Starting ARVs in the setting of Opportunistic Infections pptx

Starting ARVs in the setting of
Opportunistic Infections
2
Learning Objectives
At the end of this presentation, the participant should be able
to:
•
Cite 3 opportunistic infections where ARV therapy is part of
the treatment
•
Cite 5 opportunistic infections where ARV initiation may lead
to IRS
•
Give the appropriate management for a newly diagnosed
PLWHA on TB therapy who has a CD4 count < 200.
•
Give the dose of EFV that should be used when treating TB
in Vietnam.
•
Cite the recommendation of the MOH of the use of NVP with
a RIF containing TB therapy
•
Cite the best time and clinical conditions that a patient with a
treated OI can be started on ARV therapy
3
Outline of Presentation
•
Introduction
•
In which OIs can you start ARVs right away
and in which can you not?

Tuberculosis – What therapy can we start?
•
Tuberculosis – When can we start therapy?
•
Tuberculosis – Four treatment scenarios.
•
Cryptococcus – When can we start therapy?
•
Side Effects of ARV and OI medications
Starting ARVs in the setting of an active
Opportunistic Infection
Introduction

5
Introduction
•
The decision to start ARVs is a balance
between
–
wanting the immune system to recover in order to fight infection
vs.
–
the risk of drug interactions and side effects
–
the risk of immune reconstitution syndrome
6
Introduction
•
Little data exists on the best time to start ARVs
when the patient is being treated for an OI.

Clinical judgment must be used.
•
Prior starting ARV therapy the patient should be
responding to OI therapy, with no fever and no
active side effects (rash).
•
It is important to know the drug interactions of all
medications before they are prescribed (look it
up!)
7
Guiding principles
•
Always treat the acute OI first
•
Begin ARVs when the patient is clinically stable
•
Be vigilant for drug interactions and overlapping
toxicities
•
Beware of Immune reconstitution syndrome
Do not be afraid to treat!
Starting ARVs in the setting of an active
Opportunistic Infection
In which OIs can you start ARVs right away
and in which can you not?
9
Starting ARVs in the setting of an
active Opportunistic Infection
Some OIs include ARVs as critical components of
treatment. In these OIs, ARV therapy should not be

delayed.
•
Cryptosporidiosis • Microsporidiosis
•
Kaposi Sarcoma
•
Progressive Multifocal Lymphadenopathy
(PML)
10
Starting ARVs in the setting of an
active Opportunistic Infection
In other OIs, ARV therapy can exacerbate
the condition with IRS. In these infections
ARV therapy should be delayed:

•
Tuberculosis • Penicilliosis
•
Toxoplasmosis • Cryptococcosis
•
Pneumocystis Carinii Pneumonia
Starting ARVs in the setting of an active
Opportunistic Infection
Tuberculosis

What therapy should we start?
12
Review of Drug Metabolism
Rifampicin
Induces

Cytochrome
P450
Activiy
Ritonavir
Inhibits
Cytochrome
P450
Activity
13
Rifampin and ARV blood levels
SQV IDV NFV LPV NVP EFV
Rifampin

84%

89%

82%

75%

37%

25%
Finch et al. Arch Intern Med 2002;162:985-92
14
Rifampin and ARV
•
We know we cannot use Rifampin with
Protease Inhibitors (IDV, NFV)

•
But what about using Nevirapine and
Efavirenz with Rifampin?
15
Rifampin and Efavirenz
•
Mean plasma level of 600 vs 800 mg EFV with a RIF
containing TB treatment is not statistically different.
•
Good virological suppression found in
–
91% of patients with EFV 600 mg + D4T/3TC
–
87% patients with EFV 800 mg + D4T/3TC
•
MOH Guidelines give option of EFV 600 mg or 800
mg when taking RIF but recent data shows EFV 600
mg is adequate.
Manosuthi W. AIDS 2005;19:1481-6. Guidelines for Diagnosis and
Treatment of HIV/AIDS, Ministry of Health, Vietnam. March, 2005.
16
Rifampin and Nevirapine
•
There is no difference in the HIV suppression in patients taking
NVP/D4T/3TC + a Rifampin based TB treatment vs those who do
not take RIF (73 and 66% respectively).
•
Despite low NVP levels in 24% patients taking NVP + Rifampin,
82% of these patients had good virological suppression.
•

As per MOH guidelines, substitute EFV for NVP if the patient will
start of RIF and if it is available.
•
But, if EFV not available, do not need to stop NVP containing ARV
therapy in the event one needs to start a RIF based TB therapy.
•
And, if EFV is not available, do not need to wait until after the
induction period of TB treatment is over to start NVP containing
ARV.
Weerawat M et al. CID 2006;43:253-5. Guidelines for Diagnosis
and Treatment of HIV/AIDS, Ministry of Health, Vietnam. March, 2005.
Starting ARVs in the setting of an active
Opportunistic Infection
Tuberculosis

When should we start therapy?
Antiretroviral Therapy and TB
You have just started your HIV patient on TB therapy
Her CD4 count is less than 250
When do you start ARVs?
1. Immediately
2. Wait 2 months until continuation phase
3. Wait until 6 months after TB Rx is completed
4. Wait until immediately after the completion of TB Rx
5. Depends on CD4 count
Slide courtesy of Dr A.L. Pozniak
19
Antiretroviral Therapy and TB
Immediate vs. Delayed ARV
Arguments for delaying potent HIV therapy until TB is

treated:
1. HIV is a chronic disease.
2. Adherence may be compromised.
3. Toxicity management is more complex.
4. Immune restoration may produce IRS or
“paradoxical reactions.”
Slide courtesy of Dr A.L. Pozniak
20
Antiretroviral Therapy and TB
Immediate vs. Delayed ARV
Arguments for initiating potent HIV therapy at the
onset of TB:
1.TB is associated with increased HIV
replication and and HIV disease progression.
2.Potent antiretroviral therapy can reduce HIV
RNA
levels and slow HIV disease progression.
3.HIV therapy reduces risk of developing other
opportunistic infections
Slide courtesy of Dr A.L. Pozniak
21
Study on Initiating ARV Therapy
in PLWHA with TB
Prospective study looking at British patients being
treated for TB and who were newly diagnosed
with HIV.
•
188 patients with a mean CD4 count of 70
cells/mm
3

started ARVs.
•
Outcomes measured:
–
AIDS defining illnesses (ADI)
–
Mortality
Dean et al AIDS
2001
Dean et al AIDS 2002:16(1):75-83.
22
Study on Initiating ARV Therapy
in PLWHA with TB
Results:
•
27/188 patients developed further ADI
–
18 of 92 (20%) had CD4 count ≤ 100 cells/mm3
–
9 of 91 (10%) had CD4 count ≥ 100 cells/mm3
•
Minimum time to ADI developing in patients was
1 month
Dean et al AIDS
2001
Dean et al AIDS 2002:16(1):75-83.
23
Study on Initiating ARV Therapy
in PLWHA with TB
Results:

•
24.5% patients did not start on ARVs
–
39% with CD4 < 100 who did not start on ARVs had an ADI
–
3.5% with CD4 < 100 who started ARV had ADI
•
The majority of patients who died were not on
ARVs 12/16 (81%)
Dean et al AIDS
2001
Dean et al AIDS 2002:16(1):75-83.
24
Study on Initiating ARV Therapy
in PLWHA with TB
Conclusion –
1. Start ARV quickly in patients with CD4 < 100
as they are the most vulnerable to ADI and
death!
2. Since most ADI started at minimum 1 month,
ideally to start as soon as patient tolerates TB
therapy and has a good response….may be
after 2 weeks.
Dean et al AIDS
2001
Dean et al AIDS 2002:16(1):75-83.
Starting ARVs in the setting of an active
Opportunistic Infection
Tuberculosis

Four Treatment Scenarios