Treatment and Prevention of Opportunistic Infections: Options for the Caribbean Region Jonathan E. Kaplan, M.D.

What is the most frequent serious opportunistic infection in HIV-infected adults in the Caribbean region? A.Pneumocystis jiroveci pneumonia (PCP) B.Toxoplasmic encephalitis C.Tuberculosis D.Cryptosporidiosis E.Hookworm infection

Do you have computerized tomography (CT) or magnetic resonance imaging (MRI) available to you in your practice setting? A.Yes, CT B. Yes, MRI C. Yes, both D. No, neither E. Don’t know what these techniques are

Do you have cryptococcal antigen (CRAG) testing available to you in your practice setting? A.Yes B.No C.I’ve never heard of this test

Can you diagnose Pneumocystis jiroveci pneumonia (PCP) in your practice setting? A.Yes B. No C. Don’t know

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 Complications CD4+ cell Count Asymptomatic HZV OHL OC PCP CMV, MAC TB TB Months Years After HIV Infection Acute HIV infectionsyndrome Relative level of Plasma HIV-RNA Relative level of Plasma HIV-RNA CD4+ T cells

Prevalence of AIDS-Defining Conditions among Persons with AIDS, Haiti (n=23) Prevalence Tuberculosis39% Wasting syndrome31% CD4 count <200 cells/uL10% Cryptosporidiosis 4% Cyclospora diarrhea 4% Cryptococcal meningitis 4% Candida esophagitis 4% Toxoplasmosis 4% Source: Deschamps, AIDS, 2000

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

AFB 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

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), 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)

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 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

Mucocutaneous 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)

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 Acute Care: syndromic treatment of illness - appropriate for all patients, but with attention to HIV; - oriented to Health Center level

Immune 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)

Annual Trends in the 15 Most Common Incident Opportunistic Illnesses, ASD Project, Incidence per 1000 person-years Pneumocystis jiroveci PneumoniaEsophageal Candidiasis Mycobacterium avium ComplexWasting Syndrome Kaposis SarcomaCytomegalovirus Retinitis Recurrent PneumoniaHIV Encephalopathy Cytomegalovirus DiseaseExtrapulmonary Cryptococcosis Pulmonary TuberculosisToxoplasmosis of Brain Chronic Herpes SimplexChronic Cryptosporidiosis Progressive Multifocal Leukoencephalopathy

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

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 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) 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 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 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