THE IMPORTANCE OF ADHERENCE

Improving the success of

drug treatment
 What is adherence ?

Adherence means that therapy is taken

according to prescribing instructions
i.e. the recommended dose, at the
recommended time and in the
recommended way
Patient Involvement

Adherence requires the active

participation of the patient
Adherence is likely to be greatest
when the patient is involved in
his or her treatment decisions
 Adherence in chronic disease
Hypertension
Bronchial Asthma
Diabetes Mellitus

Only 50% of patients remain highly

adherent to treatment over time
 Adherence: The Greatest Barrier to Successful
Antiretroviral Therapy

Potent regimen Host factors

Delay in
Adherence disease
progression

Pharmacokinetics Inhibition of
Absorption Systemic Intracellular
concentration concentration viral
Metabolism replication
Excretion

Viral resistance
Viral virulence
Adapted from Friedland GH, Williams A. AIDS. 1999.
Examples of non-adherence

Missed dose
Delayed dose
Failing to follow guidelines
(e.g. with food)
Experimenting with dosing
Drug holidays
Stopping ART even briefly….
Rapid rebound of viral load
Selection of drug resistant HIV strains
Significant damage to the immune system
Danger of transmission of resistant virus
Second and third line options are exhausted earlier
Loss of therapy benefits – waste of resources for
the patient
Subsequent regimens are more expensive
More lab tests and clinic visits are required
 Correlation Between Adherence and Virologic Failure p = 0.00001]

100
% (n) Patients with Virologic Failure
94
75 15/16
(6/8)
75
50
3/6
50 36
(4/11)

19
(3/16)
25

0
>95% 90-95 80-90 70-80 <70

%ofPatientsAdherent-MEMScaps data
→ >95% adherence is required to achieve undetectable
viral loads in 80% of patients
D Paterson et al. 6th Conference on Retroviruses and OIs, Chicago, February 1999 Abstract 092
 Patient factors
Active substance Expectations about efficacy
and risk about side effects
abuse
Concomitant illnesses
Male sex No change in health-status
Youth Education about disease
and its medication
Psychological distress
Perception about
illness

Clin Inf Dis 2000(Suppl 2):S171-6

 Medication-related factors
Dose frequency > 2 times a day
Pill burden
Food requirements
Type of drug
Inability to take medication when away
from home
Side effects
 Frequency of Dosing is Critical to Maintain
Adherence in Other Chronic Disease Areas

Regimen Adherence
Once a day 73%
Twice a day 70%
Three times daily 52%
Four times daily 42%

→ Once a day and twice a day regimens are

associated with significantly better
adherence
Greenberg RN. Clinical Therapeutics 1984; 6(5):
 Plot of Virologic Response by Pill
Burden (r=-0.61, p=0.0056)
100
Percent < 50 at 48 Weeks

PI
80
NRTI
60 NNRTI

40

20

0
5 10 15 20

Number of Antiretroviral Pills Per Day

Size of symbol is directly proportional to weight of the data point in the
analysis.

Bartlett J- 7th CROI; 2000; San Francisco. Abs. 519.

 Patients and Doctors Perspective on
Adherence Difficulties

National survey (1999) : 1599 patients, 138 AIDS physicians

Patients Doctors
Number of pills
Number of daily intakes
Pills size
Side-effects
Need to take drugs while fasting
Need to take drugs with food
Need for long-life treatment
Integration of ART in everyday life

AIDES, Fédération Nationale, Nov 1999

%
0 20 40 60 80
Raffi, F. 2nd International HIV/AIDS Colloquium, Guadalajara, Mexico, May 18-19, 2000.
 Barriers to adherence identified by
patients
Rank Barrier Score
1 Difficulty remembering 85
morning dose 4
afternoon dose 61
evening dose 26
2 Inconvenient timing 54
3 Difficulty scheduling around food 38
4 Adverse effects 22
5 Size and no of medications 15
6 storage specifications 10
7 Hydration requiements with IDV 4
8 Difficulty with discreet administration 3

Ann Phamacother 2000;34:703-9

Strategies to improve adherence
Simpler regimens
Easy incorporation into patient lifestyle
Few, compact, easy to swallow tablets
Dosing not affected by food/fluid intake
Fixed dose formulations
Counseling
Patient reminders
Patient involvement in treatment decisions
Using family members as support
Attributes of an ‘ideal’ ART regimen
Proven potency
Durability of viral suppression
Penetration into other body compartments
Few pills and minimal doses
No scheduling around food
Minimal/manageable long term toxicity
Few or no drug interactions
Cheap
Easy to explain to patients
 Advantages of fixed dose
combinations and kits

Ensures that all 3 drugs are taken and

efficacy is not compromised
Compliance – dosage is simplified
Economy
World’s first Triomune-30/40
World’s first Triomune: Dosage
Triomune –30 : For patients < 60 kg
Lamivudine 150 mg + Stavudine 30 mg + Nevirapine 200
mg

Triomune-40 : For patients > 60 kg

Lamivudine 150 mg + Stavudine 40 mg + Nevirapine 200
mg

1 tablet twice daily irrespective of meals

World’s first
Triomune: Warning
Not to be used for initiating therapy
Triomune should be begun only after
patients have received lamivudine 150 mg
b.i.d, stavudine 30/40 mg b.i.d (Lamivir-S)
and nevirapine 200 mg o.d (Nevimune) for
14 days and have demonstrated adequate
tolerability
World’s first Duovir-N
World’s first
Duovir-N
1 tablet twice daily irrespective of meals
Not to be used for initiating therapy
Duovir-N should be begun only after patients
have received lamivudine 150 mg b.i.d,
zidovudine 300 mg b.i.d (Duovir) and
nevirapine 200 mg o.d (Nevimune) for 14 days,
and have demonstrated adequate tolerability
Viraday - One pill once a day
World’s first Duovir-E kit
 Odivir Kit
World’s first 3 pills once daily
Lamivir SE Kit
World’s first Triomune Baby/Junior
World’s first
Triomune Baby/Junior
Currently, inadequate treatment options for
children with HIV
d4T + 3TC + NVP – recommended regimen
World’s first 3-in-1 FDC for children
Small tablet, easy to swallow
Dispersible and scored, in 2 strengths
Simplified dosing according to weight bands