Lopinavir Plasma Concentrations and Changes in Lipid Levels During Salvage Therapy with Lopinavir/Ritonavir-Containing Regimens

In order to evaluate the potential risk of nelfinavir (NFV) accumulation in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients with liver disease, we investigated the concentrations of NFV and M8, the active metabolite of NFV, in plasma HIV-positive (HIV؉) patients coinfected with HCV. A total of 119 HIV؉ subjects were included in our study: 67 HIV؉ patients, 32 HIV؉ and HCV-positive (HCV؉) patients without cirrhosis, and 20 HIV؉ and HCV؉ patients with cirrhosis. Most of the enrolled patients (chronically treated) were taking NFV at the standard dosage of 1,250 mg twice a day. To assay plasma NFV and M8 concentrations, patients underwent serial plasma samplings during the dosing interval at steady state. Plasma NFV and M8 concentrations were measured simultaneously by a high-performance liquid chromatography method with UV detection. The HIV؉ and HCV؉ patients with and without cirrhosis had significantly lower NFV oral clearances than the HIV؉ and HCV-negative individuals (28 and 58% lower, respectively; P < 0.05), which translated into higher areas under the concentration-time curves for cirrhotic and noncirrhotic patients. The NFV absorption rate was significantly lower in cirrhotic patients, resulting in a longer time to the maximum concentration in serum. The mean ratios of the M8 concentration/NFV concentration were significantly lower (P < 0.05) in HIV؉ and HCV؉ subjects with cirrhosis (0.06 ؎ 0.074) than in the subjects in the other two groups. The mean ratios for M8 and NFV were not statistically different between HIV؉ and HCV-negative patients (0.16 ؎ 0.13) and HIV؉ and HCV؉ patients without cirrhosis (0.24 ؎ 0.17), but the interpatient variability was high. Our results indicate that the pharmacokinetics of NFV and M8 are altered in HIV؉ and HCV؉ patients, especially those with liver cirrhosis. Therefore, there may be a role for therapeutic drug monitoring in individualizing the NFV dosage in HIV-HCV-coinfected patients.

show abstract

“…For some antiretroviral drugs, increased levels in plasma have been shown to be associated with increased toxicity (6,11,12,15).…”

mentioning

confidence: 99%

Clinical Pharmacokinetics of Nelfinavir and Its Metabolite M8 in Human Immunodeficiency Virus (HIV)-Positive and HIV-Hepatitis C Virus-Coinfected Subjects

Regazzi¹,

Maserati

Villani³

et al. 2005

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…They found a positive correlation between the percentage increase in triglycerides and LPV trough levels, but no correlation was found between LPV trough levels and the percentage of increase in cholesterol levels. 12 In a small population all patients with higher LPV trough (especially trough levels > 8 g/mL) levels were the ones at risk of dyslipidaemia [16,17]. Moreover, in a population of 142 ART-experienced patients high triglycerides were found in subjects with high LPV residual concentrations [11].…”

Section: Discussionmentioning

confidence: 99%

“…It is hypothesised that this dyslipidaemia is multifactorial and includes a direct effect of the PI and a more complex mechanism involveing immunologic, genetic and pharmacodynamic factors and HIV-infection itself [5,12,16,17,24]. To our knowledge this is the first prospective study analysing LPV levels with serum lipids in a cohort of only antiretroviral therapy-naive patients.…”

Section: Discussionmentioning

confidence: 99%

Lopinavir Plasma Concentrations and Serum Lipids in Therapy Naïve HIV-Patients: A Sub Analysis of the FREE Study

Hofstede¹,

Koopmans²,

Burger³

et al. 2012

View full text Add to dashboard Cite

Antiretroviral therapy in HIV patients is known for its negative effect on the cardiovascular system. One of the major adverse events in patients on lopinavir is increasing lipids. Hyperlipidaemia together with chronic inflammation by HIV-infection itself makes these patients prone for cardiovascular diseases.The purpose of this study (a sub study within the FREE-study) was to determine if higher plasma lopinavir (LPV) concentrations lead to increase of serum lipids. Plasma drug concentrations were analysed up to week 24 in a prospective cohort of HIV antiretroviral therapy naive patients who started on a regimen of zidovudine, lamivudine and ritonavir-boosted lopinavir (FREE study). Prospectively we measured plasma lopinavir concentrations from baseline to week 24 in 72 naive HIV-patients starting on lopinavir (59 males and 13 females). A total of 210 samples were analysed, with at least 2 samples in every patient. Mean LPV trough concentration was 4.3 mg/L (± 2.1). The median intra-subject variation in LPV level was 38% (range 4% -111%). Serum lipids were not correlated to LPV plasma concentrations possibly due to the wide intra-individual variability in LPV trough levels. Monitoring of plasma lopinavir and subsequent dose adjustment of LPV will not be useful to prevent hyperlipidaemia in HIV-patients treated with lopinavir.

show abstract

“…5,6 It has been suggested that concentrations of lopinavir below 1000 ng/mL are not adequate for suppression of wild-type virus, 8 and although studies have not provided a cut-off value, there have been positive correlations between lipid profiles 9 and liver enzyme elevation 10 and lopinavir pharmacokinetics. There is currently a lack of pharmacokinetic data in HIVinfected pregnant women and as such 'therapeutic' levels of lopinavir are based on data obtained from a Caucasian male cohort (University of Liverpool, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…Days on LPV/r at sampling 19 Hours since last dose 12 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) VL at trough sampling (copies/mL) 182 (40-252,000)…”

Section: Details Of Tdm Samples Median (Range)mentioning

confidence: 99%

Utility of therapeutic drug monitoring in the management of HIV-infected pregnant women in receipt of lopinavir

et al. 2011

View full text Add to dashboard Cite

SummaryThe pharmacokinetics of antiretroviral drugs in pregnancy is poorly understood. We reviewed the use of therapeutic drug monitoring (TDM) in clinical settings to document plasma concentrations of lopinavir during pregnancy and investigated how clinicians acted upon TDM results. A retrospective review was carried out of all HIV-infected pregnant women taking boosted lopinavir-based highly active antiretroviral therapy (HAART) at five National Health Service (NHS) centres in the UK between May 2004 and March 2007. Seventy-three women in receipt of lopinavir were identified, of whom 89% had plasma lopinavir concentrations above the suggested minimum recommended for wild-type HIV. Initial TDM results prompted dosage change in 10% and assessment of adherence and/or pharmacist review in 11%. TDM was repeated in 29%. TDM can play an important role in the clinical management of HIV-positive pregnant women, allowing informed dose modification and an alternative measure of adherence.

show abstract

Lopinavir Plasma Concentrations and Changes in Lipid Levels During Salvage Therapy with Lopinavir/Ritonavir-Containing Regimens

Cited by 77 publications

References 18 publications

Clinical Pharmacokinetics of Nelfinavir and Its Metabolite M8 in Human Immunodeficiency Virus (HIV)-Positive and HIV-Hepatitis C Virus-Coinfected Subjects

Clinical Pharmacokinetics of Nelfinavir and Its Metabolite M8 in Human Immunodeficiency Virus (HIV)-Positive and HIV-Hepatitis C Virus-Coinfected Subjects

Lopinavir Plasma Concentrations and Serum Lipids in Therapy Naïve HIV-Patients: A Sub Analysis of the FREE Study

Utility of therapeutic drug monitoring in the management of HIV-infected pregnant women in receipt of lopinavir

Contact Info

Product

Resources

About

Lopinavir Plasma Concentrations and Changes in Lipid Levels During Salvage Therapy with Lopinavir/Ritonavir-Containing Regimens

Cited by 77 publications

References 18 publications

Clinical Pharmacokinetics of Nelfinavir and Its Metabolite M8 in Human Immunodeficiency Virus (HIV)-Positive and HIV-Hepatitis C Virus-Coinfected Subjects

Clinical Pharmacokinetics of Nelfinavir and Its Metabolite M8 in Human Immunodeficiency Virus (HIV)-Positive and HIV-Hepatitis C Virus-Coinfected Subjects

Lopinavir Plasma Concentrations and Serum Lipids in Therapy Na&#239;ve HIV-Patients: A Sub Analysis of the FREE Study

Utility of therapeutic drug monitoring in the management of HIV-infected pregnant women in receipt of lopinavir

Contact Info

Product

Resources

About

Lopinavir Plasma Concentrations and Serum Lipids in Therapy Naïve HIV-Patients: A Sub Analysis of the FREE Study