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Prophylaxis of Opportunistic Infections

HAIVNHarvard Medical School AIDS

Initiative in Vietnam

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Learning Objectives

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

Differentiate between primary and secondary prophylaxis

Explain the benefits and indications of cotrimoxazole prophylaxis

Describe the process of cotrimoxazole desensitization

Describe how to provide isoniazid (INH) prophylaxis

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Relationship Between CD4 Count and Opportunistic Infections

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 the CD4 count determines the OIs a person is at risk for

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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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Two Types of OI Prophylaxis

Primary prophylaxis:

Giving medication to prevent an OI from occurring in the first place

Secondary prophylaxis:

Giving medication after an OI is treated to prevent it from recurring

Also known as maintenance therapy

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Cotrimoxazole Prophylaxis (CTP)

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Cotrimoxazole (1)

Can prevent: PCP Cerebral toxoplasmosis Malaria Parasitic diarrheas Non-typhoid salmonelloses Streptococcus pneumoniae

pneumonia

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Cotrimoxazole (2)

Benefits Decreases

morbidity and mortality

Inexpensive Well tolerated Prepares patient

for daily medication taking (adherence)

Concerns Hypersensitivity

(allergic) rash Anemia

The benefits greatly outweigh the risks

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Cotrimoxazole Allergy (1)

Clinically:• Maculopapular rash • Can have fever• Usually within first few weeks of

treatment Epidemiology• No studies in Asia• In Africa, about 2% had allergy to CTX*

Resolves when drug is stopped* Lancet. 2004 Oct 16-22;364(9443):1428-34.

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Cotrimoxazole Allergy (2) – How to Manage?

Grade Management I – II • Continue CTX

• Give antihistamines• Follow closely

III • Stop CTX• Consider desensitization or switch to

alternate prophylaxisIV • Stop and do not use CTX again

• Use alternate prophylaxis regimen with dapsone

Vietnam MOH guidelines on treatment of HIV/AIDS, 2009

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Cotrimoxazole Desensitization

Desensitization is a rechallenge following an adverse reaction starting with low doses and gradually escalating

Review patient daily or give instructions on how to respond to any reaction:

Type of reaction Action

No reaction • Progress to the next stage

Minor reaction • Continue same dose for 1 extra day or until the reaction subsides

• Once reaction subsides: progress to the next stage

Severe, worsening or persistent reaction

• Stop CTX

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When to Start CTP in Vietnam?

Indications:• CD4 ≤ 350 (any clinical stage)• WHO Stage 3 or 4 regardless of CD4 count• If CD4 testing is not available: clinical stage

2, 3, 4• Pregnant women can use CTX for entire

pregnancy Dose: • Adult: 960 mg/day or 960mg 3x /week• Pediatric: 5 mg/kg/day

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When to Stop CTP in Vietnam?

No ARV: continue lifelong

With ARV: stop cotrimoxazole when CD4 > 350

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What Should You Do When You Cannot Use

Cotrimoxazole?

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Dapsone

Indications: • Prophylaxis of PCP in patients with allergy

or adverse reaction to cotrimoxazole Dose:• Adults: 100 mg daily• Pediatrics: 2 mg/kg once a day

Note: not effective against other OIs Side effects (uncommon): rash,

haemolytic anemia, hepatitis

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TB Prophylaxis Therapy

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Isoniazid Preventive Therapy (IPT)

Indication: • PLHIV with negative TB screening

Dose: Isoniazid 300 mg (5 mg/kg) once daily for 9 months

Must exclude active TB

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Case Study: Duong

Duong, a 23-year-old man is newly diagnosed with HIV• He is clinical stage 1• His initial CD4 count returns at 89

cells/mm3

You perform a TB symptom screen:• He denies fever, cough, sweats, and weight

loss What OIs is he at risk for? What prophylaxis would you start?

Primary Prophylaxis for Select OIs

Disease/ Agent Indication Primary Prophylaxis

When to stop?

Pneumocystis jiroveci

CD4 < 200 or WHO Stage 3

or 4Cotrimoxazole (960mg tab) once daily

CD4 > 200 cells/ml for

more than 6 monthsToxoplasma

gondiiCD4 < 100 or WHO Stage 4

Mycobacterium tuberculosis

Negative TB screening

tests

INH 300 mg daily x 9 months

After treatment

course

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Secondary Prophylaxis

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Secondary Prophylaxis of OIs (1)

Also called “Maintenance Therapy” OI medication is continued to prevent

relapse Continued for life or until the patient:• starts ART• has an increase in CD4 count which

persists over a specified period of time

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Secondary Prophylaxis of OIs (2)

OIs which require secondary prophylaxis include:• PCP• Cerebral toxoplasmosis• Systemic fungal infections• Disseminated MAC infection• CMV disease

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Secondary Prophylaxis for Select OIs

Disease / Agent

Indication Secondary Prophylaxis

When to stop?

Pneumocystis jiroveci

Prior history of PCP

CTX (960mg) 1 tablet daily

CD4 > 200 cells/ml for more than 6

months

Toxoplasma gondii

Prior history of Toxoplasma encephalitis

Cryptococcus neoformans

Prior history of cryptococcosis

Fluconazole 150-200 mg/day

Penicillium marneffei

Prior history of penicilliosis

Itraconazole 200 mg daily

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Case Study: Nga

Nga, a 25-year-old woman, presents to your clinic for follow-up of penicillium infection• She is about to complete 10 weeks of intensive

phase treatment (Itraconazole 400 mg/day)• She has recently been started on ART• She is feeling well and wants to know whether

she can stop the Itraconazole at the end of the 10 week course

What should you recommend regarding the Itraconazole?

When can she safely stop it?

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Key Points

Many OIs can be prevented with the use of primary or secondary

CTP is inexpensive, effective against many OIs, and reduces overall morbidity and mortality

IPT can prevent latent TB from becoming active TB

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Thank you!

Questions?