FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2106855654> ?p ?o ?g. }

• W2106855654 abstract "After the use of combination antiretroviral (ARV) therapy led to improvements in survival among patients with HIV infection and AIDS [1], a wide variety of body composition and metabolic changes appeared that initially were blamed on HIV protease inhibitors (PIs) as a class [2]. However, the global changes attributed to PIs seemed unlikely, for several reasons [3]. First, an understanding of the literature published before the PI era indicates that some changes represented reversal of the effects of HIV infection—essentially, restoration to health. Second, studies always involved HIV-infected patients receiving therapy with 3 drugs, so attribution to a PI was not definitive. Third, the diverse structures of PIs, which were directed against a viral protease with little homology to mammalian proteases, made it unlikely that all PIs would have the same off-target complications at their respective therapeutic levels. Furthermore, facile theories often linked insulin resistance and hypertriglyceridemia.As HIV-infected patients have lived longer, there has been increasing concern over ARV drug toxicities, such as insulin resistance, hypertriglyceridemia with increases in atherogenic non–high-density lipoprotein cholesterol, and coronary artery disease. It therefore became important to define the direct complications of specific ARV drugs. As a consequence, many of us have tested the effects of ARV drugs, especially PIs, on healthy, HIV-seronegative volunteers, to separate the direct toxicities of the specific ARV drug from the effects of controlling HIV infection (reviewed in detail elsewhere [4]). Comparison of the effects seen in HIV-seronegative volunteers with the changes seen in HIV-infected patients receiving combination therapy or undergoing switch therapy in which 1 drug was changed has painted a clearer picture of ARV drug toxicity.We have learned that the increases in low-density lipoprotein cholesterol seen with combination therapy are mostly reversal of the decrease in low-density lipoprotein seen in the host response to HIV [4]. The similar decrease in high-density lipoprotein that is attributable to HIV infection is poorly responsive to PI-based therapy but improves significantly with nonnucleoside reverse-transcriptase inhibitor therapy, although not always back to normal. The increases seen in triglycerides are drug specific, because they are dominantly attributable to ritonavir-containing regimens and are not a general property of PI drugs. Indeed, there is evidence that efavirenz increases triglycerides. Indinavir is the most potent inducer of insulin resistance but has little effect on triglycerides. We have learned that time of exposure matters. Acute or short-term administration leads to more insulin resistance, whereas insulin resistance decreases with 4 weeks of exposure. Increases in triglycerides are seen within 2–4 weeks after initiation of ritonavir treatment. After longer periods, both PI and nonnucleoside reverse-transcriptase inhibitor regimens for HIV-infected individuals will lead to insulin resistance that likely represents restoration to health, including body composition changes [5]. The 4-week period is not enough to see any change in body composition; therefore, it makes a good time for study, because one can see the effects of most metabolic drugs and diets and there is enough time for the body to respond to acute metabolic changes [4].The article by Dube et al. [6] in this issue of Clinical Infectious Diseases extends these observations to another area, endothelial dysfunction, a vascular abnormality that predicts cardiovascular disease [7, 8]. Endothelial dysfunction has the advantage of being modulated within weeks, so it represents a more dynamic measure of cardiovascular risk that complements slowly changing direct measures of atherosclerosis, such as carotid intimamedial thickness. Endothelial dysfunction may also play a direct role in increasing atherosclerosis. Research groups from Indiana University had shown elsewhere that indinavir was a potent inducer of endothelial dysfunction in healthy, HIV-seronegative volunteers, but that effect was unrelated to the induction of insulin resistance [9–11]. Dube et al. [6] have published an informative study with negative results. Neither atazanavir nor lopinavir-ritonavir induced endothelial dysfunction in a similar 4-week exposure among HIV-seronegative volunteers, despite the fact that lopinavir-ritonavir induced its usual hypertriglyceridemia.Thus, Dube et al. [6] have given us several important findings. First, as with other complications of ARV therapy, induction of endothelial dysfunction is drug specific, not class specific. Second, induction of endothelial dysfunction may be a direct effect, because it has now been shown that it is not merely mediated by hypertriglyceridemia or insulin resistance, although these metabolic changes may be associated with endothelial dysfunction under other circumstances [12]. Finally, Dube et al. [6] point out that, in looking for an explanation of how PIs as a class might induce myocardial infarction above that expected from the changes in lipids [13], induction of endothelial dysfunction is no longer a likely candidate. Further research in this area is needed, but the recent finding that PI therapy as a class is associated with higher fibrinogen levels [14] suggests one possible mechanism. In the interim, studies such as those by Dube et al. [6] and others [4] allow us to more intelligently advise our patients about the possible complications of very effective drugs." @default.
• W2106855654 created "2016-06-24" @default.
• W2106855654 creator A5048434963 @default.
• W2106855654 date "2008-08-15" @default.
• W2106855654 modified "2023-09-26" @default.
• W2106855654 title "Editorial Commentary:Understanding the Complications of Antiretroviral Drugs" @default.
• W2106855654 cites W1767400858 @default.
• W2106855654 cites W1977705956 @default.
• W2106855654 cites W2006417252 @default.
• W2106855654 cites W2010095497 @default.
• W2106855654 cites W2033049238 @default.
• W2106855654 cites W2034059696 @default.
• W2106855654 cites W2052628368 @default.
• W2106855654 cites W2072399876 @default.
• W2106855654 cites W2100892346 @default.
• W2106855654 cites W2105343975 @default.
• W2106855654 cites W2141665762 @default.
• W2106855654 cites W2142037089 @default.
• W2106855654 cites W2318289184 @default.
• W2106855654 cites W2324473093 @default.
• W2106855654 doi "https://doi.org/10.1086/590155" @default.
• W2106855654 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3170412" @default.
• W2106855654 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18611156" @default.
• W2106855654 hasPublicationYear "2008" @default.
• W2106855654 type Work @default.
• W2106855654 sameAs 2106855654 @default.
• W2106855654 citedByCount "6" @default.
• W2106855654 countsByYear W21068556542012 @default.
• W2106855654 countsByYear W21068556542015 @default.
• W2106855654 crossrefType "journal-article" @default.
• W2106855654 hasAuthorship W2106855654A5048434963 @default.
• W2106855654 hasBestOaLocation W21068556541 @default.
• W2106855654 hasConcept C114851261 @default.
• W2106855654 hasConcept C126322002 @default.
• W2106855654 hasConcept C203014093 @default.
• W2106855654 hasConcept C2776919658 @default.
• W2106855654 hasConcept C2777391703 @default.
• W2106855654 hasConcept C2778163477 @default.
• W2106855654 hasConcept C2778913445 @default.
• W2106855654 hasConcept C2779306644 @default.
• W2106855654 hasConcept C2780035454 @default.
• W2106855654 hasConcept C71924100 @default.
• W2106855654 hasConcept C86803240 @default.
• W2106855654 hasConcept C89423630 @default.
• W2106855654 hasConcept C98274493 @default.
• W2106855654 hasConceptScore W2106855654C114851261 @default.
• W2106855654 hasConceptScore W2106855654C126322002 @default.
• W2106855654 hasConceptScore W2106855654C203014093 @default.
• W2106855654 hasConceptScore W2106855654C2776919658 @default.
• W2106855654 hasConceptScore W2106855654C2777391703 @default.
• W2106855654 hasConceptScore W2106855654C2778163477 @default.
• W2106855654 hasConceptScore W2106855654C2778913445 @default.
• W2106855654 hasConceptScore W2106855654C2779306644 @default.
• W2106855654 hasConceptScore W2106855654C2780035454 @default.
• W2106855654 hasConceptScore W2106855654C71924100 @default.
• W2106855654 hasConceptScore W2106855654C86803240 @default.
• W2106855654 hasConceptScore W2106855654C89423630 @default.
• W2106855654 hasConceptScore W2106855654C98274493 @default.
• W2106855654 hasLocation W21068556541 @default.
• W2106855654 hasLocation W21068556542 @default.
• W2106855654 hasLocation W21068556543 @default.
• W2106855654 hasLocation W21068556544 @default.
• W2106855654 hasOpenAccess W2106855654 @default.
• W2106855654 hasPrimaryLocation W21068556541 @default.
• W2106855654 hasRelatedWork W125489432 @default.
• W2106855654 hasRelatedWork W1563109184 @default.
• W2106855654 hasRelatedWork W183057856 @default.
• W2106855654 hasRelatedWork W1992638484 @default.
• W2106855654 hasRelatedWork W2020886039 @default.
• W2106855654 hasRelatedWork W2031854410 @default.
• W2106855654 hasRelatedWork W2032119499 @default.
• W2106855654 hasRelatedWork W2035044461 @default.
• W2106855654 hasRelatedWork W2039794360 @default.
• W2106855654 hasRelatedWork W2057136465 @default.
• W2106855654 hasRelatedWork W2081421896 @default.
• W2106855654 hasRelatedWork W2108978263 @default.
• W2106855654 hasRelatedWork W2115059395 @default.
• W2106855654 hasRelatedWork W2132208512 @default.
• W2106855654 hasRelatedWork W2262286524 @default.
• W2106855654 hasRelatedWork W2266090773 @default.
• W2106855654 hasRelatedWork W2414906795 @default.
• W2106855654 hasRelatedWork W2470624453 @default.
• W2106855654 hasRelatedWork W2188184548 @default.
• W2106855654 hasRelatedWork W2396724657 @default.
• W2106855654 isParatext "false" @default.
• W2106855654 isRetracted "false" @default.
• W2106855654 magId "2106855654" @default.
• W2106855654 workType "editorial" @default.