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Starting ART in the Context 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:

Explain the best time and clinical conditions that an acute OI patient can start ART

Describe how to start ART in the context of acute OIs

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Starting ARV in the Context of OIs:Advantages and Disadvantages

Advantages Recovery of

immune system Mortality reduction Treatment of OI Prevention of other

OI and complications due to HIV disease

Disadvantages Risk of IRIS Drug interactions Drug adverse

effects Number of pills:

adherence

It’s never an emergency to start ART

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General Principles (1)

Little data exist on best time to start ART when a patient is being treated for an OI• Clinical judgment must be used

Before starting ARV, patient should be:• Responding to OI therapy, clinically

stable • Tolerating OI drugs with no side effects

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General Principles (2)

It’s important to know drug-drug interactions of all medications before they are prescribed

If the patient is already on ART, do not stop • Continue ART and start OI treatment

• Change ART regimen if necessary to avoid interactions with OI drugs

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With Which OIs do you Need to Start ARVs Right

Away?

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OIs that Require ARVs to Resolve

Diarrheal agents Kaposi Sarcoma Progressive Multifocal

Leukoencephalopathy (PML) Non-infectious causes:

• Malignancy• Autoimmune conditions• Skin conditions

In these cases, ARVs should be started as soon as possible

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With Which OIs Should You Delay the Start of

ART?

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OIs With Which ART Should Be Delayed

Tuberculosis and other mycobacterial infections

Cerebral toxoplasmosis Pneumocystis Jiroveci Pneumonia

(PCP) Cryptococcosis Penicillium marneffei Other fungal infections

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Starting ARVs in the Context of an Acute OI

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Principles for Starting ARVs in the Context of an Acute OI

CD4 > 250Treat the OI through the acute phase before starting ARV

CD4 < 250Start ARV as soon as possible, usually 2 weeks after starting treatment for OI

General Principle: Treat the OI first

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ART and Tuberculosis

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Antiretroviral Therapy and TB: Early vs. Late ARV (1)

TB is associated with increased HIV disease progression

Benefits of early ARV:• Reduction in HIV viral load and slowing

of HIV disease progression• Reduction in risk of developing other OIs• Prevention of new AIDS defining

illnesses and reduction in mortality

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Antiretroviral Therapy and TB: Early vs. Late ARV (2)

However, there are also risks to starting ARVs early such as:• Drug toxicity/intolerance

hepatotoxicity peripheral neuropathy from INH & D4T drug allergy or hypersensitivity

• Drug interactions (RIF & ARV)• Pill burden (>15 pills/day)• IRIS • Patient may be ready for ARV or not

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HIV and TB: When to Start ARVs?

If CD4 Available

CD4 > 350• Start TB therapy first• Assess for ART after intensive phase or after

completion of TB treatment*

CD4: 250-350• Start TB treatment first. • Start ARV after intensive phase (2 months) of

TB treatment*

CD4 < 250• Start TB treatment then start ARV as soon as

TB treatment is tolerated (2-8 weeks)

Guidelines for Diagnosis and Treatment of HIV/AIDS, MOH Vietnam. 2009.

* If patient is at clinical stage 4, provide ART immediately after the tolerance of TB drugs (between 2-8 weeks)

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Which ARV to Start?

If patient is already on ART, do not stop If patient is on RIF and EFV is available,

substitute EFV for NVP If EFV is not available or if patient cannot

take EFV, then:• Use NVP with TB treatment

Second Line ARV:• Cannot take PI with RIF due to PI drug

levels• Refer to specialty center for treatment

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Case Study, Lan (1)

Lan, a 29 year old woman is referred to the HIV OPC by the district TB center• Just diagnosed with pulmonary TB and also

had a positive HIV test.• Has been taking TB drugs (RHEZ) for 2

weeks• TB doctor has referred her to your OPC for

ART What factors should you consider when

deciding when to start ART for this patient?

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Case Study, Lan (2)

Further information:• The CD4 cell count is 25 cells/mm3. • Other lab tests are within normal limits• She has been tolerating the TB drugs

without difficulty and with good adherence.• She lives close by and is willing to return to

the OPC frequently for close monitoring When would you recommend she start

ART? What ART regimen would you

recommend?

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ART and Cryptococcus Meningitis

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Timing of ART in Cryptococcal Meningitis (CM) (1)

Optimal time to start ART in patients with CM is not clear• There are conflicting data from studies

examining the risk of mortality from IRIS associated with a diagnosis of CM

• Increased intracranial pressure related to IRIS may result in higher rates of morbidity and mortality

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Timing of ART in Cryptococcal Meningitis (2)

General Recommendations Defer starting ART until patients are

clinically stable on anti-fungal treatment

Usually occurs between 2-10 weeks after starting cryptococcal treatment

Regardless of when starting ART, aggressive management of elevated intracranial pressure is vital

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Case Study, Tuan Anh (1)

Tuan Anh, a 30 year old man with HIV presents to the hospital because of 4 days of fever, severe headache, and blurry vision.

His CD4 count is 70. A lumbar puncture is performed.

• WBC count 20 cells/cc3, with 90% lymphocytes. • Protein 0,85g/l• Glucose normal• India Ink stain is positive for many Cryptococcus yeast forms.

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Case Study, Tuan Anh (2)

Tuan Anh is started on treatment for cryptococcal meningitis

His treatment plan includes:• Management of intracranial pressure• Amphotericin B at 0.7mg/kg/day for 2 weeks • Fluconazole 900 mg/day for another 8 weeks • Secondary prophylaxis with fluconazole 150

mg/day At which point during this treatment course

would you start ARV?

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ART in the Context of Other Acute OIs

Type of Condition Action

Severe infections, e.g.:•PCP•Penicillium•Bacterial infections

ARV can be started after 2 weeks

Oral and esophageal candidiasis

ARV can be started as soon as patient can swallow pills

Non-systemic infections, e.g.:•Herpes zoster•Herpes simplex•STDs

no contraindications to starting ARV early

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OI Drug Interactions (1)

OI DrugEffect on OI drug level when used with:

Rifampicin EFV NVP

Itraconazole, Fluconazole, Ketoconazole

Clarithromycin

Erythromycin - -

Some OI drugs may have decreased blood levels due to increased metabolism:

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OI Drug Interactions (2)

OI Drug

Effect on OI drug absorption when used with:

DDI H2 Blockers PPI

Itraconazole, Ketoconazole

Fluconazole - - -

Fluoroquinolones - -

Some OI drugs may have decreased blood levels due to decreased absorption:

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Case Study, Phuong (1)

Phuong, a 25 year old woman with HIV comes to the OPC with recurrent fever and skin lesions

2 months ago she was diagnosed with penicilliosis

She improved quickly after treatment with Itraconazole 200 mg twice daily

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Case Study, Phuong (2)

Now, however, symptoms have returned 4 weeks ago she started on ART (D4T, 3TC,

NVP) 2 weeks ago she decreased her

Itraconazole dose to 200 mg daily for maintenance therapy

What are possible explanations for Phuong’s recurrent penicilliosis symptoms?

How might you manage this situation?

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Key Points

For patient with an acute OI, start ART when patient is clinically stable and tolerating OI treatment

Patients with more advanced immunosuppression (CD4<250) should be started on ART as soon as possible (between 2-8 weeks)

Clinicians should be aware of potential interactions between OI drugs and ARV

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Thank You

Questions?