Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting.
BACKGROUND
In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure.


METHODS
We conducted a cross-sectional survey to investigate the aetiology of virologic failure in 2 public health antiretroviral clinics in South Africa documenting the prevalence of virologic failure (HIV RNA load >500 copies/mL) and genotypic antiretroviral resistance; and lopinavir hair and plasma concentrations in a nested case-control study.


RESULTS
Ninety-three patients treated with a second-line regimen including lopinavir boosted with ritonavir were included, of whom 50 (25 cases, with virologic failure and 25 controls) were included in a nested case control study. Of 93 patients, 37 (40%) had virological failure, only 2 of them had had major PI mutations. The negative predictive values: probability of failure with lopinavir plasma concentration >1 µg/mL or hair concentrations >3.63 ng/mg for virologic failure were 86% and 89%, and positive predictive values of low concentrations 73% and 79%, respectively, whereas all virologic failures with HIV RNA loads above 1000 copies per milliliter, of patients without PI resistance, could be explained by either having a low lopinavir concentration in plasma or hair.


CONCLUSIONS
Most patients who fail a lopinavir/ritonavir regimen, in our setting, have poor lopinavir exposure. A threshold plasma lopinavir concentration (indicating recent lopinavir/ritonavir use) and/or hair concentration (indicating longer term lopinavir exposure) are valuable in determining the aetiology of virologic failure and identifying patients in need of adherence counselling or resistance testing.
Division of Medical Virology, Department of Pathology, NHLS Tygerberg and Stellenbosch University, Tygerberg, South Africa. guvz@sun.ac.za
Gert Uves
GU
van Zyl
Thijs E
TE
van Mens
Helen
H
McIlleron
Michele
M
Zeier
Jean B
JB
Nachega
Eric
E
Decloedt
Carolina
C
Malavazzi
Peter
P
Smith
Yong
Y
Huang
Lize
L
van der Merwe
Monica
M
Gandhi
Gary
G
Maartens
D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006197:Hair / Q000737:chemistry*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D011744:Pyrimidinones / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D013019:South Africa; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir
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