therapeutic regimens in hiv

8/12/2019 Therapeutic Regimens in HIV

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Therapeutic Regimens inHIV/AIDS

J. Peter Figueroa

Chief, Epidemiology & AIDSPresented by T. Hylton-KongBlue Cross Symposium, November 16, 2003


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Acknowledgement

Resource material includes slidesfrom:

Dr. John Bartlett Dr. Christopher Behrens Dr. Robert RedfieldReference to: Regional ARV guidelines meeting in

May 2003

Clinical guidelines for Jamaica (in


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HIV/STD Control in JamaicaAchievements

High awareness of HIV/AIDS Increased use of condoms Decline in syphilis & gonorrhea Decline in congenital syphilis cases Protection of the blood supply Slowed HIV spread Averted over 100,000 HIV

infections


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Despite the achievements :

HIV and AIDS

continue to spreadin Jamaica

24% of men & 34% of womenhaving sex with a non-regular partner

do not use a condom in Jamaica


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HIV/AIDS IN JAMAICA

Sero-prevalence among adults 1.5%Estimated No. with HIV/AIDS 22,000No. of persons in need of ARV 8,000

No. of persons currently on ARV 400


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Improving access to

Antiretroviral Drugs

Submission to the Global FundUS$23million over 5 years

National Health Fund

Cost recovery

MAJ AIDS Fund


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Initial Health Care History and examination Laboratory Investigations

HIV education and counseling Treatment of current conditions Vaccination Hep B, HZ, `Flu Case notification Partner notification Refer as necessary


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Healthy Lifestyle Good nutrition, care re eating Rest, relaxation, exercise

Avoid crowds, hospitals and pets Stop smoking, alcohol, drugs Family planning Condom use Family, friends and social support Spiritual health


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HIV diseaseTreatment Principles

Suppress the virus Restore the immune system Treat the complicating illnesses Minimize the risk of resistance & toxicity Improve the quality of life & clinical

outcome TREAT THE WHOLE PERSON, not just

the diseases they have


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Laboratory Tests:Jamaican Guidelines

Must do: HIV, CBC (Hb, WBC, diff,platelets), VDRL, urinalysis

Should do: CD4, renal, LFTs, lipids,CXR, HBsAg, Pap smear,

As indicated: glucose, pregnancy,

amylase

Optional: HIV viral load


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1

10

100

1,000

10,000

100,000

1,000,000

10,000,000

P l a s m a

H I V R N A

Viral Load

CD4 Cells

4-8 Weeks Up to 12 Years 2-3 Years

CD4

C e l l C o un

t

1,000

500

Intermediate Stage AIDS

PrimaryInfection Sero-conversion

CD4 Count, Viral Load andClinical Course


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WHEN TO START: WHO

CD4 count availableWHO stage IV (AIDS)WHO stages I-III + CD4


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When Should HAART be Initiated?DHHS Guidelines

Clinical Category CD4 count Viral Load Recommendation

Symptomatic (AIDS,severe Sx)

Any value Any value Treat

Asymptomatic, AIDS < 200/mm3

Any value Treat

Asymptomatic > 200/mm 3

but < 350Any value Treatment should

generally beoffered

Asymptomatic > 350/mm 3 > 55,000

copies/mL

Some experts

would recommendinitiating treatment

Asymptomatic > 350/mm 3 < 55,000copies/mL

Many expertswould defertherapy andobserve

DHHS Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults andAdolescents, February 4, 2002, Table 6.


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Improving Adherence:before Initiation of Therapy

Assess patient's understanding andacceptance of the regimen: negotiatedplanInvestigate and manage medicalbarriers to adherence

Try to use simple regimens bid or better without food requirements if possible

Adapted from: Miller et al., The AIDS Reader 10(3):177-185, 2000.


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Classes of Antiretroviral Agents

RNA DNA

HIV

Nucleus

Host Cell

Nucleoside Analogues (NRTIs)

Non-Nucleosides (NNRTIs) Protease Inhibitors (PIs)

RT


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Highly Active AntiretroviralTherapy (HAART)

Combination of at least 3 drugs, usually: NNRTI - based regimens (2 NRTIs + 1

NNRTI) NRTI - based regimens (3 NRTIs) PI - based regimens (2 NRTIs + 1-2 PIs)

Therapy with only one or two ARV drugsallows HIV to overcome therapy throughresistance mutations


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WHAT TO START

2NRTI + 1NNRTI 3 NRTIs PI

AZT/3TC + NVPAZT/3TC or EFVd4T/3TCd4T/ddI

AZT/3TC*/ABC AZT/3TC* + IDVor NFV

or LPV/r orIDV/r or SQV/r

*d4T/3TC or d4T/ddIAZT = ZDV = Zidovudine NVP=Nevirapine IDV=Indinavir3TC = LMV = Lamivudine EFV=Efavirenz NFV=Nelfinavird4T = STV = Stavudine ABC=AbacavirLPV/r=Lopinavir/ritonavir SQV/r=Saquinavir/ritonavir


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Choice of initial regimenby baseline Viral Load (VL)

VL > 100,000 Proven

Kaletra + 2 NRTIs Efavirenz + 2 NRTIs

Unproven Boosted PI + 2

NRTIs 3 NRTIs + PI 3 NRTIs +

Nevirapine NRTI/NNRTI/PI

VL < 100,000

LPV/RTV + 2 NRTIs Efavirenz + 2 NRTIs Nevirapine + 2

NRTIs 1-2 PIs + 2 NRTIs AZT/3TC/Abacavir


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Zidovudine Dosing: 300 mg bid, or 200 mg tid Interactions: no food interaction Toxicity

Sx: Fatigue, insomnia, nausea, abdominaldiscomfort, headaches, myalgia

AE: Granulocytopenia, neutropenia,

anemia,pigmentation of nail beds(melanychia), lactic acidosis, hepatic steatosis


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Lamivudine Dosing: 150 mg bid Interactions: no food interaction

Toxicity Sx: Mild abdominal discomfort, occasionalnausea

AE: Minimal


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Efavirenz Dosing: 600 mg qhs Interactions: take on empty

stomach(fat increases absorption)

Toxicity Sx: Insomnia, nightmares, poor

concentration, mood change,dizziness, rash, nausea,

dysequilibrium AE: Rash, hepatitis, depression,

psychosis


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Nevirapine Dosing: 2 weeks of 200 mg. qd, then 200

mg bid Interactions: no food interaction Toxicity

Sx: Rash, fever, nausea AE: Rash, Stevens-Johnson syndrome,

hepatitis


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Indinavir Dosing: 800 mg q 8 hours1 Interactions: empty stomach, or with non-fat milk Toxicity

Sx: Nausea, diarrhea, flank pain, hematuria, dry lips,dry skin

AE: Hematuria, pyuria, increased creatinine,hyperbilirubinemia, xerosis, fat redistribution, lipidabnormalities


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Optimal Response to Initial HAART

Steep drop in viral load toundetectable levels (< 50 copies/mL)

Rise in CD4 count

Immune Restoration


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Optimal Response to Therapy

1.0 log drop after 2-8 weeks treatment

Continued 1.0 log drop monthly Undetectable virus after 4-6 months

treatment

Durable, complete suppression


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Antiretroviral Therapy: OptimalResponse

10

100

1000

10000

100000

1000000

0 1 2 3 4 5 6 7 8

Viral Load

HAART Initiated

50 50

Time (months)

C D 4 c o u n

t ( c e l

l s / m m

3 )

V i r a l

L o a

d ( c o p

i e s / m L )


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Antiretroviral Therapy: OptimalResponse

10

100

1000

10000

100000

1000000

0 1 2 3 4 5 6 7 8

0

100

200

300

400

500

Viral Load

CD4 Count

HAART Initiated

50 50

Time (months)

C D 4 c o u n

t ( c e l

l s / m m

3 )

V i r a l

L o a

d ( c o p

i e s / m L )


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SWITCHES FORVIROLOGIC FAILURE

Initial Regimen New Regimen

AZT/3TC + NVP or EFV ddI/d4T + PI

AZT/3TC/ABC EFV or NVPLPV/r ddI/d4T

AZT/3TC + PI ddI/d4T/EFV or NVP


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Predictors of ARV Success

Low baseline viremia High baseline CD4+ T cell count

Rapid decline of viremia Decline of viremia to


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0

20

40

60

80

100

>95 90-95 8090 70-80


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A dh erenc e i s a sk i l l to belearned (Frank , 1997)

Patient must be able to: Understand the regimen Believe they can adhere Remember to take medication Integrate regimen into lifestyle Problem solve changes in schedule

& routines


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LESSONS FROM HAARTGOOD NEWS 1996-2003

Remarkable benefit: mortality,hospitalization, AIDS rates 50-80%

Immune reconstitution even withbaseline CD4 count


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LESSONS FROM HAARTBAD NEWS 1996-2003

Cannot cure HIVViral replication continues even

with no detectable virusLong-term toxicity lipodystrophyIncreasing resistance

Treated patients 50%Untreated patients 10-20%

Adherence 95% rule


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Antiretroviral Induced MetabolicToxicities

Mitochondrial toxicity Lactic acidosis Hepatitis/pancreatitis Peripheral neuropathy Myopathy

Hyperlipidemia hypertriglyeridemia, hypercholesteremia

Redistribution of fat Insulin resistance Bone Disorders

osteopenia , osteoporosis, osteonecrosis


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Physical Manifestations ofLipodystrophy


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Improve the Care of Persons

Living with HIV/AIDS- Access to a health provider- Confidentiality and respect- Counseling and psychosocial

support- Quality of clinical management- Support for home care- Training of health staff- Access to anti-retroviral therapy

therapeutic regimens in hiv

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