Recent Advances in the Management of Hiv Infection

8/6/2019 Recent Advances in the Management of Hiv Infection

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1R E C E N T A D V A N C E S IN TH E

M A N A G E M E N T O F H IV IN FE C T IO N

:Moderator Dr Mohandas Rai:Speaker Dr Ashwini Mandanna M


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R O A D M A P

&INTRODUCTION HISTORY PREVALENCE MODES OF TRANSMISSION

&STRUCTURE LIFE CYCLE ANTIRETROVIRAL AGENTS NEWER INVESTIGATIONAL DRUGS

HIV VACCINES

T R E A T M E N T G U ID E LIN E S


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IN T R O D U C T IO N

R e tro viru s

q Classification

.1 Oncovirus .2 Lentivirius .3 Spumavirus

-Origin pan troglodytes species ofchimpanzees

Antiretroviral drugs


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( )HUMAN IMMUNODEFICIENCY VIRUS HIV

TYPES OF HIV

.1 HIV 1

.2 HIV 2


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HISTORY

,AIDS was first reported June 5 1981 Gay related immune deficiency The 4H disease -AIDS July 1982 - -Earliest known positive identification HIV

- -1 virus Congo in 1959 and 1960 into thehuman population from chimpanzees


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HISTORY OF ANTIRETROVIRAL DRUGS

:007 Maraviroc

2008 :Etravirine


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ATEST FDA APPROVAL ENERIC NAMEUSION INHIBITOR

2OO3 ( - )ENFUVIRTIDE T 20ORECEPTOR ANTAGONIST2007 MARAVIROC

UCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS1987 ( )ZIDOVUDINE AZT

2003 ( )EMTRICITABINE FTC

( )ON NUCLEOSIDE REVERSETRANSCRIPTASE INHIBITOR NNRTI s2008 ETRAVIRINE

ROTEASE INHIBITOR s2003

,ATAZANAVIR FOSAMPRENAVIR


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PREVALENCE IN INDIA

( )-NACO National AIDS Control Organisation 2008report

Estimated number of people living with HIV/AIDS, 2007

People living withHIV/AIDS

2.31 million

An estimated 39% are female and 3.5% are children.


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HIV TRANSMISSION RISK OF DIFFERENTROUTES


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INCUBATION PERIOD

%75 of HIV infected persons develop AIDSon an average of 10 years .Incubation period

,During this time the virus is seriouslydamaging the infected person s immune system.


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STRUCTURE OF HIV VIRUS

urface P

integraseeverse transcriptaseag protein

A binding Pprotease

apsid protein

Transmembarne


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LIFE CYCLE OF HIV

Entry inhibitors


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( )GOALS OF ANTIRETROVIRAL THERAPY ART

Clinical goal Prolongation of life & improvement of qualityof life

Virological goal Greatest possible reduction in viral load for aslong as possibleImmunological goal Immune reconstitution that is both

quantitative & qualitative

Therapeutic goal Rational sequencing of drugs in a fashion thatachieves the above 3 goals while maintainingtreatment options, limiting drug toxicity &

facilitating adherenceReduction of HIVtransmission in individuals

By suppression of viral load


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CLASSIFICATION OF DRUGS USED INART

.I Nucleoside reversetranscriptaseinhibitors

.II Non nucleosidereverse transcriptase

inhibitors

.III Proteaseinhibitors

.IV Entry inhibitors

.V Integraseinhibitors

NevirapineEfavirenzDelaviridineEtavinine

SaquinavirIndinavirRitonavirNelfinavirAmprenavirLopinavir

AtanavirFosamprenavirTipranavirDarunavir

ZidovudineDidanosine StavudineZalcitabine

LamivudineAbacavirTenofovir disoproxil

emtricitabine

Enfuvirtide

Maraviroc

Raltegravir


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NUCLEOSIDE REVERSE( )TRANSCRIPTASE INHIBITORS NRTI

Zidovudine ZDV Didanosine ddI Stavudine d4T Zalcitabine DDC Lamivudine 3TC Abacavir ABC Tenofovir disoproxil - ( )-TDF nucleotide

2005

Emtricitabine -FTC 2003


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NRTIS GENERAL CONSIDERATIONS

/Nucleoside nucleotide analougs No activity on already infected cells

& , ,S p e ctru m of a ctivity H IV 1 2 H B V H TLV

S E m ain ly d u e toinhibition of mitochondrialDNA polymerase Gamma


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NRTIS

- , - - , - ,abine DDC Emtricitabine FTC Lamivudine 3TC Abacavir ABC


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NRTIs MECHANISM OFACTION

Mechanism of action :- Phosphorylation

- Lack 3-OH group or have azido group :falsely incorporated into HIV genome,

premature termination of chain elongation.


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NRTIs contd

= - %, Absorption 60 95 least didanosine ,Food alters A of zalcitabine didanosine T /12 -ranges between 1 10hrs / , ( )Dosing OD BD except zalcitabine TID Not substrates for CYP450 enzymes ,OT TO BE USED AS MONOTHERAPY Resistanceore to thymidine analogues

Zidovudine Stavudine Didanosine Zalcitabine LamivudineEmtricitab Abacavir


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ZidovudineAZT

Stavudine DidanosineDDI

Zalcitabineddc

Lamivudine3-TC

Emtricitabine

AbacavirABC

Analogue:Thymidine

Thymidine Adenosine Cytidine Cytidine Cytidine Guanosine

Dose:200mg q8h or300 mgbid

60 kg: 40mg bid


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Individual NRTIsZidovudineAZT

Stavudined4T

DidanosineDDI

Zalcitabine Lamivudine3TC

Emtricitabine

AbacavirABC

CI/ Caution:Blooddyscrasia,Othermyelosuppress

ant drugs

Pregnancy,Otherneuropathicdrugs-Peripheral

neuropathy(PN)

Gout, Visualproblem,PancreatitisNeuropathy

Pancreatitis,Hepatitis

In children Pancreatitis,dose reductionin renalimpairment

WithHepatotoxicdrugs

-

DI: AZT+d4TPCTProbenecid,Fluconazole,Valproateincreasetoxicity

ddI+d4T-Increases PN,pancreatitis

GanciclovirAllopurinolincreaseconcentrationantacids

ddI, 3TC,d4T reduceits efficacy

Cotrimoxinhibits renalexcretionEmtricitabinehas similarMOA- not to becombined

Drugs whichare activelysecreted bytubulesTrimethoprim, lamivudine

Alcohol


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TENOFOVIR

-Prodrug enofovir disoproxil fumarate ,,hydrolyzed to Tenofovir Phosphorylated

- -Analogue of adenosine 5 monophosphate ,In adults dose of 300mg OD = %, ,A 25 negligible protein binding

T /12= ,17hrs : &Excretion glomerular filtration tubular

secretion :SE acute renal failure / ,HIV 1 2 HBV


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Serious Side Effects of NRTIs

Drug Side Effects

3TC Pancreatitis, peripheral neuropathy

ABC Hypersensitivity reactions, pancreatitisAZT Bone marrow suppression

d4t Pancreatitis, peripheral neuropathy

ddC Peripheral neuropathy

ddI Pancreatitis, peripheral neuropathy, retinaldepigmentation


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Drug Interactions of NRTIs

Dr ug Inte ra c tions

AZT Drugs associa ted w ith bone marrowsuppressionDrugs which increase Z DVconcentration

d 4T S ho uld no t be ad m in istere d w ith AZTbecause of po tential antagonism

ddI Decreases the absorption of

ketaconazole, itracona zole, anddapsone

3T C N o know n dru g interaction s

A BC N o kn ow n d ru g in teraction s


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NON NUCLEOSIDE REVERSETRANSCRIPTASE INHIBITORS

Nevirapine NVP E fa v ire n z EFV D e la v irid in e DLV E tra v irin e ETV


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NON NUCLEOSIDE REVERSE TRANSCRIPTASE( )INHIBITOR NNRTI S

,NNRTI s inhibit RT directly without the need for/chemical modification phosphorylation

Active only against HIV 1

N o a ctivity a g a in st h o st ce ll D N A p o lym e ra se Undergo hepatic metabolism

: - .E t 2 4 7 2 h o d d osin g Limitation Advere effects mild- rashes

rarely stevens johnsonssyndrome


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-N N R T IS S IT E O F A C T IO N

MECHANISM OF ACTION


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MECHANISM OF ACTION-NNRTIS


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N E V IR A P IN E

- ,H ig h ly lip o p h ilic d ru g cro sse s p la ce n ta fo u n d in b re a stm ilk

S in g le d o se e ffe ctive in p re ve n tin g H IV tra n sm issio n fro mm o th er to n ew b orn

ra d u a l in cre m e n t in d o se re q u ire d a s it in d u ce sts o w n m e ta b o lism :o se 0 0 m g o n ce d a ily fo r first 1 4 d a y s 0 0 m g tw ice d a ily - &E lim in a tio n oxid a tive m e ta b o lism in vo lvin g C Y P 3 A 4C Y P 2 B 6 / -E t1 2 -25 30h / : , A E ra sh e s ra re ly Ste ve n s Jo h n son s syn d ro m e

In cre a se s m e ta b o lism o f d ru g s m e ta b o lise d b y C Y P 3 A 4


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D E LA V IR D IN E


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EFAVIRENZ

First retroviral drug to be taken once aday

: -E t 40 55 h %99 bound to plasma protiens :Elimination CYP2B6 Mod inducer of CYP3A4 & /Teratogeneicty CNS S E

, -Rash rare SJ syndrome :Dose 600mg od


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( - )E TR A V IR IN E T M C 1 2 5

Approved in 2008 Effective against strains resistant to

other drugs in the same class

%99 bound to plasma

, ,Metabolized by CYP3A4 CYP2C9 CYP2C19 No unchanged drug in urine :E t 41h OD dosing

Serious Side Effects of


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Serious Side Effects ofNNRTIs

Drug Side Effects

NVP Rash, fever, nausea, headache,

diarrheaEFV Rash, diarrhea, fever, cough, nausea

DLV Not approved for use in children


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Drug Interactions of NNRTIs

Drug Interactions

NVP Lowers levels of rifampin

Should not be administeredwith ketoconazole or oralcontraceptives

EFV Decreases levels of rifampin,

rifabutin, clarithromycin,saquinavir, indinavir,lopinavir

PHARMACOKINETIC PROPERTIES


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PHARMACOKINETIC PROPERTIESOF NNRTI S

,Good oral bioavailability no major alterationafter food

High plasma binding

Majority metabolized by CYP3A4

,Nevirapine efavirene induction theirmetabolism

,Efavirene delavirdine inhibit CYP3A4


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PROTEASE INHIBITORS

Saquinavir SQVIndinavirIDV

RitonavirRTV

Nelfinavir NFV

Amprenavir APV

LopinavirLPV

Atazanavir ATV

Fosamprenavir FPV


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PROTEASE INHIBITORS

Peptide like chemicals Inhibit action of viral aspartyl protease Protease is a -homodimer essential for

catalysis revent proteolytic cleavage of HIVpolyproteins Prevents the metamorphosis of HIV virus

particles into their mature infectious

-form release of immature and noninfectious forms


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MECHANISM OF ACTION PIs


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P R O T E A S E IN H IB IT O R S

Metabolized by hepatic oxidative metabolismby CYP3A4 except Nelfinavir

R -itonavir most potent inhibitory effect of& -CYP3A4 saquinavir least

This interaction of ritonaviris used toboost levels of other PI s , & :Ritonavir nelfinavir amprenavir moderate

&inducers of CYP3A4 glucuronosyl S-

.transferase -PI s are substrate of p glycoprotein


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Drug Interactions of PIs

Drug InteractionsSQV Levels are increased 3 fold

or greater by RitonavirAPV Reduces Rifabutin 50%

when used concomitantly


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Drug Interactions of PIs

Drug Interactions*

NFV Decreases level of oralcontraceptives

RTV Decreases level of oralcontraceptivesIncreases metabolism oftheophylline

IDV Reduces rifabutin 50% when usedconcomitantly

*All PIs have multiple drug interactionsbecause they are metabolized byctyochromeP450 3A


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PROTEASE INHIBITORS


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I Adverse effects Abnormalities of lipid profile

,Hyperglycemia insulin resistance

Redistribution of fat

Osteoporosis on long term use

Gastrointestinal complaints


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edistribution of fat


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,Tip ra n a vir D a ru n a vir

Newer PI s for treatment of patients withresistance to other PI s

- &Active against HIV 1 2 Active in resistant cases Taken in combination with ritonavir Avoid in sulfa allergy as it contains a

sulfa moiety


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E N T R Y IN H IB IT O R S

:Chemokine CCR5 Receptor Blockers Maraviroc MVC Blocks binding of gp 120

:Fusion Inhibitors -Enfuvirtide T 20

CXCR4- co receptor is also a good targetfor new drug development


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MARAVIROC

Only drug that targets host protein licensed in 2007 Vicriviroc: CCR5 receptor antagonist- trial

Oral bioavailability is 20-30% 76% plasma protein binding Metabolised by CYP3A4 Et : 11 h No dose adjustment for renal and hepatic

impairment Excellent penetration into cervicovaginal

fluid

MECHANISM OF ACTION:


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MECHANISM OF ACTION:MARAVIROC

MARAVIROC


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MARAVIROC

Adverse effects: Hepatotoxicity,nasopharyngitis, fever, cough, rash,abdominal pain, dizziness, fever,musculoskeletal symptoms

Baseline evidence of predominant CCR5tropic virus

3 doses

With CYP3A4 inhibitors: 150 mg Bd With CYP3A4 inducers: 600 mg bd

With other drugs: 300 mg bd

Baseline phenotyping: expensive

ENFUVERTIDE- FUSION


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ENFUVERTIDE- FUSIONINHIBITOR 36 AA synthetic peptide Not effective against HIV 2 Binds to gp41 subunit of viral envelope Given by subcutaneous route CYP450 system not involved in metabolism No cross resistance

Mutation in gp41 codon can lead to

resistance Local injection reactions,

hypersensitivity reactions, increasedrate of bacterial pneumonia

90 mg SC bid

MECHANISM OF ACTION OF


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MECHANISM OF ACTION OFENFUVERTIDE

-IN T E G R A S E IN H IB IT O R S


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IN T E G R A S E IN H IB IT O R SRALTEGRAVIR

FD A a p p ro va lin O cto b e r 2 0 0 7 &Pote n t ag a in st b o th H IV 1 2 ,4 0 0 m g b d T /12 - 9hrs Fat meal increases AUC: 2 fold %8 3 p lasm a p rotein b ou n d -U G T m e ta b o lism - , ,S E d ia rrh e a C P K e le v a tio n Nausea, rash

MECHANISM OF ACTION :


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MECHANISM OF ACTION :RALTEGRAVIR


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Antiretroviral Resistance

Can be transmitted from apatient with a drug-resistant

strain

Can develop under selective drug

pressure

Can be relative to drug

concentration


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Antiretroviral Resistance

Single mutation Resistance

(e.g. lamivudine,

emtricitabine, NNRTIs)

Accumulation of multiple

mutations Resistance

(e.g. many NRTIs, protease inhibitors)

d


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Newer drugs

HIV reverse transcriptase inhibitors1.Nucleoside analogs

Apricitabine

experimental nucleoside reversetranscriptase inhibitor (NRTI).

Phase IIIstudies for the treatment of HIVinfection.

in the same manner as traditional NRTIs

d


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Newer drugs

2.Non-nucleoside analogsRilpivirine (TMC278)- (TMC278)

investigational diarylpyrimidine derivative

non-nucleoside reverse transcriptaseinhibitor (NNRTI)

Phase IIb and Phase III trials for thetreatment of HIV infection in treatment-nave patients.

DapivirineCapravirine

NEWER DRUGS


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NEWER DRUGS

4. Maturation inhibitorsBevirimat PA-457

betulinic acid derivative first-in-its-class maturation inhibitor. Phase II studies to determine its use as a

treatment for assigned fast-track status by the FDA as

of January 2005.

NEWER DRUGS


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NEWER DRUGS

5. INTEGRASE INHIBITORElvitegravir

GS 9137

low-molecular-weight, highly selectiveintegrase inhibitor that shares the corestructure of quinolone antibiotics

Phase II trials for the treatment of HIV-1infection in treatment-naive and-experienced patients.

Ib li b


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Ibalizumab

TNX-355 nonimmunosuppressive, humanized IgG4,

anti-CD4, domain 2 monoclonalantibody that prevents HIV entry intohuman cells.

Phase II trials as part of combinationtherapy for the treatment of HIV-1infection in treatment-experiencedpatients

granted fast-track status by the FDA inOctober 2003.

Intravenous infusion.

Vi i i l t


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Vicriviroc maleate

CCR5 receptor antagonist designed to blockthe entry of HIV into CD4 cells.

Studies being discontinued due to increaseincidence of cancer

BMS-378806 entry inhibitor of HIV-1 that targets the viral

envelope protein also being investigated in formulations for

vaginal administration for the prevention ofHIV-1 transmission when used incombination with other vaginalmicrobicides


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rugs in the pipeline -embrane fusion inhibitors . -T 1249 -Peptide that interferes with gp41 mediated fusion

Phase II . Sifurvitide -interferes with gp41 mediated fusion Phase I ther attachment inhibitors . extran sulfate -Possible charge mediated attachment

,interference binds gp120 and inhibits CXCR4 interaction Phase I


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rugs in the pipeline .PRO 2000 binds to CD4 and interferes with gp120

binding ( )as topical microbicide Phase II . -yanovirin N ,Binds to gp120 interferes with CD4 and

( )CXCR4 interactions as topical microbicide Preclinical


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rugs in the pipeline IV protease inhibitors .1 Elaprevir .2 Boceprevir .3 Brecanavir


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ru g s in th e p ip e lin e n te g ra se in h ib ito r E lvite g ra vir

P h a se III

th ers d ru g s fo r to p ical u se .1 C a rra g u a rd -sea w ee d po lym er en try

[ , , , ]in h ib ito r H IV 1 H IV 2 H S V H PV P h a se III .2 Te n o fo vir g e l

P h a se IIb

V A C C IN E S


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V A C C IN E S

.T h e p a th fo rw a rd is n o t cle a r I th in k th e re.is ag re e m e n t o n th a t A n yb o d y w h o ta lks

a b o u t a tim e lin e fo r a va ccin e is b e in g.silly a n d u n in fo rm e d


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IV Vaccine

- :LV A C H IV ca n ary p o x viru s e n co d e do co n ta in 3 sy n th e tic H IV g e n e s a n dm o d ifie d g p 1 2 0

:IDSVAX gp120 subunit

Highly active


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AART Highly activeantiretroviral therapy

nititiation of combina tion of 3 ormore drugs of 2 different classes

onotheraphy contraindicated

tarted in 1996 THE GOAL OF THE REGIME IS TO

MAXIMALLY SUPRESS HIVREPLICATION SO THAT THE PT CANATTAIN MAXIMUM IMMUNITY


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THE NATIONAL PROGRAMME PROVIDES THEFOLLOWING COMBINATIONS FOR FIRST LINE


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FOLLOWING COMBINATIONS FOR FIRST-LINE

REGIMENS

(i) Stavudine (30 mg) + Lamivudine (150mg)

(ii) Zidovudine (300 mg) + Lamivudine

(150 mg)(iii) Stavudine (30 mg) + Lamivudine (150

mg) + Nevirapine (200 mg)(iv) Zidovudine (300 mg) + Lamivudine

(150 mg) + Nevirapine (200 mg)(v) Efavirenz (600 mg)(vi) Nevirapine (200 mg)

Fixed-dose combinations


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Easy to use Have distribution

advantages(procurement and stock

management) Improve adherence to treatment

Reduce the chances of development ofdrug resistance.

The current national experience shows thatbid (twice a day) regimens of FDCs arewell tolerated and complied with.

Principles for selecting the


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p gfirst-line regimen

1. Choose 3TC (lamivudine) in allregimens

2. Choose two NRTI - 3TC with (AZT or

d4T) 3. Choose one NNRTI (NVP or EFV)

NNRTI BASED

PI BASED

First choice:


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First choice:

AZT + 3TC + NVP (Hb > 8 g/dl)Second choice:d4T + 3TC + NVP

ubstitute NVP with,FV for patients withB or toxicity to NVP


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Ideally, second-line regimens should include atleast three active drugs;

one of them from a new class, in order toincrease the likelihood of the success of thetreatment and to minimize the risk of cross-resistance.

The PI class should be reserved for second-linetreatments.

Immune Reconstitution


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Inflammatory Syndrome (IRIS)

Different from clinical failure A paradoxical worsening of preexisting,

untreated, or partially treated

opportunistic infections Clinical manifestation of a sub-clinical

infection that was already present atbaseline, brought about by HAART-

induced reconstitution of the immunesystem Typically seen within the first several

weeks after initiating HAART

Immunologic Failure


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Immunologic Failure

Fall in CD4 counts more than 30% frompeak value or

A return of CD4 count to, or below, the

pre-treatment baseline Not usually not seen for several months

or maybe years after starting successfulART.

CD4 count can take a long time to comeback up even on effective ART, and maynever reach a normal level if initiallysignificantly suppressed

Virologic Failure


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Virologic Failure

Failure of viral load to becomeundetectable after 24 weeks of ART(failure to suppress)

Reappearance of detectable virus after aperiod of undetectability (loss ofvirologic control)

Less than one log (10-fold) decrease in

viral load from baseline after 6-8 weeksof HAART

Need to ensure that failure is not due to

lack of adherence.

Virologic Failure with non-initial


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gSuppression

. , ; ,Courtesy of David H Spach MD NW AETC University of Washington

Virologic Failure after Initial Response


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Virologic Failure after Initial Response

M e d ica tio n s S ta rte d

50 50

. , ; ,Courtesy of David H Spach MD NW AETC University of Washington

Causes of Failure of Therapy


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Causes of Failure of Therapy

Poor adherence most common and importantreason

Viral resistance

Diminished efficacy of ARVs

Decreased absorption of ARVs Drug-food interactions (eating/not-eating with

meds malabsorption)

Drug-drug interactions

Other disease processes in GI tract Colitis, gastritis, diarrhea lead to rapid transit

times in intestines

Inadequate dosage

Increased metabolism

Time Course of Treatment


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86Failure

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Which Measure of Treatment


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Failure Should be Used?

Virologic failure precedes immunologic &clinical failure

Periodic viral load screening therefore

offers advantage of detecting treatmentfailure earlier, when more options mayexist for subsequent treatmentregimens

However, viral load testing is also veryexpensive: Is the benefit of earlierdetection worth the cost?

Lab Grading of Adverse Events in Adults


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gand Adolescents (ACTG)

Item Grade 1 Grade 2 Grade 3 Grade 4

Hgb (g/dl) 8 - 9.4 7 7.9 6.5 - 6.9 < 6.5

Platelets(/mm3) -- -- 10

Bilirubin((ULN) -- -- 3-7.5 >7.5

Creatinine(mg/dl) -- -- 1.2-1.5 >1.5

* =ULN Upper limitof normalv a lu e

Clinical Grading of Adverse Events in


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gAdults and Adolescents (ACTG)

Item Grade 1 Grade 2 Grade 3 Grade 4

Peripheralneuropathy

Milddiscomfort&/orimpairment

Moderatediscomfort &/orimpairment

Severe discomfort&/or impairment;sensory loss toknee and wrist

Incapacitating ornot responsive tonarcotics;sensory loss

involves limb &trunk

Rash Erythema,prurius

Diffusemaculopap-ular

rash or drydesqua-mation

Vesiculation,moist

desquamation orulceration

Erythemamultiforme, SJS,

or TEN

Changing Therapy Due to


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Toxicity- Specific Exchanges

d4T induced neuropathy or pancreatitis:switch to AZT

AZT induced anemia: switch to d4T

EFV induced persistent CNS toxicity:switch to NVP

NVP induced hepatotoxicity or non-lifethreatening severe rash: switch to EFV

NVP induced life threatening rash like SJS:switch to PI

Discontinuation for Severe


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91Toxicity

If severe toxicity identified, need to stopALL HIV drugs

Do not reinitiate ART until toxic effect has

resolved When stopping NVP, do not re-challenge

Substitute new HIV drug for the drug thatcaused the toxicity, if known (e.g., if

NVP hepatotoxicity, substitute EFV)

ART in Pregnant Women


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ART in Pregnant Women

first-line ART regimens for


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pregnant women

AZT + 3TC + NVP EFV can be used as a substitute for NVP if

there are contraindications to NVP, suchas hepatotoxicity and rash.

EFV caution :risk of foetal teratogenicityduring the first trimester of pregnancy.

Women should be counselled thoroughlyon exposure and risk

good paediatric follow-up is essentialafter the delivery of the infant.

PROPHYLAXIS VERTICAL


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TRANSMISSION

Longer duration of antepartum antiretroviralprophylaxis

HIV-infected pregnant women who do not requiretreatment for their own health should also

receive three-drug combination antiretroviralregimens for prophylaxis of perinataltransmission.

The use of ONLY zidovudinePROPHYLAXIS-

controversial With plasma HIV RNA levels


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INTRA PARTUM

Intrapartum I V zidovudine

HIV-infected pregnant women

regardless of their antepartumregimen, to reduce perinataltransmission of HIV (AI).

omen o ave oReceived Antepartum


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Received AntepartumAntiretroviral Drugs Zidovudine- 2 mg per kg body weight intravenously

over 1 hour, followed by continuousinfusion of 1 mg per kg body weight per

hour

POST EXPOSURE


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PEP must be initiated as soon as possible,preferably within 2 hours

There are two types of regimens: Basic regimen: 2-drug combination Expanded regimen: 3-drug combination


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ons era ons or o- n ec onof


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ofTuberculosis and HIV


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REFRENCES


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REFRENCES

GOODMAN & GILMAN'S THE PHARMACOLOGICAL BASIS OFTHERAPEUTICS 12TH EDITION

HARRISONS PRINCIPLES OF INTERNAL MEDICINE- 17TH EDITION

Rang & Dale pharmacology- 5th edition

Katzung 11th edition

www.aidsinfo.nih/gov www.naco.org

www.who.int

Antiretroviral Therapy Guidelines for HIV-Infected Adults andAdolescents Including Post-exposure- NACO

Guidelines for HIV care and treatment in Infants and children- NACO

R E FR E N C E S
http://www.aidsinfo.nih/govhttp://www.naco.org/http://www.who.int/http://www.who.int/http://www.naco.org/http://www.aidsinfo.nih/gov


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Pa th o g e n e sis o f Lip o d ystro p h y a n d Lip id A b n o rm a litie s in Pa tie n ts. . . ,Ta kin g A n tire tro v ira l T h e ra p y Pa trick W G M a llo n N a tio n a l,C e n tre in H IV E p id e m io lo g y a n d C lin ica l R e se a rch U n iv e rsity o f

, ,N ew S ou th W a les S yd n ey A u stralia

- : . .AV E RT AV E RTin g H IV an d A ID S w w w ave rt org

:A w o rld first V a ccin e h e lp s p re v e n t H IV in fe ctio n -CR5 antagonists in the treatment of treatment naive- .atients infected with CCR5 tropic HIV 1 BredeekUF ,arbour MJ . , ,University of California Los Angeles Division of

, ,Infectious Diseases School of Medicine Olive View UCLA Medical, . , , ,Center 14445 Olive View Dr 2B182 Sylmar CA 91342 USA

evere cutaneous hypersensitivity reactions duringreatment of tuberculosis in patients with HIV infection.n Tanzania ukes CS ,SugarmanJ ,CegielskiJP ,LallingerGJ ,MwakyusaDH . , ,Department of Medicine Duke University

, , .Medical Center Durham North Carolina e r s p e c t i v e -Drug Drug Interactions With Newer Antiretroviral

AgentsInternational AIDS Society USA Topics in HIV MedicineVolume 16 Issue 5 December 2008

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, , . ,Babu2 Roberto Di Santo3 Damian J McColl4 Jan Weber5 and Miguel, -E Quiones Mateu5

; ; :AIDS Reviews 2007 9 162 Maturation Inhibitors a New Therapeutic: .Class Targets the Virus Structure , .Karl Salzwedel1 David E

Martin1 and Michael Sakalian2

; . . .New antiretroviral drugs R M Gulick Cornell HIV Clinical Trials, ,Unit Division of International Medicine and Infectious Diseases

, , , Weill Medical College of Cornell University New York New York

USA . ; : - . - .AIDS Rev 2007 9 173 87 Immunizations in HIV Infected Adults Pablo

, , , -Rivas Mara Dolores Herrero Sabino Puente Germn Ramrez;Olivencia and Vincent Soriano ,Service of Infectious Diseases

Hospital Carlos III Madrid Spain

Documents

Recent Advances in the Management of Hiv Infection