scholarly journals Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
Helen Kovari ◽  
Caroline A. Sabin ◽  
Bruno Ledergerber ◽  
Lene Ryom ◽  
Peter Reiss ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Liver Enzyme ◽  
Chronic Liver ◽  
Liver Enzyme Elevation ◽  
Immunodeficiency Virus ◽  
Short And Long Term ◽  
Enzyme Elevation ◽  
Hiv Drugs ◽  
Anti Hiv

Abstract Background.  Although human immunodeficiency virus (HIV)-positive persons on antiretroviral therapy (ART) frequently have chronic liver enzyme elevation (cLEE), the underlying cause is often unclear. Methods.  Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study participants without chronic viral hepatitis were observed to the earliest of cLEE (elevated aminotransferase ≥6 months), death, last follow-up, or January 2, 2014. Antiretroviral treatment exposure was categorized as follows: no exposure and ongoing short- and long-term exposure (<2 or ≥2 years) after initiation. Association between development of cLEE and ART exposure was investigated using Poisson regression. Results.  Among 21 485 participants observed for 105 413 person-years (PY), 6368 developed cLEE (incidence 6.04/100 PY; 95% confidence interval [CI], 5.89–6.19). Chronic liver enzyme elevation was associated with short-and long-term exposure to didanosine (<2 years rate ratio [RR] = 1.29, 95% CI, 1.11–1.49; >2 years RR = 1.26, 95% CI, 1.13–1.41); stavudine (<2 years RR = 1.51, 95% CI, 1.26–1.81; >2 years RR = 1.17, 95% CI, 1.03–1.32), and tenofovir disoproxil fumarate (<2 years RR = 1.55, 95% CI, 1.40–1.72; >2 years RR = 1.18, 95% CI, 1.05–1.32), but only short-term exposure to nevirapine (<2 years RR = 1.44, 95% CI, 1.29–1.61), efavirenz (<2 years RR = 1.14, 95% CI, 1.03–1.26), emtricitabine (<2 years RR = 1.18, 95% CI, 1.04–1.33), and atazanavir (<2 years RR = 1.20, 95% CI, 1.04–1.38). Chronic liver enzyme elevation was not associated with use of lamivudine, abacavir, and other protease inhibitors. Mortality did not differ between participants with and without cLEE. Conclusions.  Although didanosine, stavudine, nevirapine, and efavirenz have been described to be hepatotoxic, we additionally observed a consistent association between tenofovir and cLEE emerging within the first 2 years after drug initiation. This novel tenofovir-cLEE signal should be further investigated.

scholarly journals Novel 4′-Substituted Stavudine Analog with Improved Anti-Human Immunodeficiency Virus Activity and Decreased Cytotoxicity

2004 ◽  
Vol 48 (5) ◽  
pp. 1640-1646 ◽  
Author(s):  
Ginger E. Dutschman ◽  
Susan P. Grill ◽  
Elizabeth A. Gullen ◽  
Kazuhiro Haraguchi ◽  
Shingo Takeda ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Drug ◽  
Antiviral Effect ◽  
Immunodeficiency Virus ◽  
Delayed Toxicity ◽  
Hiv Drugs ◽  
Further Development ◽  
Anti Hiv ◽  
Better Than

ABSTRACT The antiviral drug 2′,3′-didehydro-3′-deoxythymidine (D4T; also know as stavudine and Zerit), which is used against human immunodeficiency virus (HIV), causes delayed toxicity (peripheral neuropathy) in long-term use. After examining a series of 2′,3′-didehydro-3′-deoxy-4′-substituted thymidine (4′-substituted D4T) analogs, 4′-ethynyl D4T was found to have a fivefold-better antiviral effect and to cause less cellular and mitochondrial toxicity than D4T. The antiviral activity of this compound can be reversed by dThd but not by dCyd. The compound acted synergistically with β-l-2′,3′-deoxy-3′-thiacytidine (also known as lamivudine) and β-l-2′,3′-dideoxy-2′,3′-didehydro-5-fluorocytidine (also known as elvucitabine) and additively with 2′,3′-dideoxyinosine (also known as didanosine and Videx) and 3′-azido-3′-deoxythymidine (also known as Retovir and zidovudine) against HIV. 4′-Ethynyl D4T is phosphorylated by purified human thymidine kinase 1 (TK-1) from CEM cells with a faster relative V max and a lower Km value than D4T. The efficiency of TK-1 in the phosphorylation of 4′-ethynyl D4T is fourfold better than that of D4T. While D4T is broken down by the catabolic enzyme thymidine phosphorylase, the level of breakdown of 4′-ethynyl D4T was below detection. Since 4′-ethynyl D4T has increased anti-HIV activity and decreased toxicity and interacts favorably with other currently used anti-HIV drugs, it should be considered for further development as an anti-HIV drug.

scholarly journals Potent Synergistic Anti-Human Immunodeficiency Virus (HIV) Effects Using Combinations of the CCR5 Inhibitor Aplaviroc with Other Anti-HIV Drugs

2008 ◽  
Vol 52 (6) ◽  
pp. 2111-2119 ◽  
Author(s):  
Hirotomo Nakata ◽  
Seth M. Steinberg ◽  
Yasuhiro Koh ◽  
Kenji Maeda ◽  
Yoshikazu Takaoka ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Synergistic Effects ◽  
Immunodeficiency Virus ◽  
Approved Drugs ◽  
Hiv Drugs ◽  
Nonparametric Statistical ◽  
Anti Hiv ◽  
Ccr5 Inhibitor ◽  
Hiv 1

ABSTRACT Aplaviroc (AVC), an experimental CCR5 inhibitor, potently blocks in vitro the infection of R5-tropic human immunodeficiency virus type 1 (R5-HIV-1) at subnanomolar 50% inhibitory concentrations. Although maraviroc is presently clinically available, further studies are required to determine the role of CCR5 inhibitors in combinations with other drugs. Here we determined anti-HIV-1 activity using combinations of AVC with various anti-HIV-1 agents, including four U.S. Food and Drug Administration-approved drugs, two CCR5 inhibitors (TAK779 and SCH-C) and two CXCR4 inhibitors (AMD3100 and TE14011). Combination effects were defined as synergistic or antagonistic when the activity of drug A combined with B was statistically greater or less, respectively, than the additive effects of drugs A and A combined and drugs B and B combined by using the Combo method, described in this paper, which provides (i) a flexible choice of interaction models and (ii) the use of nonparametric statistical methods. Synergistic effects against R5-HIV-1Ba-L and a 50:50 mixture of R5-HIV-1Ba-L and X4-HIV-1ERS104pre (HIV-1Ba-L/104pre) were seen when AVC was combined with zidovudine, nevirapine, indinavir, or enfuvirtide. Mild synergism and additivity were observed when AVC was combined with TAK779 and SCH-C, respectively. We also observed more potent synergism against HIV-1Ba-L/104pre when AVC was combined with AMD3100 or TE14011. The data demonstrate a tendency toward greater synergism with AVC plus either of the two CXCR4 inhibitors compared to the synergism obtained with combinations of AVC and other drugs, suggesting that the development of effective CXCR4 inhibitors may be important for increasing the efficacies of CCR5 inhibitors.

scholarly journals Mechanism of Anti-Human Immunodeficiency Virus Activity of β-d-6-Cyclopropylamino-2′,3′-Didehydro-2′,3′-Dideoxyguanosine

2005 ◽  
Vol 49 (5) ◽  
pp. 1994-2001 ◽  
Author(s):  
Adrian S. Ray ◽  
Brenda I. Hernandez-Santiago ◽  
Judy S. Mathew ◽  
Eisuke Murakami ◽  
Carey Bozeman ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Oral Delivery ◽  
Mononuclear Cells ◽  
Cellular Metabolism ◽  
Nucleoside Analogs ◽  
Immunodeficiency Virus ◽  
Moderate Resistance ◽  
Hiv Drugs ◽  
Anti Hiv

ABSTRACT To better understand the importance of the oxygen in the ribose ring of planar unsaturated nucleoside analogs that target human immunodeficiency virus (HIV), a 6-cyclopropyl-substituted prodrug of 2′,3′-didehydro-2′,3′-dideoxyguanosine (cyclo-d4G) was synthesized, and its cellular metabolism, antiviral activity, and pharmacokinetic behavior were studied. Cyclo-d4G had selective anti-HIV activity in primary blood mononuclear cells (PBMCs), effectively inhibiting the LAI strain of HIV-1 by 50% at 1.1 ± 0.1 μM while showing 50% inhibition of cell viability at 84.5 μM. The antiviral activity in PBMCs was not markedly affected by mutations of methionine to valine at position 184 or by thymidine-associated mutations in the viral reverse transcriptase. Mutations of leucine 74 to valine and of lysine 65 to arginine had mild to moderate resistance (as high as fivefold). Studies to delineate the mechanism of cellular metabolism and activation of cyclo-d4G showed reduced potency in inhibiting viral replication in the presence of the adenosine/adenylate deaminase inhibitor 2′-deoxycoformycin, implying that the antiviral activity is due to its metabolism to the 2′-dGTP analog d4GTP. Intracellular formation of sugar catabolites illustrates the chemical and potentially enzymatic instability of the glycosidic linkage in d4G. Further studies suggest that cyclo-d4G has a novel intracellular phosphorylation pathway. Cyclo-d4G had a lower potential to cause mitochondrial toxicity than 2′,3′-dideoxycytidine and 2′,3′-didehydro-3′-deoxythymidine in neuronal cells. Also, cyclo-d4G had advantageous synergism with many currently used anti-HIV drugs. Poor oral bioavailability observed in rhesus monkeys may be due to the labile glycosidic bond, and special formulation may be necessary for oral delivery.

Excessive Weight Gain Associated With Dolutegravir Initiation in a 10-Year-Old Female With Perinatally Acquired Human Immunodeficiency Virus: A Case Report and Review of the Literature

2020 ◽  
Author(s):  
J Li ◽  
E H Yusuf ◽  
A L Agwu
Keyword(s):  
Human Immunodeficiency Virus ◽  
Weight Gain ◽  
Antiretroviral Treatment ◽  
Review Of The Literature ◽  
Excessive Weight Gain ◽  
Excessive Weight ◽  
Immunodeficiency Virus ◽  
Perinatally Acquired ◽  
Short And Long Term

Abstract Children with perinatally acquired human immunodeficiency virus (PHIV) face a lifetime of combination antiretroviral treatment that often includes dolutegravir (DTG). DTG, an integrase strand inhibitor that has been linked to weight gain in adults, is increasingly being used in children. Understanding its potential short- and long-term sequelae in children is critically important. We report a case of excessive weight gain in a child with PHIV on DTG and provide a brief literature review.

scholarly journals Sophorolipids, Microbial Glycolipids with Anti-Human Immunodeficiency Virus and Sperm-Immobilizing Activities

2005 ◽  
Vol 49 (10) ◽  
pp. 4093-4100 ◽  
Author(s):  
Vishal Shah ◽  
Gustavo F. Doncel ◽  
Theodoros Seyoum ◽  
Kristin M. Eaton ◽  
Irina Zalenskaya ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cytotoxic Activities ◽  
Cell Toxicity ◽  
Human Semen ◽  
Virucidal Activity ◽  
Structure Activity ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Topical Microbicide

ABSTRACT The increased incidence of human immunodeficiency virus (HIV)/AIDS disease in women aged 15 to 49 years has identified the urgent need for a female-controlled, efficacious, and safe vaginal topical microbicide. To meet this challenge, sophorolipid (SL) produced by Candida bombicola and its structural analogs have been studied in this report for their spermicidal, anti-HIV, and cytotoxic activities. The sophorolipid diacetate ethyl ester derivative is the most potent spermicidal and virucidal agent of the series of SLs studied. Its virucidal activity against HIV and sperm-immobilizing activity against human semen are similar to those of nonoxynol-9. However, it also induced enough vaginal cell toxicity to raise concerns about its applicability for long-term microbicidal contraception. Its structure-activity relationship has been established for creating new analogs with less cytotoxicity and higher activity.

scholarly journals The Incidence and Risk Factors Associated with Chronic Liver Enzyme Elevation (cLEE) in HIV-Monoinfected Persons

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S220-S221
Author(s):  
Shannon Wood ◽  
Morgan Byrne ◽  
Robert Deiss ◽  
Jason Okulicz ◽  
Thomas O’Bryan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Enzyme ◽  
Chronic Liver ◽  
Liver Enzyme Elevation ◽  
Factors Associated ◽  
Enzyme Elevation
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