Low Lopinavir Plasma or Hair Concentrations Explain Second-Line Protease Inhibitor Failures in a Resource-Limited Setting

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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.

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