Dyslipidaemia after switch to tenofovir alafenamide (TAF)-based cART regimens in a cohort of HIV-positive patients: what clinical relevance?

OBJECTIVES: Switching from tenofovir (TDF) to tenofovir alafenamide (TAF) affects lipid profile. The aim of this study was to evaluate whether this results in an increased frequency of patients with low-density lipoprotein (LDL) above their cardiovascular-related target. METHODS: All HIV patients switching from TDF to TAF, with no changes of the anchor drug, and with plasma lipids available within 6 months before and after the switch, were included. Demographic, HIV-related parameters, cardiovascular (CV) risk factors and lipid profile on both TDF and TAF were collected. The CV risk score and the relative target of LDL for each patient were calculated according to 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for the management of dyslipidaemias. Modifications in lipid profiles and in the prevalence of patients with LDL above their CV-related target were evaluated after switch to TAF. RESULTS: Overall, 221 HIV patients were included, according to CV risk: 55% at low risk, 34% at moderate risk, and 11% at high/very high risk. By analysing lipid profiles according to CV risk, 38% of patients on TDF had LDL above their CV target; this prevalence increases to 60% after switching to TAF (P < 0.0001). The presence of cobicistat in the combination antiretroviral therapy (cART) regimen was associated with an increased risk of LDL above the CV-related target after switch to TAF [adjusted odds ratio (aOR) = 2.4, 95% confidence interval (CI): 1-5.1], P = 0.03) and with an increased prescription of lifestyle/therapeutic intervention (OR = 3.0, 95% CI: 1.7-5.3, P < 0.0001). DISCUSSION: Switching from TDF to TAF affects lipid parameters, and data from real life suggest a clinical relevance of this worsening that often leads clinicians to implement lifestyle/therapeutic interventions.

Estudo fitoquímico e análise mutagênica das folhas e inflorescências de Erythrina mulungu (Mart. ex Benth. ) através do teste de micronúcleo em roedores / Phytochemical and mutagenic analysis of leaves and inflorescences of Erythrina mulungu (Mart. Ex Benth. ) through micronucleus test in rodents

Este trabalho teve como objetivo investigar a composição química, estabelecer a dose letal média (DL50) e avaliar os potenciais efeitos mutagênicos do extrato hidroalcoólico de folhas e inflorescências de Erythrina mulungu Mart. ex Benth por meio do teste de micronúcleo em medula óssea de camundongos. Os ensaios fitoquímicos foram realizados através de reações preliminares com mudança de coloração e/ou formação de precipitado; a DL50, por meio da administração intraperitoneal de três concentrações dos extratos, avaliando-se o número de óbitos após 48 horas e o teste de micronúcleo foi feito por meio do método do esfregaço, após exposição dos animais a cinco dias de tratamento. Os resultados fitoquímicos demonstraram presença de açúcares redutores, fenóis e taninos, proteínas e aminoácidos, flavonóides, alcalóides, depsídeos e depsidonas e derivados de cumarina em ambos os órgãos; saponinas espumídicas e esteróides e triterpenóides nas folhas e glicosídeos cardiotônicos e antraquinônicos e alcalóides nas inflorescências. Para a DL50 a folha demonstrou-se atóxica e a inflorescência moderadamente tóxica. Para o teste de micronúcleo, os resultados indicaram ausência de citotoxicidade e genotoxicidade dose-dependente para as folhas e independente da dose para as inflorescências. Assim, esses resultados sugerem que a planta, nas condições analisadas, possui potencial para induzir danos ao DNA.

This study aimed to investigate the chemical composition, to establish the mean lethal dose (LD50) and to assess the potential mutagenic effects of hydroalcoholic extract of leaves and inflorescences of Erythrina mulungu Mart. ex Benth by using micronucleus test in bone marrow of mice. Phytochemical assays were carried out through preliminary reactions with color change and/or precipitate formation; the LD50 was obtained by intraperitoneal administration of three concentrations of the extracts, assessing the number of deaths after 48 hours, and the micronucleus test was done by the smear method, after exposure of animals to five days of treatment. Phytochemical results showed the presence of reducing sugars, phenols and tannins, proteins and amino acids, flavonoids, alkaloids, depsides, depsidones and coumarin derivatives in both organs; foaming and steroidal saponins and triterpenes in the leaves and cardiotonic and anthraquinonic glycosides and alkaloids in the inflorescences. Considering the LD50, the leaf was atoxic and the inflorescence was moderately toxic. As regards the micronucleus test, results indicated absence of cytotoxicity while genotoxicity was dose-dependent for leaves and dose-independent for inflorescences. Thus, these results suggest that the plant, under the tested conditions, has the potential to induce damages to the DNA.

Impact of HAART on liver histology of HIV/HCV coinfected patients.

The impact of HAART on the progression of HCV related liver disease is controversial. This retrospective study compares the grading and staging of chronic viral hepatitis in HIV/HCV coinfected subjects treated or not with antiretroviral therapy (ART) including protease inibithors (PI). The liver histology of 44 HIV/HCV coinfected patients on ART for more than 12 months, 26 coinfected patients naïve for ART and 31 HCV monoinfected patients were analysed by the Ishak score. None of the multivariate models calculated to test if liver histopathology (Ishak grading or staging) between HIV/HCV coinfected patients versus HCV monoinfected or antiretroviral-treated versus untreated HIV+ subjects showed any statistical difference. No significant difference between grading and staging was evidenced either in PI treated subjects versus patients on ART without PI.

Acute self-limiting hepatitis C after possible sexual exposure: sequence analysis of the E-2 region of the infected patient and sexual partner.

We describe a case of symptomatic acute infection with HCV in a woman whose sexual partner had chronic hepatitis C. The patient cleared HCV RNA 8 weeks after the onset of acute hepatitis and was found to be persistently HCV-RNA negative during 90 weeks of follow-up. Part of the E-2 region of HCV was directly sequenced in the patient and her sexual partner. Four local controls with subtype-1a infection and 9 1a isolates obtained from GenBank were analyzed. The average nucleotide divergence between the sequences of the infected patient and her sexual partner was 5.1%, compared with an average nucleotide divergence of 19.4% (range 16.6-21.8%) between the sequences of the patient and those of controls. Comparison of the phylogenetic trees in the partial E-2 region showed that the sequence of the patient was closely related to that of her sexual partner. Our findings suggest that the infection was transmitted to the patient from her sexual partner. The resolution of acute hepatitis C in this case was probably related to the host rather than to intrinsic characteristics of the HCV genome.

Singlet oxygen mediated degradation of Klason lignin.

After some results concerning photochemical generated singlet oxygen on lignins from steam explosion, the reactions of chemically generated singlet oxygen with Klason lignins from pine and beech are described. Singlet oxygen was produced through the reaction of hydrogen peroxide with sodium hypochlorite. The degradation of lignin was followed by uv spectroscopy and gel permeation chromatography. Extensive degradation of the lignins was observed when 20 mg of Klason lignin was treated with 1 ml of 30% hydrogen peroxide and 8.56 ml of 1.093 M sodium hypochlorite. In the uv spectra registered after the treatment with singlet oxygen the absorptions typical of lignin (210-220 nm and 250-280 nm) were completely absent. The gpc analysis of lignin after a treatment with 0.1 ml of hydrogen peroxide and 0.86 ml of sodium hypochlorite showed a clear reduction of signals due to the lignin and a shift to lower molecular weight. The potential use of this procedure in the bleaching procedure was tested by using recycled paper. A maximum reduction of 51% in the amount of lignin in this paper was observed.

Use of polymerase chain reaction assays of aqueous humor in the differential diagnosis of retinitis in patients infected with human immunodeficiency virus.

We performed polymerase chain reaction (PCR) for detection of cytomegalovirus (CMV), varicella-zoster virus (VZV), herpes simplex virus (HSV), and Toxoplasma gondii DNA in aqueous humor from 15 patients who were infected with human immunodeficiency virus (HIV) and who had retinitis of unclear origin; these patients were selected from among 820 patients evaluated by ophthalmoscopic examination. On the basis of the final response to treatment, CMV, VZV, and T. gondii retinitis was diagnosed in 5, 2, and 4 of the 15 patients, respectively. No final etiologic diagnosis was reached for four patients. All 5 patients with CMV retinitis were CMV DNA-positive. 1 of 2 patients with VZV retinopathy were VZV DNA-positive, and 3 of 4 patients with T. gondii retinitis were T. gondii DNA-positive. All PCR assays of aqueous humor from the four patients without infectious retinitis were negative. PCR assay of aqueous humor is helpful in the etiologic diagnosis of retinitis of unclear origin in HIV-infected patients.

Filgrastim to treat neutropenia and support myelosuppressive medication dosing in HIV infection. G-CSF 92105 Study Group.

BACKGROUND: Patients with HIV infection frequently experience disease or treatment-related myelosuppression leading to neutropenia. Neutropenia often leads to dose-reduction or discontinuation of important myelosuppressive therapy. OBJECTIVE: To examine the efficacy and safety of filgrastim for reversing neutropenia and determine the effect of this on use of myelosuppressive medications. DESIGN: Open-label, non-comparative, multicentre study in 200 HIV-positive patients with neutropenia [absolute neutrophil count (ANC) < 1.0 x 10(9)/l]. Filgrastim was started at 1 microgram/kg/day subcutaneously for 28 days. This initial treatment phase was followed by a maintenance phase, using 300 micrograms on 1-7 days/week. In both phases the dose of filgrastim was adjusted to achieve an ANC of 2-5 x 10(9)/l. RESULTS: Filgrastim reversed neutropenia in 98% of patients (ANC > or = 2 x 10(9)/l), with a median time to reversal of 2 days (range 1-16) and a median dose of 1 microgram/kg/day (range 0.5-10). Most patients (96%) achieved reversal of neutropenia with a filgrastim dose of < or = 300 micrograms/day (< or = 1 vial/day). Normal ANCs were then maintained with a median of 1 microgram/kg/day (range 0.22-10.6) during the treatment phase and 3 x 300 micrograms vials/week (range 1-7) during the maintenance phase. Ganciclovir, zidovudine, co-trimoxazole and pyrimethamine were the drugs most frequently considered to be causing neutropenia, and 83% of patients received one or more of these in the study. Filgrastim allowed > 80% of patients to increase or maintain dose-levels of these four medications or add them to their therapy. The number of these four medications received per patient increased by > 20% during filgrastim therapy. Filgrastim was well tolerated. CD4, CD8 and total lymphocyte counts all increased slightly, and there was no difference in HIV-1 p24 antigen levels. CONCLUSION: Filgrastim rapidly reverses neutropenia and maintains normal ANC in patients with HIV infection. This allows greater use of myelosuppressive medications without the potentially life-threatening complications of neutropenia.