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Introduction:
Non nucleoside reverse transcriptase inhibitors (NNRTIs) are
currently used in combination with other antiretrovirals for
treatment of HIV infection. Few data suggest that their plasma
trough concentration (Cres) could be related to clinical
efficacy and therefore, target values have been proposed for TDM
purpose.
Methods:
447 NNRTIs plasma Cres determinations (EFV = 328, NVP = 119)
measured during a 2 years follow up (01/2000 to 09/2002) were
recorded and correlated to viral load (VL), genotype (K103N and
Y181C mutations) and drugs related side effects (neurologic for
EFV, hepatic for NVP). All the patients have received at least 5
lines of treatment but some of them were NNRTI naïve while the
others were NNRTI pre-treated.
Results:
30 % of the trough levels were under the French ANRS target
interval values [i.e. 1.1 - 5 mg/l (EFV) and 3 – 8 mg/l (NVP)],
while 2.5% were above them. In NNRTIs naïve patients receiving
EFV, those showing an undetectable VL or the highest VL decrease
exhibit the higher Cres (1.77 ± 1.12 vs 1.49± 0.77 mg/l,
p<0.05). No such difference was found in the pre-treated group.
Moreover, among pre-treated patients receiving EFV and
experiencing virological failure Cres was higher than the naïve
group (2.30 ± 2.11 vs 1.49 ± 0.77 mg/l, p<0.03). The K103N
and/or Y181C mutations were more frequent in pre-treated group
than in naïve group (38% vs 3%, p<0.02), and, among the patients
treated with NVP, those showing K103N or Y181C mutations have
Cres behind the target value. Finally, the adverse events were
infrequent (3% of the patients) whatever the NNRTI.
Conclusion:
About 1/3 of the patients dosed with standard of care appears to
be underdosed. Even, it is obvious that the best way to optimise
the dosage regimen should be to take into account all the drugs
used, we demonstrated that TDM of NNRTIs could be of interest in
preventing virological failure, mostly in NNRTIs naïve patients.
Moreover, the actually recommended Cres for these patients is
probably insufficient for heavily pre-treated patients. |
