Transcript Session 14 - Teaching Slides

Starting ART in the Context
of Opportunistic Infections
HAIVN
Harvard Medical School
AIDS Initiative in Vietnam
1
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

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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
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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
General Principle: Treat the OI first
CD4 > 250
Treat the OI through the acute phase
before starting ARV
CD4 < 250
Start ARV as soon as possible, usually 2
weeks after starting treatment for OI
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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
• Start TB therapy first
CD4 > 350
• Assess for ART after intensive phase or after
completion of TB treatment*
• Start TB treatment first.
CD4: 250-350 • 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)15
Which ARV to Start?
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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)
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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)

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Tuan Anh is started on treatment for
cryptococcal meningitis
His treatment plan includes:
•
•
•
•
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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
Oral and esophageal
candidiasis
ARV can be started
after 2 weeks
ARV can be started as
soon as patient can
swallow pills
Non-systemic infections, e.g.: no contraindications
•Herpes zoster
to starting ARV early
•Herpes simplex
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•STDs
OI Drug Interactions (1)
Some OI drugs may have decreased blood levels
due to increased metabolism:
Effect on OI drug level when used with:
OI Drug
Rifampicin
EFV
NVP
Itraconazole,
Fluconazole,
Ketoconazole



Clarithromycin



Erythromycin

-
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OI Drug Interactions (2)
Some OI drugs may have decreased blood
levels due to decreased absorption:
OI Drug
Effect on OI drug absorption when
used with:
DDI
H2 Blockers
PPI
Itraconazole,
Ketoconazole



Fluconazole
-
-
-
Fluoroquinolones

-
-
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Case Study, Phuong (1)
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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)
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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
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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?
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