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      Switch from unboosted protease inhibitor to a single-tablet regimen containing rilpivirine improves cholesterol and triglycerides

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          Abstract

          <p class="first" id="d3541483e198">This study aimed to evaluate the efficacy, tolerability and potential savings of combined antiretroviral therapy (cART) simplification from an unboosted protease inhibitor (PI) regimen with atazanavir or fosamprenavir to a single-tablet regimen (STR) based on rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) among HIV-1-infected patients with HIV-1 RNA &lt;50 copies/mL. This was a retrospective, multicentre, open-label, 12-week trial. Plasma HIV-1-RNA levels, CD4+ cell counts, cholesterol, triglycerides, bilirubin, glycaemia, creatinine and physical examination were performed at baseline and at scheduled follow-up. All patient costs were calculated and were estimated for 52 weeks of therapy. Fifty-one patients were enrolled [28 male (54.9%)]. At baseline, 30 patients (58.8%) were treated with FTC/TDF, 20 (39.2%) with abacavir/lamivudine and 1 (2.0%) with lamivudine/zidovudine. Thirty-three patients (64.7%) received atazanavir. All patients maintained HIV-RNA &lt;50 copies/mL; the median CD4+ cell count remained stable. Mean triglycerides decreased from 124 mg/dL (range, 39-625) at enrolment to 108.7 mg/dL (range, 39-561) at study end (P = 0.25). At baseline, mean cholesterol was 172.8 ± 38.1 mg/dL and decreased to 161.9 ± 38.6 mg/dL (P = 0.038); likewise, median total bilirubin decreased from 1.07 mg/dL (range, 0.2-4.7) to 0.6 mg/dL (range, 0.13-3.1) (P &lt;0.001). cART-related annual cost reduction with a STR was €3155.47 per patient (-24%). Non-cART patient management expenses were €402.68 vs. €299.10 for atazanavir or fosamprenavir and STR regimens, respectively. Switching to RPV/FTC/TDF from an unboosted PI in virologically suppressed HIV-infected patients is safe and is associated with a reduction in triglycerides, cholesterol and cART-related costs. </p>

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          • Record: found
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          Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance.

          HIV-1 protease-inhibitor treatments are associated with a syndrome of peripheral lipodystrophy, central adiposity, breast hypertrophy in women, hyperlipidaemia, and insulin resistance. The catalytic region of HIV-1 protease, to which protease inhibitors bind, has approximately 60% homology to regions within two proteins that regulate lipid metabolism: cytoplasmic retinoic-acid binding protein type 1 (CRABP-1) and low density lipoprotein-receptor-related protein (LRP). We hypothesise that protease inhibitors inhibit CRABP-1-modified, and cytochrome P450 3A-mediated synthesis of cis-9-retinoic acid, a key activator of the retinoid X receptor; and peroxisome proliferator activated receptor type gamma (PPAR-gamma) heterodimer, an adipocyte receptor that regulates peripheral adipocyte differentiation and apoptosis. Protease-inhibitor binding to LRP would impair hepatic chylomicron uptake and triglyceride clearance by the endothelial LRP-lipoprotein lipase complex. The resulting hyperlipidaemia contributes to central fat deposition (and in the breasts in the presence of oestrogen), insulin resistance, and, in susceptible individuals, type 2 diabetes. Understanding the syndrome's pathogenesis should lead to treatment strategies and to the design of protease inhibitors that do not cause this syndrome.
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            Metabolic disease in HIV infection.

            The treatment of metabolic disease is becoming an increasingly important component of the long-term management of patients with well controlled HIV on antiretroviral therapy (ART). Metabolic diseases probably develop at the intersection of traditional risk factors (such as obesity, tobacco use, and genetic predisposition) and HIV-specific and ART-specific contributors (including chronic inflammation and immune activation). This Review discusses present knowledge on adipose tissue dysfunction, insulin-glucose homoeostasis, lipid disturbances, and cardiovascular disease risk in people with HIV on ART. Although new antiretroviral drugs are believed to induce fewer short-term metabolic perturbations than do older drugs, the long-term effects of these drugs are not fully understood. Additionally, patients remain at increased risk of cardiovascular disease and other metabolic comorbidities. Research and treatment should focus on selection of ART that is both virologically effective and has minimum metabolic effects, minimisation of traditional risk factors for metabolic disease, and development of novel therapies to treat metabolic disease in patients with HIV, including use of anti-inflammatory and immunomodulatory drugs. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz: the effect of gender, race, and CYP2B6 polymorphism.

              To characterize the demographic and pharmacogenetic factors that influence interpatient variability in the plasma concentrations of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz. Data from all samples analyzed for efavirenz in our TDM service in 2002 and 2003 were reviewed. Information on gender, age, body weight, height, race, hormonal contraceptive use (in a subset of patients), and time between sampling and last intake was recorded. PCR-restriction fragment length polymorphism analysis was performed to detect the cytochrome P450 2B6 (CYP2B6) C1459T variant (present in CYP2B6*6 and CYP2B6*7) which is associated with low CYP2B6 activity. A total of 255 patients were included in this analysis. The median plasma efavirenz concentration was 2.50 (interquartile range: 1.85-3.55) mg l(-1). Eight patients (3.1%) were considered to have a subtherapeutic plasma concentration ( 4.0 mg l(-1)). Gender, time after last intake, and race were the only factors that were significantly related to plasma efavirenz concentration in a multivariate analysis. No influence was observed for body weight, hormonal contraceptive use, and the presence of the CYP2B6 C1459T polymorphism. Gender and race are important factors in determining interpatient variability in plasma efavirenz concentrations which were unaffected by the presence of the CYP2B6 C1459T polymorphism. Physicians should be particularly alert for signs of efavirenz-induced toxicity in females and non-Caucasian patients.
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                Author and article information

                Journal
                International Journal of Antimicrobial Agents
                International Journal of Antimicrobial Agents
                Elsevier BV
                09248579
                November 2016
                November 2016
                : 48
                : 5
                : 551-554
                Article
                10.1016/j.ijantimicag.2016.07.009
                27566908
                96b06616-7c10-4289-9b53-4cd83f18c721
                © 2016
                History

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