Oxidative stress, microparticles, and E-selectin do not depend on HIV suppression.

BACKGROUND: Oxidative stress and inflammation are considered predictors of diseases associated with aging. Markers of oxidative stress, inflammation, and endothelial activation were investigated in people with HIV on antiretroviral treatment to determine whether they had an immunosenescent phenotype that might predispose to the development of premature age-related diseases. PATIENTS AND METHODS: This study was conducted on 213 subjects with HIV. The control groups consisted of healthy HIV-negative adults. The level of oxidative stress was measured by assessing the production of malondialdehyde levels, which were detected by thiobarbituric acid reactive substance (TBARS) assay. The level of microparticles indicated the presence of inflammation and endothelial activation was measured by E-selectin levels. Significant differences were determined by appropriate statistical tests, depending on the distribution of variables. Relationships between continuous variables were quantified using Spearman's rank correlation coefficient. RESULTS: TBARS, and microparticle and E-selectin levels were significantly higher in untreated and treated subjects with HIV compared with HIV-negative controls (P<0.001). The levels of the investigated markers were not significantly different between untreated and treated patients and no significant correlation of these markers was found with CD4+ count, CD4+/CD8+ ratio, and the number of HIV-1 RNA copies. CONCLUSIONS: Elevated markers of oxidative stress, inflammatory and endothelial activation were independent of the virologic and immunologic status of people with HIV. These results support the hypothesis that residual viremia in cellular reservoirs of various tissues is a key factor related to the premature aging of the immune system and predisposition to the premature development of diseases associated with aging.

[Tenofovir alafenamide fumarate - a new generation of tenofovir].

Antiretroviral therapy as a life-long treatment has to meet the criteria of maximum efficiency while maintaining the highest possible level of safety and tolerance. Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug with an excellent effect of virological suppression. However, some patients can over time develop clinically significant nephrotoxicity or bone loss. Tenofovir alafenamide fumarate (TAF) is a novel prodrug of tenofovir (TFV) that is more stable in human plasma and more efficiently penetrates into target cells than TFV. Tenofovir converted from TAF reaches plasma concentration which is 90% lower than that of TFV converted from TDF. Conversely, the active metabolite converted from TAF reaches a higher intracellular level in target cells than TFV from TDF. This allows a substantial reduction of its oral dose, decreasing the risk for renal and bone toxicity. It is even possible to reduce the dose of TAF in case it is administered concurrently with cobicistat further improving its absorption and optimizing its pharmacokinetic profile. Pharmacokinetic properties are another factor substantially influencing its safety profile. TAF is not a substrate for renal organic anion transporters and thus shows no cytotoxicity related to their expression. Based on clinical trials, a fixed-dose combination tablet (single-tablet regimen) containing elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate was approved by the FDA in November 2015. This regimen showed higher efficacy, better safety profile and tolerance than TDF-based regiments. Recently, it has been approved in European Union countries.

[RILPIVIRINE -- a novel HIV-1 non-nucleoside reverse transcriptase inhibitor]. / RILPIVIRIN -- nový nenukleosidový inhibitor reverzní transkriptázy HIV-1.

The article summarizes the basic facts about the pharmacokinetic profile, metabolism and drug interactions of rilpivirine (RPV). This is the latest orally administered second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) for antiretroviral-naive patients with HIV-1 infection. Conformational flexibility and adaptability are the factors that dominantly determine the high resistance barrier of RPV and are the unique features of diarylpyrimidine inhibitors (DAPY inhibitors - 2nd generation NNRTIs). Multicentre studies ECHO and THRIVE are also reviewed. Current guidelines for the treatment of HIV/AIDS are mentioned as well as the role of RPV in current therapeutic regimens.

Acute toxoplasmosis-etiological factor for development of Hodgkin's lymphoma?

The case of an HIV-positive man treated for acute toxoplasmosis with no traces of malignancy is reported. A second lymph node extirpation was performed after 5 months, which identified the presence of Hodgkin and Reed-Sternberg (HRS) cells. This case suggests that toxoplasmosis may cause changes in the regulation of surrounding cells and induce neoplastic proliferation.

[Disseminated infection with Mycobacterium avium in a patient with newly diagnosed HIV infection]. / Diseminovana infekce Mycobacterium avium u pacienta s nove zjistenou HIV infekci.

In the Czech Republic, mycobacteriosis is relatively rare. The low incidence probably reflects high BCG coverage rates in the Czech population. Globally, the importance of BCG vaccine has been increasing, as a result of acquired immunodeficiencies, particularly HIV infection. The presented case report describes the course of disseminated mycobacteriosis in a Vietnamese asylum seeker with newly diagnosed advanced HIV infection. In HIV patients, disseminated mycobacteriosis, most frequently caused by members of Mycobacterium avium complex (MAC), is mostly manifested in the last stage, AIDS, with extremely severe immunodeficiency, or in immune reconstitution inflammatory syndrome (IRIS), shortly after initiation of antiretroviral therapy. From the beginning, the patient's condition was complicated by multiple simultaneous severe opportunistic infections which, together with gradually progressing atypical mycobacteriosis, resulted in overall exhaustion of the organism. The adverse prognosis of these infections is significantly influenced by prolonged diagnosis based on culture detection of slow-growing mycobacteria. In the above patient, the lethal course was contributed to by resistance to commonly used antitubercular drugs which was only detected post mortem due to time-consuming susceptibility tests.