ART FINAL, on Training'-April 2008

8/8/2019 ART FINAL, on Training'-April 2008

http://slidepdf.com/reader/full/art-final-on-training-april-2008 1/76

Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents

Dr. M. Dinaker M.D.,

Clinical consultant, APAIDSCON



Guidelines Outline

Overview Initiation of Therapy

Changing Therapy

Special Issues



The best treatmentfor HIV /AIDS is still

³PREVENTION´



Good information about

HIV /AIDS is one of

the best treatments for the disease.







What the Guidelines Address

Laboratory testing (viral load, CD4+

T cells, resistance)

When to initiate therapy When to change therapy

Therapeutic options

Adherence

ART-associated adverse effects

continued



What the Guidelines Address«cont¶d,

Treatment of acute HIV infection

Special considerations in adolescents,

pregnant women, injection drug users, and

patients coinfected with HIV and hepatitis B,

hepatitis C, or tuberculosis

Prevention counseling for HIV-infected patients





Goals of Therapy & Tools to Achieve

them:

Improvement of quality of life

Reduction of HIV-relatedmorbidity and mortality

Restoration and/or preservation of immunologic function

Maximal and durablesuppression of viral load

Selection of ARV regimen Preservation of future

treatment options

Rational sequencing of

therapy Maximizing adherence

Use of resistance testingin selected clinicalsettings

GOALS TOOLS



NACO, May 2007



Please remember««..

ART reduces the viral load, and therefore

reduces the risk of transmission.

Hence, ART should be

integrated into the preventivestrategies also.



- WHO, July 2007





Use of HIV RNA & CD4+ T Cell

Levels to Guide Therapy Decisions

Syndrome consistent with acute HIV

infection Initial evaluation of new HIV diagnosis

Every 3-4 months in the untreated patient

Immediately prior to initiating therapy 2-8 weeks after initiating therapy

Every 3-4 months in patients on therapy

As clinically indicated



The 5 S¶s:«.. Start

Switch

Substitute

Stop

Salvage



Indications for Initiation of Therapy:

Chronic Infection:Clinical

Category

CD4+ T Cell

Count

Plasma HIV

RNA

Recommendation

Symptomatic

(AIDS, severe

symptoms)

Any value Any value Treat

Asymptomatic,

AIDS

<200 cells/µL Any value Treat

Asymptomatic >200 cells/µL

but <350

cells/µL

Any value Treatment should be

offered, with

consideration of pros

and cons



Indications for Initiation of Therapy:

Chronic Infection«.. Cont¶d.Clinical

Category

CD4+ T Cell

Count

Plasma HIV

RNA

Recommendation

Asymptomatic >350

cells/µL

>100,000

copies/mL

Most clinicians recommend

deferring therapy; some will

treat

Asymptomatic CD4+ T cells>350

cells/µL

<100,000copies/mL

Defer therapy



-WHO, July 2006



- NACO, May 2007





Benefits and Risks of Deferred Therapy

BENEFITS Avoid negative effects on

quality of life

Avoid drug-related toxicity

Preserve future drug

options Delay development of drug

resistance

Decrease total time onmedications

RISKS Possibility of irreversible

immune system

depletion

Increased possibility of

progression to AIDS

Possible increased risk

of HIV transmission







Current Antiretroviral Medications:



WHO , JULY 2006



Some popular¶ ³Fixed Drug

Formulations´

AZT + 3TC + NVP (DUOVIR-N*, CYTOCOM-N)

D4T + 3TC + NVP (TRIOMUNE*, NEVILAST*)

AZT + 3TC + EFZ (DUOVIR-E* , CYTOCOM-E)

TDF + 4TC + EFZ (VIRADAY*)



NACO GUIDELINES 2005

Initiate ART at CD4 < 200.

First Line Regimens:- AZT + 3TC + NVP

- d4T + 3TC + NVP



NACO Guidelines 2005 (I) Male / non pregnant females with hepatic

dysfunction / active¶ TB on ATT:

AZT+ 3TC+EFV.

(II) Males / females irresp of pregnancy status

with Normal LFT:

AZT + 3TC + NVP. (III) Pregnant females with abnormal LFT /

active TB on ATT¶ :

AZT + 3TC + ABC.



OTHER RELATED ISSUES«.

NO ROLE FOR MONO OR

DUAL DRUG REGIMEN. EFZ based regimens still OUT of reach

of many. (Attractive once daily kit ddI +

3TC + EFZ is available).

AZT + 3TC + ABC may be an

alternative.

PI based regimens are expensive.



Please refer to

guidelines for individual

drug dosing schedules.



ADVERSE EFFECTS





Adverse Effects: NRTIs

All NRTIs:

Lactic acidosis and hepatic steatosis(higher incidence with stavudine)

Lipodystrophy (higher incidence with

stavudine)



Adverse Effects: NRTIs«cont¶d

Abacavir - hypersensitivity reaction

Didanosine* - GI intolerance, pancreatitis,

peripheral neuropathy (PN) Stavudine* - PN, pancreatitis

Tenofovir - headache, GI intolerance, renalimpairment

Zalcitabine - PN

Zidovudine - headache, GI intolerance, bonemarrow suppression

* Pregnant women may be at increased risk for lactic acidosis and liver

damage when treated with stavudine + didanosine. This combination

should be avoided in pregnant women, if possible.



Adverse Effects: NNRTIs

All NNRTIs:

Rash Drug-drug interactions

Nevirapine ± hepatotoxicity (may be severe andlife-threatening), rash including Stevens-

Johnson syndrome Efavirenz - neuropsychiatric, teratogenic in

nonhuman primates (FDA PregnancyCategory D)





Adverse Effects: PIs

Hyperlipidemia (TG)

Diarrhea / GI intolerance

Insulin resistance and diabetes

Lipodystrophy

Elevated liver function tests, pancreatitis

Possible increased bleeding risk inhemophiliacs

Drug-drug interactions

Indinavir crystalluria



Lipodystrophy



WHO, JULY 2006



At follow up««.analyse ³new

onset´ symptoms:

HIV per se OIs

Drug effectsIRS, Others

IRIS

U NRELA

-TED





When to change therapy?



Differentiate between««

³Substitute´

³Switch´



WHO AUG, 2006



W

HO

AUG2006



WHO

AUG2006



Treatment-Experienced Patients: ARV

Treatment Failure

Causes of treatment failure include:

Patient factors

(CD4 nadir, VL, comorbidities, etc)

Suboptimal adherence

ARV toxicity and intolerance

Pharmacokinetic problems Suboptimal drug potency

Viral resistance



Changing (Switch)

Therapy



Changing Therapy: Considerations

Clinical status

HIV RNA level on 2 tests

CD4+ T cell count

Remaining treatment options

Potential viral resistance

Medication adherence

Patient education



Treatment Regimen Failure:

Assessment Possible causes:

Suboptimal adherence

Medication intolerance

Pharmacokinetic issues

Suboptimal drug potency

Viral resistance

Approach depends on cause of regimen

failure and remaining antiretroviral options

A ti t i l P t ti ll A ti



Antiretrovirals Potentially Active

in Treatment-Experienced

Patients

EnfuvirtideCCR5 inhibitors

Tipranavir

TMC114

D-d4FC (NRTI)

TMC125 (NNRTI)

PA-457

MK-0518

GS-9137





WHO AUG, 2006



Special Issues: Contents

Acute HIV infection

Treatment for children

Treatment for pregnant women Injection Drug Users

Patients with Hepatitis B or C Co-

Infection Mycobacterium Tuberculosis

Prevention Counseling



WHO

AUG

2006







TB & HIV



TB / HIV Co-Infection

Increased risk of progression from

latent¶ to µactive¶ TB

Increased risk of HIV progression



TB/HIV Co-Infection:

Treatment Considerations The treatment of TB in patients with HIV infection

should follow the same principles for persons

without HIV infection

For active TB, initiate treatment ASAP.

Directly observed therapy is strongly

recommended



TB/HIV Co-Infection: Treatment

Considerations«cont¶d.(1) In patients on ARV therapy, evaluate ARV

regimen for interactions with TB drugs

In ARV-naive patients, avoid simultaneousinitiation of treatment for TB and HIV

Consider delay of ARVs for 4-8 weeks

after initiation of TB treatment to avoid

overlapping of adverse reactions and

paradoxical reactions (IRIS).



TB/HIV Co-Infection: Treatment

Considerations«cont¶d.(2) Rifampin/rifabutin-based regimens should be

given at least three times weekly in patients with

CD4+ T cell count <100 cells/mm3.

Once weekly rifapentine is not recommended in

HIV-infected patients

³DOTS´ is effective in HIV co-infection patients.





TB/HIV Co-Infection:Treatment Considerations (4)

Paradoxical reactions (IRIS) occur more

commonly in pts on ARTs. Continue treatment for tuberculosis and

HIV, use non-steroidal anti-inflammatoryagents.

In severe cases consider use of high-dose prednisone (should be taperedover 4 weeks).







W

H

O

AUG

2006



Who, Aug 2006





WHO AUG, 2006



WHO AUG 2006



PA-457

PIs

NNRTI

NRTI

Maturation inhibitors

CCR5Inhibitors

IntegraseInhibitors

TMC278

TMC125

D-d4FC

TMC114

GW640385

Integrase inhibitors

Entry inhibitors

(anti-gp120, CCR5)

GW695634

CXCR4Inhibitors

?

Timeline for ³New´ antiretrovirals

2005 2006 2007 2008 2009



Coreceptor

Binding

CCR5/CXCR4

gp41

gp120

V3 loop

CD4

Binding

CD4

HIV attachment and fusion:

Targets for inhibition

Cell membrane

Virus-Cell

Fusion

BMS-488043

Chemokine

Antagonistseg, SCH D Enfuvirtide

SUMMARY



SUMMARY

ART should be initiated according to guidelines. Know the 5 S¶s.

Adequate knowledge of rationale sequencing,potential side effects and toxicity is a must.

Social factors (including cost of therapy) and co-existent OIs are equally important.

³Adherence´ issues are critical and shouldalways be emphasized to the patient at every

visit. When in doubt, defer¶ therapy and refer to

specialist.



Thank you all

for your kind

attention!

Documents

ART FINAL, on Training'-April 2008