10 11

CD

4+ c

ell C

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nt

CD

4+ c

ell C

ou

nt

AsymptomaticAsymptomatic

HZVHZV

OHLOHL

OCOCPCPPCP

CMV, MACCMV, MACTBTB

TBTB

MonthsMonths Years After HIV InfectionYears After HIV Infection

Acute HIVAcute HIVinfectioninfectionsyndromesyndrome

Relative level of Plasma HIV-RNARelative level of Plasma HIV-RNA

CD4+ T cellsCD4+ T cells

Caribbean Guidelines for the Treatment of Opportunistic Infections in Adults and Adolescents Infected with the Human Immunodeficiency Virus

Mucocutaneous Candidiasis: TreatmentMucocutaneous Candidiasis: Treatment

• Oral candidiasis (thrush)

• Esophageal candidiasis

Clotrimazole troches, 10 mg 5 times/day for 7 days

Fluconazole, 3-6 mg/kg/day for 1-2 weeks. Chronic maintenance therapy suggested for several months (fluconazole, 200 mg/day)

Pneumocystis jiroveci (formerly carinii) Pneumonia (PCP)Pneumocystis jiroveci (formerly carinii) Pneumonia (PCP)

• History: subacute onset (days to weeks) of shortness of breath, dry cough, fever

• Physical exam: tachypnea and hypoxemia• CXR typically shows bilateral, diffuse,

interstitial pulmonary infiltrates• Diagnosis difficult: requires bronchoscopy or

sputum induction and special stains• Treatment: TMP-SMZ (cotrimoxazole, CTX),

15-20 mg/kg/day for 3-4 weeks• For severe cases, add prednisone, 40 mg/day

tapering over 3 weeks• Chronic maintenance therapy required (CTX

160/800 mg/day)

AFB SmearAFB Smear

AFB (shown in red) are tubercle bacilli

Tuberculosis in HIV-Infected Persons

• Causes 11% of HIV-related deaths worldwide• Can occur at any CD4 count• Clinical presentation increasingly atypical as

CD4 count declines• In resource-poor areas, a significant percentage

of newly-diagnosed HIV-infected persons will be found to have active TB

• Should always consider TB in an HIV-infected persons with a pulmonary infiltrate

Bacterial Pneumonia in HIV-Infected Persons• About 8 times more common in HIV-infected

vs non-HIV-infected persons• Pneumococcal bacteremia about 100 times

more common• Can occur at any CD4 count• Common etiologies: S. pneumoniae, H.

influenzae, P. aeruginosa, S. aureus• Treatment: penicillin/ampicillin +/-

aminoglycoside; or cephalosporin

Cryptococcal Meningitis

• History: severe headache, fever, mental disturbance

• Physical exam: no focal neurological signs• Differential: bacterial, TB• LP: high opening pressure, elevated protein,

low glucose, organisms• Treatment: amphotericin x 2 wks, then

fluconazole x 8-10 weeks• Chronic maintenance therapy: fluconazole,

200mg/day

Cerebral toxoplasmosisCerebral toxoplasmosis• History: headache, fever, confusion, motor

weakness

• Physical exam: focal neurological signs

• Diagnosis: demonstration of multiple mass lesions on CT or MRI

• Treatment: pyrimethamine plus sulfadiazine plus folinic acid for 8 weeks

• Chronic maintenance therapy: same

WHO Integrated Management of Adolescent and Adult Illness

• Consists of 4 modules: Acute Care, Chronic HIV Care with ARV Treatment, General Principles of Good Chronic Care, Palliative Care

• Posted on WHO website in Dec 2003 (available at www.who.int/3by5/publications/imai/en/)

• Acute Care: syndromic treatment of illness

- appropriate for all patients, but with attention to

HIV;

- oriented to Health Center level

Immune Reconstitution SyndromesImmune Reconstitution Syndromes

• Tuberculosis (“paradoxical reaction”)

• Mycobacterium avium complex (MAC)

• Pneumocystis jiroveci pneumonia (PCP)

• Toxoplasmosis

• Hepatitis B

• Hepatitis C

• Cytomegalovirus (CMV)

• Varicella Zoster Virus (VZV)

• Cryptococcosis

• Progressive multifocal leukoencephalopathy (PML)

Caribbean Guidelines for the Prevention of Opportunistic Infections in Adults and Children Infected with Human Immunodeficiency Virus

What diseases may be prevented?What diseases may be prevented?

• Pneumocystis jiroveci pneumonia (PCP)

• Cerebral toxoplasmosis

• Tuberculosis

• Mycobacterium avium complex (MAC) disease

• Disease caused by S. pneumoniae

Prophylaxis against PCP

• Survival benefit demonstrated; first recommended in 1989

• Eligibility criteria: CD4 count <200 cells/uL or <14% or history of oral candidiasis

• Drug of choice: TMP-SMZ (CTX) 160/800 (1 double-strength tab) qd

Cotrimoxazole ProphylaxisCotrimoxazole Prophylaxis

Can prevent:

• Pneumocystis jiroveci pneumonia• Cerebral toxoplasmosis• Disease caused by S. pneumoniae• Disease caused by non-typhoid Salmonella• Nocardiosis• Isosporiasis• Malaria

CTX Prophylaxis: Other Advantages

• Cheap ($1 US/month)• Easy to administer: only contraindication is

history of sulfa allergy• Main adverse reaction is skin rash, but

uncommon in dark-skinned persons• Clinical monitoring is adequate• Adherence is not critical• Experience taking daily medication; good

preparation for ART

Isoniazid Preventive Therapy (IPT)Isoniazid Preventive Therapy (IPT)

• International “best practice”• If skin testing available, may reserve for persons with

positive tuberculin skin test (> 5 mm induration)• Otherwise, IPT suggested for all HIV-positive patients

living in countries with high prevalence of TB• IPT also suggested for HIV-positive persons exposed

to case of active TB• Give isoniazid (INH), 300 mg per day for 9 mo• EXCLUSION OF ACTIVE TB IS CRITICAL

Preventing Disease Recurrence: OIs that Require Preventive Therapy for LifePreventing Disease Recurrence: OIs that Require Preventive Therapy for Life

• PCP

• Cerebral toxoplasmosis

• Systemic (deep) fungal infections: cryptococcosis, histoplasmosis

• Disseminated MAC infection

• CMV disease

Prophylaxis against First Episode of Opportunistic Disease in HIV-exposed/infected Infants and Children

Prophylaxis against First Episode of Opportunistic Disease in HIV-exposed/infected Infants and Children

Pathogen

Pneumocystis jiroveci

Mycobacterium tuberculosis

Indication

HIV-exposed/infected children 1-12 months; older HIV-infected children with CD4< 15%

Contact with person with TB

Drug

Cotrimoxazole

Isoniazid