期刊
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
卷 56, 期 4, 页码 333-339出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0b013e31820dc0cc
关键词
hair concentration; lopinavir; medication adherence; plasma concentration; protease inhibitor resistance mutations; resource-limited settings
资金
- South African Department of Health
- United States National Institutes for Allergy and Infectious Disease (NIAID/NIH), Division of AIDS (DAIDS) [K23 AI 068582-01]
- European Developing Countries Clinical Trial Partnership Senior Fellowship Award [TA-08-40200-021]
- Wellcome Trust Southern Africa Consortium for Research Excellence [WT087537MA]
- NIH/FIC/HRSA/PEPFAR Medical Education Partnership Initiative (MEPI) [T84H21126-01-01]
- National Research Foundation, South Africa
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 mu g/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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