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HIV and AIDS
Table 2: ‘Matrix of Evidence’ for Therapeutic Drug Monitoring of Antiretroviral Drugs (www.delphicdiagnostics.com/tdmmatrix)
Routine Therapy Salvage Therapy Toxicity Liver Impairment Children Pregnancy Adherence
All PIs Optional (3/4) Optional (3/4) Recommended (3) Recommended (3) Recommended (3)
RCT: association
1,2
Drug concentrations Correlation between Review of evidence
12
Reviewed
13–18
RCT: no association
3–6
supplement resistance plasma drug
testing
7,8
concentration and
Association between toxicity
10
nIQ and virological No correlation
response
9
between plasma drug
concentration and
lipids
11
Amprenavir Optional (3/4) Recommended (3)
Association with IQs or Correlation between
drug concentrations
19–22
drug concentration
No association with and hepatic function
IQs or drug or hepatotoxicity
24,25
concentrations
23
Atazanavir Optional (3/4) Optional (3/4) Recommended (3) Recommended (3) Recommended (3)
Correlation between Association with Drug concentration No correlation Not susceptible to
drug concentration gIQ
30–32
associated with between drug low drug
and response
26,27
No association hyperbilirubinaemia concentration and concentrations
38
No correlation with C
30
min
and hepatic status
37
Susceptible to low
between drug No association genotype
26,29,31,34–36
drug concentrations
39
concentration and with gIQ
33
response
28,29
Indinavir Optional (3/4) Optional (3/4) Recommended (3) Recommended (3) Recommended (3) Recommended (3) Recommended (3)
RCT: association
1,2
Association with High drug Correlation between Variability and risk of Susceptible to low Reviewed
15,48,69–71
Drug concentration IQs or drug concentrations predict drug concentration underdosing
46,49,55,62–64
concentrations
65–67
predicts response or concentrations
51,52
renal toxicity
41,52–59
and hepatic function Case reports
68
development of High drug or hepatotoxicity
61
resistance and cut-offs concentrations
defined
40–45
predict toxicity
60
Children reviewed
46
RCT: drug
concentrations are
effective
47
Drug concentration
predicts response or
development of
resistance and cut-offs
defined
48
Children reviewed
49
Drug concentrations
do not predict
response
50
Lopinavir Optional (3/4) Optional (3/4) Recommended (3) Recommended (3) Recommended (3) Recommended (3)
Correlation between Association with High drug Correlation between Risk of Susceptible to low
drug concentration IQs or drug concentrations drug concentration underdosing
100–102
drug concentrations
103–108
and response
72–75
concentrations
22,73,77–84
correlate with and hepatic function
No correlation lipodystrophy
85
or hepatotoxicity
37,95
between drug High drug No correlation
concentration and concentrations between drug
response
76
correlate with concentration and
lipids
86–88
hepatic function or
High drug hepatotoxicity
96–99
concentrations
correlate with
cholestasis
89
No correlation with
lipids
90–92
No correlation with
gastrointestinal
toxicity
93
Higher rate of diarrhoea
may correlate with
C
94
max
28 EUROPEAN INFECTIOUS DISEASE
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