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The African Eye TrustThe African Eye Trust HIV Treatment Information HIV Treatment Information

EventEventBy Badru Male&Elijah By Badru Male&Elijah

Amooti Amooti

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and adherence.and adherence.

BackgroundBackground

HIV discovered within Gay communities in HIV discovered within Gay communities in San Francisco, USA in 1982 as HTLV1.San Francisco, USA in 1982 as HTLV1.

1984 rediscovered in heterosexuals in 1984 rediscovered in heterosexuals in Central AfricaCentral Africa

In France, a scientist discovered that HIV In France, a scientist discovered that HIV causes AIDS.causes AIDS.

1988 – Use of septrin to cure PCP and HIV 1988 – Use of septrin to cure PCP and HIV encephalopathy/Toxoplasmosisencephalopathy/Toxoplasmosis

AZT MonotherapyAZT Monotherapy

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The UK HIV deaths TrendThe UK HIV deaths Trend

2006 - 5,505 new diagnoses of HIV 2006 - 5,505 new diagnoses of HIV ((about 50% acquired in Africaabout 50% acquired in Africa))

84,730 Cumulative since 198284,730 Cumulative since 1982((33% do not know they are HIV positive)33% do not know they are HIV positive)

40% People of African ethnicity 40% People of African ethnicity (about 24,000)(about 24,000)

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The UK HIV deaths TrendThe UK HIV deaths Trend

19951995-- 1800 deaths1800 deaths

20002000-- 500 deaths500 deaths

20062006-- 419 deaths 419 deaths (down by 15%)(down by 15%)

22,745 Cumulative deaths22,745 Cumulative deaths

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HIV and AIDS diagnoses and deaths in HIV infected individuals, UK reports to end December 2006

                                                                     

Numbers, particularly for recent years, will rise as further reports are received.

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History of HIV Anti-Retroviral History of HIV Anti-Retroviral Therapy (ART)Therapy (ART)

Nucleoside analoguesNucleoside analogues– 1988, A drug called Zidovudine (AZT) used to 1988, A drug called Zidovudine (AZT) used to

treat HIV infection.treat HIV infection.– 1989, Videx (DdI)1989, Videx (DdI)– 1990, Hivid (DdI)1990, Hivid (DdI)

Non-nucleoside analogues (1989)Non-nucleoside analogues (1989)

(Nevirapine/ viramune) (Nevirapine/ viramune)

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History of HIV Anti-Retroviral History of HIV Anti-Retroviral Therapy (ART)Therapy (ART)

1995 Protease inhibitors (PI)1995 Protease inhibitors (PI)

Combination Therapy – Vancouver (1998)Combination Therapy – Vancouver (1998)

1999 – Tenofovir (Nucleotide analogue)1999 – Tenofovir (Nucleotide analogue) 2001- Entry inhibitor – T/20 (Fuzeon)2001- Entry inhibitor – T/20 (Fuzeon) 2005 - Entry CCR5 receptors2005 - Entry CCR5 receptors

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Anti-Retro-Viral classes of drugsAnti-Retro-Viral classes of drugs

Nucleoside analogues (NUKES)Nucleoside analogues (NUKES) Non-Nucleoside analogues (NON-NUKES)Non-Nucleoside analogues (NON-NUKES) Protease Inhibitors (PIs)Protease Inhibitors (PIs) Entry/Fusion Inhibitors (FIs)Entry/Fusion Inhibitors (FIs)

– CCR5 blockersCCR5 blockers

Nucleotide analogues (Nukets)Nucleotide analogues (Nukets) Intergrase inhibitorsIntergrase inhibitors

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NukesNukes Non-nukesNon-nukes ProteaseProtease

InhibitorsInhibitors

Fusion/entry Fusion/entry

InhibitorsInhibitors

Integrase Integrase InhibitorsInhibitors

AZTAZT

ddIddI

ddCddC

FTCFTC

3TC3TC

d4Td4T

AbacavirAbacavir

Tenofovir Tenofovir (nt)(nt)

Combivir©Combivir©

Kivexa ©Kivexa ©

Trizivir ©Trizivir ©

Truvada ©Truvada ©

SustivaSustiva

NevirapineNevirapine

DelavirdineDelavirdine

TMC 125TMC 125

IndinavirIndinavir

SaquinavirSaquinavir

LopinavirLopinavir

FosamprenFosamprenaviravir

RitonavirRitonavir

AmprenavirAmprenavir

Kaletra ©Kaletra ©

NelfinavirNelfinavir

AtazanavirAtazanavir

TipranavirTipranavir

DuranavirDuranavir

(TMC114)(TMC114)

T-20T-20

CCR5 CCR5 inhibitorsinhibitors

GS-9137GS-9137

MK-0518MK-0518

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Viral EnzymesViral Enzymes

Reverse TranscriptaseReverse Transcriptase

IntergraseIntergrase

ProteaseProtease

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HIV ManifestationHIV Manifestation

protease inhibitors

entry inhibitors

nukes &non-nukes(NNRTIs)

HIV virus

CD4 cell

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Reverse transcriptas

e

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and adherence.and adherence.

 

Gene for envelope changes

Gene for envelope changes

Body makesantibodies

Antibodies cannotrecognise virus

Genetic variability/mutation

Body makesnew antibodies

New antibodies cannot recognise

virus

Apr 21, 2023Apr 21, 2023 1414

 

 

How HIV infects T4 cellsHow HIV infects T4 cells

 

VIRUS

New viruses bud out of T4 cell

T4 CELL CYTOPLASM

CD4 receptor molecule

Enters host cell, loses envelope

RT enzyme

Viral RNA

RNADNA

Viral DNA

viral genome integrates with T4 cell genome

copies of viral RNA (messenger RNA)

NUCLEUS

T4 cellgenome

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GROUP EXERCISEGROUP EXERCISE

Assume that you are one of the viral Assume that you are one of the viral enzymesenzymes

Pick a card of a drug that you consider your Pick a card of a drug that you consider your enemyenemy

Place it in the right placePlace it in the right place Pick a friend from the other groups who will Pick a friend from the other groups who will

help you fight the virus and explainhelp you fight the virus and explain

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HIV Treatment issuesHIV Treatment issues

Starting treatmentStarting treatment AdherenceAdherence Side effects/ToxicitySide effects/Toxicity Drug Concentration (IQ)Drug Concentration (IQ) Drug ResistanceDrug Resistance Changing treatmentChanging treatment Drug interactionsDrug interactions

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STARTING HIV TREATMENTSTARTING HIV TREATMENT

Why start HIV treatmentWhy start HIV treatment

When to start HIV treatmentWhen to start HIV treatment

What to start withWhat to start with

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4-8 wks Up to 12 years 2-3 years

Infection

Seroconversion

Asymptomatic Symptomatic AIDS

Death

1000

500

0

CD4+ Cells/mm3

viral load

200

2-12 mo

2 million

0

copies/mL

Viral load & CD4 after HIV-1 Infection[without treatment]

Time

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ADHERENCE to ARVsADHERENCE to ARVs

The meaning – (KMS=A)The meaning – (KMS=A) What is non-adherenceWhat is non-adherence Factors affecting adherenceFactors affecting adherence Support needed for adherenceSupport needed for adherence Outcomes of adherenceOutcomes of adherence

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What is adherence?What is adherence?

Knowledge Knowledge – How drugs workHow drugs work– Why they workWhy they work– Why they may not work and consequencesWhy they may not work and consequences

MemoryMemory– Biopsychosocial issuesBiopsychosocial issues

SatisfactionSatisfaction– Benefits, lifestyle, Side/effects/QOLBenefits, lifestyle, Side/effects/QOL

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After HIV treatment (ARVs): effect on CD4 and viral load

1-12 yrs +1-6 moChronicInfection

Start treatment

1000

500

0

CD4+ cells/mm3

viral load (RNA)copies/mL

200

2 million

0

+ 1-40+ years !!

< 50 copies/mL

Viral load <50 copies/mL

Time

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dose

Increased risk of side effects

0

Increased risk of resistance

dose dose dose

Taking drugs at the exact time makes sure that you keep above a minimum level

Drug levels and resistance.1

MEC(Minimum Effective Concentration)

Drug concentration

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Side Effects/ToxicitySide Effects/Toxicity

Why it is better to know before starting.Why it is better to know before starting. What are “side effects”What are “side effects”

– Short term Short term – Long TermLong Term

How to manage side effectsHow to manage side effects The balance of benefitsThe balance of benefits

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Managing side effectsManaging side effects

Complimentary therapiesComplimentary therapies– TaichiTaichi– AcupunctureAcupuncture– ReflexologyReflexology– ShiatsuShiatsu– YogaYoga

New fill for lipodystrophyNew fill for lipodystrophy Exercising for high LDLExercising for high LDL

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Changing treatment combinationChanging treatment combination

Why should some one change treatmentWhy should some one change treatment What should someone change toWhat should someone change to When should someone change treatmentWhen should someone change treatment Why are consultants usually against changeWhy are consultants usually against change

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Drug interactionsDrug interactions

ARVs / ARVsARVs / ARVs ARVs / AnelgesicsARVs / Anelgesics ARVs /AntibacterialsARVs /Antibacterials ARVs / AnticonvulsantsARVs / Anticonvulsants ARVs AntiviralsARVs Antivirals ARVs / NeoplasticsARVs / Neoplastics ARVs / AntiprotozoalsARVs / Antiprotozoals

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Drug interactionsDrug interactions

ARvs / SedativesARvs / Sedatives ARVs / Gastrointestinal agentsARVs / Gastrointestinal agents ARVs / Illicit recreationalARVs / Illicit recreational ARVs / ImmunosuppressantsARVs / Immunosuppressants ARVs / SteroidsARVs / Steroids ARVs / HerbalsARVs / Herbals ARvs / Beta blockers ARvs / Beta blockers ARVs / AntipsychoticsARVs / Antipsychotics

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New DrugsNew Drugs PI – TMC114 (Darunavir, PI – TMC114 (Darunavir, PREZISTA)PREZISTA)

600mg/boosted with 100mg Rit. BD600mg/boosted with 100mg Rit. BD

NNRTI – TMC125NNRTI – TMC125 CCR5 Inhibitors (in pipeline)CCR5 Inhibitors (in pipeline)

– AplavirocAplaviroc– VincrivirocVincriviroc– MaravirocMaraviroc

CXCR4 Inhibitors (in pipeline)CXCR4 Inhibitors (in pipeline) Integrase InhibitorsIntegrase Inhibitors