Starting ARVs in the setting of Opportunistic Infections pptx

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?... Starting ARVs in the setting of an active Oppor

Starting ARVs in the setting of

Opportunistic Infections

• 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

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

– the risk of drug interactions and side effects

– the risk of immune reconstitution syndrome

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

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?

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)

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:

Starting ARVs in the setting of an active

Opportunistic Infection

Tuberculosis

What therapy should we start?

Review of Drug Metabolism

Rifampin and ARV

• We know we cannot use Rifampin with

Protease Inhibitors (IDV, NFV)

• But what about using Nevirapine and

Efavirenz with Rifampin?

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

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.

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?

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

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

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

• 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.

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

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.

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

Starting ARVs in the setting of an active

Opportunistic Infection

Tuberculosis

Four Treatment Scenarios

ARV therapy in co-infected patients:

Scenario 1

If patient has:

1 Pulmonary TB only

2 No other signs of clinical stage III or IV

3 Not yet on ARVs

Then:

therapy is completed if CD4 < 350.

2 Signs of clinical stage III or IV disease

3 Not yet on ARVs

Then:

1 Start TB treatment

2 Start ARVs after initiation phase of TB

treatment (earlier if patient is severely ill).

Anti-retroviral therapy in co-infected

• Start ARV as soon as patient tolerates

TB meds (between 2 weeks and 2

months) regardless of CD4 count.

• Begin TB therapy (evaluate for potential drug

interactions and additive toxicities).

If CD4 counts are available

CD4 > 350 Treat TB first unless

other WHO stage III or

IV signs are present

CD4 200-350 Start TB treatment first

Start ARVs after initiation phase of TB treatment

CD4 < 200 Start TB treatment then

start ARVs as soon as

TB treatment is tolerated (2 weeks-2 months)

Starting ARVs in the setting of an active

Opportunistic Infection

Cryptococcal Meningitis

When should we start therapy?

Case Study

• 30 year old man presented to the hospital

because of 4 days of fever, severe headache, and blurry vision Lumbar puncture is

performed and India Ink stain is positive for

many Cryptococcus neoformans yeast forms The WBC count is 0 cells/cc 3

Treatment

• Amphotericin B is not available, so the patient is

treated with fluconazole 800 mg by mouth daily This is called the “induction phase” of treatment.

• The patient slowly improves, and after 2 weeks,

his dose is reduced to 400 mg by mouth daily This is called the “consolidation phase” of

treatment His fevers have resolved but he still has some headaches daily.

• Pt is WHO Stage IV, and therefore meets

criteria for ARVs

• As soon as patient is stable on consolidation

phase of Fluconazole, consider beginning

ARVs

– No signs or symptoms of hepatitis on Fluconazole

– Clinical symptoms of OI (headache and fevers) completely resolved

– Completed adherence training

Secondary Prophylaxis

• Remember that after 8-10 weeks of

“consolidation” treatment with fluconazole 400

mg daily, the dose can be reduced to 200 mg daily for secondary prophylaxis

(“maintenance phase”).

– This should continue until his immune system is improving (CD4 > 200) on ARVs for

3-6 months.

Starting ARVs in the setting of an active

Opportunistic Infection

Medication Side Effects

Side Effects – ARV and OI Medications

• Liver toxicity: INH, RIF, PZA and NNRTI’s or PI’s

• Bone marrow suppression: AZT and

Cotrimoxazole

• Peripheral Neuropathy: Isoniazid and D4T

• Renal insufficiency: TDV and Cotrimoxazole

TB and ARV Treatment – Side Effects seen in British Cohort of newly diagnosed PLWHA

of therapy

in 34%

Adverse events in 45% of patients -

Key Points

• ARV Therapy is part of the treatment in Cryptosporidiosis,

Microsporidiosis and PML.

• ARV initiation may lead to IRS in TB, Cryptococcus,

Penicilliosis, Toxoplasmosis and PCP

• A PWLHA with a CD4 < 200 should be started on ARV as soon

as he/she is tolerating TB therapy, within 2 weeks to 2 months.

• EFV 600 mg should be used when treating TB in Vietnam

• MOH guidelines say that it is preferable to give EFV if a person

is taking RIF, but that NVP can also be given with close

monitoring

• The PWLHA should started on ARVs after they have started

treatment for the OI and are showing improvement in their

clinical condition, ideally having no fever and no side effects (rash)

Thank you!

Questions?