Transcript Session 8 - Teaching Slides

Starting ART in the
setting of Opportunistic
Infections in children
HAIVN
Harvard Medical School
AIDS Initiative in Vietnam
1
Learning Objectives
At the end of this presentation, each trainee
should be able to:
• Cite 3 opportunistic infections where ART is part of
the treatment
• Cite 4 opportunistic infections where ART initiation
may lead to IRIS
• Cite the recommendation of the MOH of the use of
NVP with a rifampicin (RIF) containing TB therapy
• Cite the best time and clinical conditions that a
patient with an acute OI can be started on ART
• List drug interactions between antifungal drugs and at
least 4 other drugs commonly used for HIV patients.
2
Outline of Presentation
• Introduction
• Interactions between OI and ART
– OIs for which ART facilitates their management
– OIs that may require delay of ARV
• When to start ARV after an OI
• Tuberculosis
– When to start ARV
– ARV regimens
• Interactions between OI medications and
other drugs commonly used in HIV patients
3
Starting ART in the setting of an
active Opportunistic Infection
Introduction
4
Starting ART and OIs:
Advantages and Disadvantages
• Advantages
–
–
–
–
Recovery of immune system
Mortality reduction
Facilitate OI management
Prevention of other OIs and
complications due to HIV
disease
• Disadvantages
–
–
–
–
Risk of IRIS
Drug interactions
Drug adverse effects
Number of pills:
adherence
Remember: it’s never an emergency to start ARV
(though one shouldn’t wait too long if pt has low reserve and CD4 count)
5
General Principles
• Specific data are limited to guide for:
– when to start ART in children with an acute OI
– how to manage ART when an acute OI occurs in a
child already receiving ART
6
General Principles
When to start ART in children with an
acute OI
• The decision of when to start ART in a
child with an acute or latent OI
– needs to be individualized
– vary by the degree of immunologic
suppression in the child prior to ART
• Check to ensure the child
– Is responding to OI therapy, clinically stable,
– Is tolerating the OI drugs with no side effects
(eg. rash)
7
General Principles
How to manage ART when an acute OI
occurs in a child already receiving ART
• In a child already receiving ART who develops an
OI, management will need to account for:
– the child’s clinical, viral, and immune status on ART
– the potential drug-drug interactions between ARVs and
the required OI drug regimen
• If the patient is already on ARV, then do not stop
– Continue the ARV and start treatment for the OI.
– Change ARV if necessary to avoid interactions with the OI
drugs.
8
In the setting of which OIs can you start
ARVs right away?
OIs that require immune restoration to
resolve
9
OIs that require ARV as part of
their treatment
•
•
•
•
Diarrheal agents: Cryptosporidiosis, Microsporidiosis
Kaposi’s Sarcoma
Progressive Multifocal Leucoencephalopathy (PML)
Non-infectious causes such as:
– malignancy (lymphoma, carcinoma)
– autoimmune (atopic dermatitis, psoriasis)
– skin (pruritic papular eruption, eosinophillic folliculitis,
seborrheic dermatitis)
In these cases, ART should be started as soon as possible
10
In the setting of which OIs
should ARV be delayed?
OIs that are likely to cause
immune recovery inflammatory
syndrome (IRIS), or whose
treatments have complicated drug
interactions with ARVs
11
OIs for which ART should be delayed
• Tuberculosis and other atypical
mycobacterial infections
• Cerebral toxoplasmosis
• Pneumocystis jiroveci Pneumonia (PCP)
• Cryptococcosis
• Penicillium marneffei
12
Starting ART in the presence of
an acute OI
General Principles:
• Treat the OI first: the patient should be
responding to treatment with improvement in
OI symptoms and tolerating the OI drugs.
• If the CD4 is high (> “severe” level), treat the
OI through the acute phase before starting
ARV
• If the CD4 is low (< “severe” level), the patient
is at risk for other OIs or death and should start
ARV as soon as possible, usually about 2
weeks after starting treatment for the OI
13
Early ART Reduces AIDS Progression/
Death in Individuals with Acute OIs
• Zolopa et al. PLoS ONE May 2009 | Volume 4 |
Issue 5 | e5575
• Randomized study of early (< 14 days) versus
deferred (> 28 days) ART in patients with acute
OIs or serious bacterial infections (BIs).
• 282 patients enrolled:
– Patients with TB excluded.
– Median CD4 = 29 cells/mm3, VL 5.07 log
– Early ARV: median 12 days
– Late ARV: median 45 days
14
Early vs. late ART in patients with OI
# (%)
PCP
177 (63%)
BI
34 (12%)
Cryptococcus
35 (12%)
Toxoplasmosis
13 (5%)
Histoplasmosis
10 (4%)
CMV
6 (2%)
MAC
6 (2%)
Multiple OIs/BIs 92 (33%)
• Majority of patients
had PCP
• Some cases of
bacterial infection
and cryptococcal
disease
• Patients with TB
were excluded
15
Early vs. late ART in patients with OI
Outcome
Early
ARV
Late
ARV
p
14%
24%
0.035
4.2
11.8
Undetectable VL at 48 wks
48%
45%
NS
IRIS
5.7%
8.5%
NS
Death or disease
progression
Weeks to CD4 > 100
Conclusion: Early ARV after OI diagnosis decreases risk of
death or disease progression in the first year of treatment.
16
Starting ARVs in the setting of an
active Opportunistic Infection
Tuberculosis
When should we start ARV?
What ARV should we start?
17
Antiretroviral Therapy and TB:
Early vs. Late ART
Benefits of early ART:
 TB is associated with
increased HIV disease
progression
 Reduced HIV RNA levels
and slow HIV disease
progression.
 Reduced risk of
developing other
opportunistic infections
 For patients with
CD4<200, early ARV
prevents new AIDS
defining illness and
reduces mortality
Risks of Early ART:
 Drug toxicity/intolerance
(hepatotoxicity, peripheral
neuropathy from INH &
D4T, drug
hypersensitivity)
 Drug interactions (RIF &
ARV)
 Pill burden (>15 pills/day)
 IRIS
 Patient may or may not
be ready for ARV
18
HIV and TB: When to start ART
If CD4 counts are 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 weeks-8 week)
* If the patient is at clinical stage 4, provide ART immediately
after his/her tolerance of TB drugs (between 2 and 8 weeks).
Guidelines for Diagnosis and Treatment of HIV/AIDS, Ministry of Health, Vietnam. 2009. 19
What ARVs to start?
• If the child is on ART already, do not stop
• If the TB regimen contains RIF and the child is on:
– Non-NVP/LPV/r regimen, continue the ART regimen
– NVP regimen:
• The child < 3 years or < 10 kg of BW: substitute
ABC for NVP
• The child > 3 years and > 10 kg of BW: substitute
EFV for NVP
• ABC and EFV not available: continue NVP
– LPV/r regimen: add more ritonavir
• Ratio 1 LPV: 1 ritonavir
20
What ARVs to start?
• If the child is on TB regimen with RIF and starts
ART:
– The child < 3 years or < 10 kg of BW:
• AZT/d4T + 3TC + ABC
• ABC not available: AZT + 3TC + NVP
– The child > 3 years and > 10 kg of BW:
AZT/d4T + 3TC + EFV
21
ARV for other acute OIs
• For severe infections such as PCP,
penicillium, bacterial infections: ARV can be
started after 2 weeks if the patient is
responding to the OI treatment and is
clinically stable
• For oral and esophageal candidiasis, ARV
can be started as soon as patient can
swallow pills
• For non-systemic infections such as herpes
zoster, herpes simplex, STDs, there are no
contraindications to starting ARV early
22
Case study
• A 4 month infant was brought by her
mother to the clinic with a chief complain
of cough.
• The mother has HIV and got MTCT
prophylaxis some days before her labour.
• The infant got some drugs (her mother
doesn’t remember) for some days after
birth.
• She was not able to buy formula, so has
breast-fed her infant.
23
Case study
• The cough occurred 2
weeks before, with mild
fever (no exact
temperature)
• The infant sucks quite
well, but frequently
vomits due to coughing.
• Examination reveals
dyspnea with in-drawing
chest, SpO2 85%, no
crackles, tachycardia but
no heart murmur
24
Case study
• A clinical diagnosis of PCP is followed by
treatment with a combination of CTX and
methylprednisolon.
• What about ART?
– Wait for:
•
•
•
•
•
Confirming HIV status?
Complete PCP treatment?
Consent of the mother?
Approval of the ART Board?
Others?
25
OI Drug Interactions
• 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

-
-
26
OI Drug Interactions
• Some OI drugs may have decreased blood
levels due to decreased absorption:
OI Drug
Effect on OI drug absorption
when used with:
H2
DDI
PPI Ant-acids
Blockers
Itraconazole,
Ketoconazole
Fluconazole




-
-
-
-
Fluoroquinolones

-
-

27
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Key Points
• For OIs with no disease-specific treatment, ART should
be started ASAP
• Conditions that are caused by immune dysregulation
(malignancy, autoimmune diseases) will improve with
ART
• If CD4 > “severe” level, then ART can wait until the acute
treatment of the OI is completed
• If CD4 < “severe” level, then ART should be initiated
sooner, with careful monitoring for drug toxicity and IRIS
• Be aware of potential interactions between OI drugs and
ARVs
28
Thank You
Questions?
29