Transcript HAART HIV project

When Less is More:
Transmission of Drug-Resistant
HIV in Canada
STIRRHS Conference
Montreal, Quebec
June 3, 2006
Why do this project?
• HIV challenge
• 5000 new cases annually
• Living long with HIV through HAART
Who is Spreading HIV ?
333 HIV Positive Patients
75/333 (23%)
Unprotected Intercourse
18/75 (24%)
Drug Resistant HIV
155/191 Partners
HIV Negative
So what’s the problem?
• HAART regimen is demanding
• Adherence must be >95%
• 57-77% of patients cannot adhere
optimally
• At 80% adherence drug resistance
develops
Barriers to Reducing Spread
1. Drugs are not “user-friendly”
2. Adherence is not optimal
3. Not all sex is safe
Hypothesis
• The spread of drug-resistant HIV virus can
be reduced by redesigning the strategy of
treatment targeted towards one of these
three pillars:
– Improving adherence
– Reducing the development of drug-resistance
– Reducing risk sexual and drugs-associated
behaviour
Objectives
This collaborative group will use a
transdisciplinary approach to improve
patient adherence to HAART and prevent
the spread of drug-resistant HIV by:
– Optimizing drug combinations/delivery
– Alleviating side effects to treatment
– Identifying factors associated with decreased
adherence specific to the Canadian
population
– Furthering “safe-sex” techniques
Objectives
ADHERENCE
TO
HAART
Objective 1
Influence
adherence
Objective 2
Influence
development of
resistance
Objective 3
Modify
risk behaviour
RISK
BEHAVIOUR
DEVELOPMENT OF
RESISTANCE
SPREAD OF
RESISTANT HIV
Objective 1: Adherence
a. Understand the problems of adherence to
HAART
b. Design, implement and evaluate a computerbased tool designed to improve management
of drug side effects
c. To modify the influence of side-effects of
therapy on drug adherence by designing
alternative drug delivery methods
Design (1)
• Understand the problem of adherence and
barriers related to HAART
• 1st year: Qualitative study: understand
point of view, motivation, psychological
concerns of patient and health
professionals, study of barriers to therapy
adherence (implementation, analysis)
Design (2)
• Development of an intervention
• Information-motivation-behavioural skills
model
• Specific intervention…
Design (3)
• Stratify in three groups: <80%, 80-95%
and >95% adherence to HAART
• Evaluation of intervention
– RCT
Primary Health Outcome Measures
Level of Adherence
Level of Drug-resistant HIV
Number of New Cases of Drug-Resistant
HIV
The Problem of Side Effects
• Cluster randomized, controlled trial
• HIV positive patients
• Clinic waiting rooms
The Problem of Side Effects
• Half of treatment centers will complete a
computer based survey
– Length of illness
– Adherence to treatment
– Side effect profile
– Risky sexual behavior
The Problem of Side Effects
• The computer will provide a print out of the
side effect profile
• Pharmacists will review the profile and
determine the likely causal agents
• Physicians will use the information to give
patients coping strategies and/or
prescriptions to abate side effects
The Problem of Side Effects
• Additionally, the computer will provide the
patient with information regarding
adherence and risk of drug resistant HIV
as well as decreasing transmission as the
survey is being completed
• Issues can then be further discussed with
the clinician
The Problem of Side Effects
At the completion of the study, we will
compare the control and intervention
groups to determine if there is a difference
in adherence between the groups
HIV INFECTION
HAART
NON-ADHERENCE
Complex regimen
Toxicity
RESISTANCE
Mechanisms of resistance
SPREAD
The aims of this project are
1. to simplify drug regimen by developing
new drug delivery methods
2. reduce toxicity by using newer agents
Complex Regimen
Three classes of drugs
A, B & C : A1,B1 and C1
Some in empty stomach / others in full stomach
Multiple pills, large size
Toxicity
New drug delivery methods such as
Transdermal patch
New combination of drugs – for example A1, B2
and C3
Methods to Improve Adherence
• New Drug Delivery Methods
• Transdermal patch
• Reduce toxicity
• Combination of drugs A1, B2 and C3
New Drug Delivery Methods
Study Design
Randomized control trial
Participants : non-adherent patients
The usual oral regimen (n=50)
Transdermal patch (n=50)
Adherent patients (>95%) (n=50)
For three months
Outcomes:
Drug concentrations
Viral load
CD4 counts
Patient compliance – side effects
New Drugs
Patients will be randomized to receive either
1. A1, B1, C1
2. A1, B2, C3
As transdermal patches
Outcomes:
Side effect profile
Viral load
CD4 counts
Objective 2
Mechanisms of Resistance
• Non- adherence (50%) patients
• Mutations in viral enzymes & proteins
• The aim of this study will be to elucidate
the mechanisms of drug resistance to
HAART
• Study Design
HIV will be cultured from non-adherent
(50%) patients
• Mutations in the viral enzyme and proteins
to be determined using DNA
• 3-D structure of the proteins determined
• In vitro cell culture studies
• to compare the efficacy of the usual and
the new combinations of drugs
• To compare the development of drug
resistance
Outcome:
Drug resistance – viral counts
• Experimental Design
• Cultured HIV will be incubated with
increasing concentrations (1uM to 1mM) of
either the usual or new combinations of
drugs for 24 hours to 72h
• Different regimens of failing drug adherence
• At the end of treatment period
perform – viral counts and examine for
mutations in HIV
Bench to Bedside
• RCT to compare drug resistance in the
usual and the new combination of drugs
• Newly identified HIV patients will be
randomized to receive either
• Usual drug combination or the new drug
combinations for 1 year
• Examine viral load, CD4 counts, mutations
in HIV
Objective 3:
Reduce risk behaviour
• Assessment of risk behaviour
– Survey
– Correlate risk-behaviour with adherence, viral load
and resistance
• Intervention
– Educate – show movie, talk to clinic nurse, doctor,
educate doctor
– Provide needles and condoms
• Test intervention with questionnaire
• Evaluate intervention efficiency
Objective 3:
Reduce risk behaviour
• Objective: to reduce spread of HIV by risk
behaviour
• Research design: case-control,
prospective
• Primary measure of health outcome: risk
behaviour after intervention
Team members and their
contributions
Members
• HIV-positive patients and
partners
• Doctors
• Psychologists
• Anthropologist/
Sociologist
• Basic scientist/
pharmacologist, virologist
• Epidemiologist
• Computerperson
Contribution
To adhere or not to adhere
and behave
Clinical perception
Theoretical concepts
Understand determinant
factors
Resistance development
studies bghjewlfbyw
Obvious
Software design
The real team members
•
•
•
•
•
•
Nils Chaillet
Li Chen
Barbra de Vrijer
Pia Elustondo
Laura Gaudet
Sownd
Sankaralingam
• Dr William Fisher
• Dr Robert Platt
• Dr Lise Goulet