Hair versus plasma concentrations as indicator of indinavir exposure in HIV-1-infected patients treated with indinavir/ritonavir combination.

Large intra-individual variability in plasma levels may limit the interest of therapeutic drug monitoring based on a single determination. Indinavir concentrations were determined both in plasma and hair samples, and correlated with concomitant plasma HIV-RNA in 43 HIV-infected patients. In multivariate analysis, significant association was found between HIV-RNA below 50 copies/ml and indinavir concentrations in hair but not in plasma, suggesting that hair concentrations gave more extensive information on drug exposure than a single plasma sample.

[Adherence intervention for HIV-infected patients receiving antiretroviral treatment. Implementation and initial assessment]. / Consultation d'observance pour des malades infectés par le VIH et traités par antirétroviraux dans un service de maladies infectieuses et tropicales. Mise en place et première évaluation.

OBJECTIVE: To describe the implementation and initial results of a specific educational and counseling intervention to examine and improve adherence to antiretroviral therapy (ARV) in HIV-infected patients. METHOD: Four patient profiles were defined: 1) discontinuation and 2) failure: patients with virological failure (defined as two consecutive viral loads>200 copies/mL) at ARV discontinuation or under treatment, both seen after the fact; 3) preparation: naive patients seen before starting treatment, and 4) reinforcement: patients in treatment seen for counseling to prevent virological failure. A clinical psychologist, nurse and hospital pharmacist jointly conducted the session. Data collected include standardized information about the characteristics of HIV infection and ARV regimens, and demographic, behavioral, social and cultural indicators. CD4 cell counts and HIV viral loads were recorded at D0, M1, M3, M9 and M12. The effectiveness of the adherence intervention was defined separately for each patient profile based on some combination of taking or restarting an ARV regimen, virological response, and M12 follow-up. RESULTS: The study included 139 patients between November 1998 and April 2000. The intervention was defined as effective in 50% and 40% of the discontinuation (n=26) and failure (n=61) patients respectively, 84% of those with preparation profile (n=37) and 93% (14/15) of reinforcement patients. Only undetectable HIV viral load at M3 was significantly associated with the effectiveness of the adherence intervention for all 4 profiles. The preventive interventions (preparation and reinforcement) were less effective in patients from outside Europe (p=0.013). CONCLUSION: The adherence intervention was more effective in preventing virological failure than in restoring ARV effectiveness among patients who had already experienced virological failure. It should therefore be proposed primarily before starting ARV, to prevent failure in treatment-naive patients, especially those from outside Europe.

Association of apolipoproteins C3 and E with metabolic changes in HIV-infected adults treated with a protease-inhibitor-containing antiretroviral therapy.

OBJECTIVE: To examine the relationship between plasma levels of apolipoproteins C3 (APOC3) and E (APOE) and the presence of lipid and carbohydrate metabolism abnormalities or clinical signs of lipodystrophy in HIV-1-infected patients started with a protease-inhibitor-containing antiretroviral therapy. METHODS: The Aproco (Antiproteases Cohort) Study enrolled 1,181 HIV-1-infected adults in 47 French healthcare centres from May 1997 to June 1998. From December 1998 through July 1999, the APROCO-Metabolic Complications (APROCO-MC) cross-sectional study was performed at the month 20 visit for those patients enrolled in 1997 and at the month 12 visit for those enrolled in 1998. The current analysis presents results from a subset of patients who had undergone additional tests to measure APOC3 and APOE in order to study their relationship with metabolic syndrome (n=157) and abnormal results in an oral glucose tolerance test (n=135). RESULTS: Increases in triglycerides and non-high-density lipoprotein (HDL) cholesterol were associated with significantly higher levels of APOC3, in both Lp B (lipoproteins containing apolipoprotein B) and Lp non-B (lipoproteins free of apolipoprotein B), and a significant higher level of APOE Lp B. APOC3 and APOC3 Lp non-B were increased when glucose metabolism abnormalities were more severe. The presence of a metabolic syndrome was associated with increased plasma APOC3, APOC3 Lp B and APOC3 Lp non-B levels. In a multiple regression analysis, high levels of APOC3 in Lp B and APOC3 Lp non-B were associated with the presence of clinical signs of lipodystrophy, even after adjustment for triglycerides and HDL-cholesterol levels. CONCLUSIONS: Lipid and/or glucose metabolism abnormalities in treated HIV-1-infected patients are associated with increased levels of APOC3 and, to a lesser extent, APOE plasma concentrations. Increased values are also related to clinical signs of insulin resistance and lipodystrophy.

The detection of non-adherence by self-administered questionnaires can be optimized by protease inhibitor plasma concentration determination.

Self-reported adherence and plasma protease inhibitor concentration (PPIC) were assessed in 642 HIV-infected patients at month 4 of a single protease inhibitor-containing regimen. PPIC was below the limit of quantification (LOQ) in 32% of non-adherent patients and in 8% of adherent patients. The relationship between non-adherence and a detectable HIV viral load was enhanced when adherent patients with PPIC below LOQ were considered to be non-adherent. PPIC combined with self-report may more reliably detect non-adherence.