The African Eye Trust
HIV Treatment Information
Event
By Badru Male&Elijah
Amooti
April 15
Understanding HIV Treatment and
adherence.
Background
 HIV discovered within Gay communities in
San Francisco, USA in 1982 as HTLV1.
 1984 rediscovered in heterosexuals in
Central Africa
 In France, a scientist discovered that HIV
causes AIDS.
 1988 – Use of septrin to cure PCP and HIV
encephalopathy/Toxoplasmosis
 AZT Monotherapy
April 15
Understanding HIV Treatment and
adherence.
The UK HIV deaths Trend
 2006 - 5,505 new diagnoses of HIV
(about
50% acquired in Africa)
 84,730 Cumulative since 1982
(33% do not know they are HIV positive)
 40% People of African ethnicity
(about 24,000)
April 15
Understanding HIV Treatment and
adherence.
The UK HIV deaths Trend
 1995
-
1800 deaths
 2000
-
500 deaths
 2006
-
419 deaths (down by 15%)
 22,745 Cumulative deaths
April 15
Understanding HIV Treatment and
adherence.
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.
April 15
Understanding HIV Treatment and
adherence.
History of HIV Anti-Retroviral
Therapy (ART)
 Nucleoside analogues
– 1988, A drug called Zidovudine (AZT) used to
treat HIV infection.
– 1989, Videx (DdI)
– 1990, Hivid (DdI)
 Non-nucleoside analogues (1989)
(Nevirapine/ viramune)
April 15
Understanding HIV Treatment and
adherence.
History of HIV Anti-Retroviral
Therapy (ART)
 1995 Protease inhibitors (PI)
 Combination Therapy – Vancouver (1998)
 1999 – Tenofovir (Nucleotide analogue)
 2001- Entry inhibitor – T/20 (Fuzeon)
 2005 - Entry CCR5 receptors
April 15
Understanding HIV Treatment and
adherence.
Anti-Retro-Viral classes of drugs




Nucleoside analogues (NUKES)
Non-Nucleoside analogues (NON-NUKES)
Protease Inhibitors (PIs)
Entry/Fusion Inhibitors (FIs)
– CCR5 blockers
 Nucleotide analogues (Nukets)
 Intergrase inhibitors
April 15
Understanding HIV Treatment and
adherence.
Nukes
Non-nukes
Protease
Inhibitors
AZT
ddI
ddC
FTC
3TC
d4T
Abacavir
Tenofovir
(nt)
Combivir©
Kivexa ©
Trizivir ©
Truvada ©
Sustiva
Nevirapine
Delavirdine
TMC 125
Indinavir
T-20
Saquinavir CCR5
inhibitors
Lopinavir
Fosampren
avir
Ritonavir
Amprenavir
Kaletra ©
Nelfinavir
Atazanavir
Tipranavir
Duranavir
(TMC114)
April 15
Fusion/entry Integrase
Inhibitors
Inhibitors
Understanding HIV Treatment and
adherence.
GS-9137
MK-0518
Viral Enzymes
 Reverse Transcriptase
 Intergrase
 Protease
April 15
Understanding HIV Treatment and
adherence.
HIV Manifestation
H IVv irus
en try inh ibitors
C D4 cel l
pr ote ase in hib itors
nu ke s &
no n- nuk es
(N NRTIs)
April 15
Understanding HIV Treatment and
adherence.
Reverse
transcriptase
April 15
Understanding HIV Treatment and
adherence.
Genetic variability/mutation
Gene for
envelope
changes
Gene for
envelope
changes
Body makes
antibodies
Body makes
new antibodies
Antibodies cannot
recognise virus
April 15
Understanding HIV Treatment and
adherence.
New antibodies
cannot recognise
virus
How HIV infects T4 cells
VIRUS
T4 CELL CYTOPLASM
Enters host cell,
loses envelope
RT enzyme
Viral RNA
T4 cell
genome
RNA
DNA
copies of viral RNA
(messenger RNA)
Viral DNA
April 15
viral genome integrates
with T4 cell genome
New viruses bud
out of T4 cell
14
GROUP EXERCISE
 Assume that you are one of the viral
enzymes
 Pick a card of a drug that you consider your
enemy
 Place it in the right place
 Pick a friend from the other groups who will
help you fight the virus and explain
April 15
Understanding HIV Treatment and
adherence.
HIV Treatment issues







Starting treatment
Adherence
Side effects/Toxicity
Drug Concentration (IQ)
Drug Resistance
Changing treatment
Drug interactions
April 15
Understanding HIV Treatment and
adherence.
STARTING HIV TREATMENT
 Why start HIV treatment
 When to start HIV treatment
 What to start with
April 15
Understanding HIV Treatment and
adherence.
Viral load & CD4 after HIV-1 Infection
[without treatment]
Death
Seroconversion
Infection
Asymptomatic
Symptomatic AIDS
2 million
1000
CD4+
Cells/mm3
viral load
copies/mL
50
0
200
0
0
4-8 wks 2-12 mo
Up to 12 years
Time
April 15
Understanding HIV Treatment and
adherence.
2-3 years
ADHERENCE to ARVs





The meaning – (KMS=A)
What is non-adherence
Factors affecting adherence
Support needed for adherence
Outcomes of adherence
April 15
Understanding HIV Treatment and
adherence.
What is adherence?
 Knowledge
– How drugs work
– Why they work
– Why they may not work and consequences
 Memory
– Biopsychosocial issues
 Satisfaction
– Benefits, lifestyle, Side/effects/QOL
April 15
Understanding HIV Treatment and
adherence.
After HIV treatment (ARVs):
effect on CD4 and viral load
Start treatment
Viral load <50 copies/mL
2 million
1000
CD4+
cells/mm3
viral load (RNA)
copies/mL
50
0
200
< 50
copies/mL
0
0
+ 1-40+ years !!
1-12 yrs +1-6 mo
Chronic
Infection
April 15
Time
Understanding HIV Treatment and
adherence.
Drug levels and resistance.1
Taking drugs at the exact time makes sure that you keep above a minimum level
Increased risk of side effects
Drug
concentration
MEC
(Minimum
Effective
Concentration)
Increased risk of resistance
0
dose
April 15
dose
dose
Understanding HIV Treatment and
adherence.
dose
Side Effects/Toxicity
 Why it is better to know before starting.
 What are “side effects”
– Short term
– Long Term
 How to manage side effects
 The balance of benefits
April 15
Understanding HIV Treatment and
adherence.
Managing side effects
 Complimentary therapies
– Taichi
– Acupuncture
– Reflexology
– Shiatsu
– Yoga
 New fill for lipodystrophy
 Exercising for high LDL
April 15
Understanding HIV Treatment and
adherence.
Changing treatment combination




Why should some one change treatment
What should someone change to
When should someone change treatment
Why are consultants usually against change
April 15
Understanding HIV Treatment and
adherence.
Drug interactions







ARVs / ARVs
ARVs / Anelgesics
ARVs /Antibacterials
ARVs / Anticonvulsants
ARVs Antivirals
ARVs / Neoplastics
ARVs / Antiprotozoals
April 15
Understanding HIV Treatment and
adherence.
Drug interactions








ARvs / Sedatives
ARVs / Gastrointestinal agents
ARVs / Illicit recreational
ARVs / Immunosuppressants
ARVs / Steroids
ARVs / Herbals
ARvs / Beta blockers
ARVs / Antipsychotics
April 15
Understanding HIV Treatment and
adherence.
New Drugs
 PI – TMC114 (Darunavir, PREZISTA)
 600mg/boosted with 100mg Rit. BD
 NNRTI – TMC125
 CCR5 Inhibitors (in pipeline)
– Aplaviroc
– Vincriviroc
– Maraviroc
 CXCR4 Inhibitors (in pipeline)
 Integrase Inhibitors
April 15
Understanding HIV Treatment and
adherence.