Stavudine plasma concentrations and lipoatrophy.
OBJECTIVE
The objective of this study was to determine the correlation between plasma stavudine concentrations and lipoatrophy (LA), one of the major adverse events in patients on stavudine and one of the major reasons to discontinue stavudine.


METHODS
Plasma drug concentrations were retrospectively analysed in patients who were on a stavudine-containing regimen for at least 12 months. We defined two groups of patients: 21 patients with LA and 15 patients without LA or other stavudine-related side effects (i.e. neuropathy).


RESULTS
We analysed stavudine concentrations in 212 plasma samples: 87 in the control group and 125 in the LA group, with a mean of four plasma samples per person (at least two a year). Demographics were comparable in LA patients and controls, except the duration of stavudine use, which was longer in the LA group: 55 versus 42 months in the control group. Overall, LA patients had higher drug exposure to stavudine when compared with the controls, and this was seen in the geometric concentration ratios (CRs), which were 0.978 and 0.741, respectively (P = 0.04), and also a higher percentage of CR values >1.0, representing a drug concentration above the normal population curve (46% versus 23%, P = 0.02). In addition, the duration of stavudine therapy was independently associated with LA (P = 0.05). In the multivariate analysis, both duration of stavudine (P = 0.05) and CR > 1.0 (P = 0.02) were independently correlated with LA.


CONCLUSIONS
Monitoring of plasma stavudine concentrations can be useful to prevent stavudine-related LA.
ter Hofstede
Hadewych J M
HJ
Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. h.terhofstede@aig.umcn.nl
Koopmans
Peter P
PP
Burger
David M
DM
D000328:Adult; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008060:Lipodystrophy / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010949:Plasma / Q000737:chemistry*; D012189:Retrospective Studies; D018119:Stavudine / Q000009:adverse effects* / Q000097:blood* / Q000627:therapeutic use; D013997:Time Factors
D018119:Stavudine