scholarly journals Resistance to HIV Integrase Strand Transfer Inhibitors Among Clinical Specimens in the United States, 2009–2012

2013 ◽  
Vol 58 (3) ◽  
pp. 423-431 ◽  
Author(s):  
Christopher B. Hurt ◽  
Joseph Sebastian ◽  
Charles B. Hicks ◽  
Joseph J. Eron
Keyword(s):  
United States ◽  
The United States ◽  
Strand Transfer ◽  
Hiv Integrase ◽  
Clinical Specimens ◽  
Integrase Strand Transfer Inhibitors

scholarly journals Integrase Strand Transfer Inhibitors and Weight Gain in Children and Youth with Perinatal HIV in the DC Cohort

2021 ◽  
Author(s):  
Wei Li A Koay ◽  
Sahera Dirajlal-Fargo ◽  
Matthew E Levy ◽  
Paige Kulie ◽  
Anne Monroe ◽  
...  
Keyword(s):  
United States ◽  
Weight Gain ◽  
The United States ◽  
Rate Of Change ◽  
Children And Youth ◽  
Strand Transfer ◽  
Z Score ◽  
Perinatal Hiv ◽  
Integrase Strand Transfer Inhibitors

Abstract We conducted a retrospective analysis of 38 children and youth with HIV (aged 0-<20 years) in the United States and report an increased rate of change of BMI-for-age z-score after initiating integrase strand transfer inhibitors (+0.19 z-score units/year, 95% CI 0.01, 0.37, p=0.036) for a median follow-up of 527.5 days.

scholarly journals The Terminal (Catalytic) Adenosine of the HIV LTR Controls the Kinetics of Binding and Dissociation of HIV Integrase Strand Transfer Inhibitors

Biochemistry ◽  
2008 ◽  
Vol 47 (51) ◽  
pp. 13481-13488 ◽  
Author(s):  
David R. Langley ◽  
Himadri K. Samanta ◽  
Zeyu Lin ◽  
Michael A. Walker ◽  
Mark R. Krystal ◽  
...  
Keyword(s):  
Strand Transfer ◽  
Hiv Integrase ◽  
Integrase Strand Transfer Inhibitors ◽  
Kinetics Of

scholarly journals Comparison of the Babesia duncani (WA1) IgG Detection Rates among Clinical Sera Submitted to a Reference Laboratory for WA1 IgG Testing and Blood Donor Specimens from Diverse Geographic Areas of the United States

2010 ◽  
Vol 17 (11) ◽  
pp. 1729-1733 ◽  
Author(s):  
Harry E. Prince ◽  
Mary Lapé-Nixon ◽  
Hemlata Patel ◽  
Cindy Yeh
Keyword(s):  
United States ◽  
Blood Donor ◽  
Detection Rate ◽  
Pacific Coast ◽  
The United States ◽  
Babesia Microti ◽  
Clinical Specimens ◽  
Ebv Infection ◽  
Related Organism ◽  
The Pacific

ABSTRACT All reported cases of WA1 babesiosis have occurred in the Pacific coast region of the United States, suggesting that WA1 is limited to this geographic area. However, we detected WA1 IgG in 27% of clinical sera sent to our laboratory for WA1 IgG testing from across the United States over a 2-year period, suggesting that exposure to WA1 or a closely related organism occurs outside Pacific coast states. We sought to determine if this high WA1 IgG detection rate among clinical specimens merely reflects WA1 seroprevalence outside the Pacific region. WA1 IgG, as well as Babesia microti IgG, was measured in 900 blood donor specimens from 9 states. Overall seroprevalence was 2.0% for WA1 and 0.4% for B. microti; regional seroprevalences ranged from 0 to 4% and 0 to 2%, respectively. Additional studies were performed to determine if WA1 IgG reactivity was attributable to polyclonal B-cell activation associated with acute Epstein-Barr virus (EBV) infection; 40 WA1 IgG-positive clinical sera and the 18 WA1 IgG-positive blood donor specimens were all negative for EBV capsid antigen (EBVCA) IgM (a marker of acute EBV infection), and 40 EBVCA IgM-positive sera were all negative for WA1 IgG. These findings indicate that the high WA1 IgG detection rate among clinical specimens does not simply reflect the national WA1 seroprevalence among blood donors or nonspecific reactivity due to acute EBV infection. Rather, the findings suggest that infection with WA1 or a related organism is more common than indicated by the literature and is not limited to Pacific coast states.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide discontinuation and return to normal weight

2020 ◽  
pp. 095646242096434 ◽  
Author(s):  
Blake Max ◽  
Patricia DeMarais
Keyword(s):  
Weight Gain ◽  
Normal Weight ◽  
Strand Transfer ◽  
Hiv Integrase ◽  
Combination Antiretroviral Therapy ◽  
Excessive Weight ◽  
Integrase Strand Transfer Inhibitors ◽  
Baseline Weight ◽  
Tenofovir Alafenamide

HIV integrase strand transfer inhibitors (INSTI) are considered well tolerated with few treatment-limiting adverse effects. However, emerging data from clinical trials has identified excessive weight gain possibly due to INSTI alone or with tenofovir alafenamide as a new and possible long-term complication of combination antiretroviral therapy (cART). Identifying who is at greatest risk and whether the unintended weight gain is reversible remain unanswered questions. We report a return to baseline weight after switching back to tenofovir disoproxil/emtricitabine/efavirenz (Atripla®) in a woman who had profound weight gain due to tenofovir alafenamide/emtricitabine/cobicistat/elvitegravir (Genvoya®).

Design, Synthesis and In Vitro Evaluation of 4-Oxo-6-Substituted Phenyl- 2-Thioxo1,2,3,4-Tetrahydropyrimidine-5-Carbonitrile Derivatives as HIV Integrase Strand Transfer Inhibitors

2020 ◽  
Vol 17 ◽  
Author(s):  
Pankaj Wadhwa ◽  
Priti Jain ◽  
Hemant R. Jadhav
Keyword(s):  
In Silico ◽  
Strand Transfer ◽  
Hiv Integrase ◽  
Chromosomal Dna ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
In Vitro Evaluation ◽  
Integrase Strand Transfer Inhibitors ◽  
Hiv 1

Aim:: To design, synthesis and in vitro evaluation of 4-oxo-6-substituted phenyl-2-thioxo1,2,3,4- tetrahydropyrimidine-5-carbonitrile derivatives as HIV integrase strand transfer inhibitors. Background:: Human immunodeficiency virus-1 (HIV-1), a member of retroviridae family, is the primary causative agent of acquired immunodeficiency syndrome (AIDS). Three enzymes viz: integrase (IN), reverse transcriptase (RT) and protease play important role in its replication cycle. HIV-1 integrase is responsible for the incorporation of viral DNA into human chromosomal DNA by catalyzing two independent reactions, 3′-processing (3′-P) and strand transfer (ST), which are observed as the “point of no-return” in HIV infection. Objective:: To develop inhibitors against HIV integrase strand transfer step. Methods:: Our previous results indicated that tetrahydro pyrimidine-5-carboxamide derivatives are potent HIV-1 IN inhibitors (unpublished results from our laboratory). Taking clue from above studies and our own experience, we hypothesized 4- oxo-6-substituted phenyl-2-thioxo1,2,3,4-tetrahydropyrimidine-5-carbonitrile analogues (14a to 14n) as inhibitors of HIV-1 Integrase strand transfer. As shown in figure 2, prototype compound 14 can be viewed as hybrid structure having characteristics of dihydropyrimidine derivatives 10-12 and tyrphostin 13. Result:: A total of fourteen derivatives of 4-oxo-6-substituted phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (14a-14n) were synthesized and evaluated using HIV-1 Integrase Assay Kit (Xpressbio Life Science Products, USA). The percentage inhibition of all compounds was investigated at 10 μM concentration and IC50 value of few highly active compounds was studied. The obtained results were validated by in silico molecular docking study using Glide (maestro version 9.3, Schrödinger suite) in extra precision (XP) mode. Conclusion:: Fourteen 4-oxo-6-substituted phenyl-2-thioxo 1,2,3,4-tetrahydropyrimidine-5-carbonitrile analogues were synthesized and evaluated for HIV-1 IN inhibitory activity. Three compounds 14a, 14e, and 14h exhibited significant percentage inhibition of HIV-1 IN. There was good in vitro - in silico correlation. However, none of the derivative was active against HIV-1 and HIV-2 below their cytotoxic concentration. It needs to be seen whether these compounds can be explored further for their anti-HIV or cytotoxic potential.

scholarly journals Systematic determination of in vitro phenotypic resistance to HIV-1 integrase strand transfer inhibitors from clinical samples

2019 ◽  
Author(s):  
Aniqa Shahid ◽  
Wendy W. Zhang ◽  
Vincent Montoya ◽  
Peter K. Cheung ◽  
Natalia Oliveira ◽  
...  
Keyword(s):  
Site Directed Mutagenesis ◽  
Cross Resistance ◽  
Clinical Samples ◽  
Strand Transfer ◽  
Hiv Integrase ◽  
Phenotypic Resistance ◽  
Integrase Strand Transfer Inhibitors ◽  
Hiv 1

ABSTRACTPhenotypic resistance data is relatively sparse for the newest HIV-1 integrase strand transfer inhibitors (INSTIs), dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB). In this study, we report the phenotypic susceptibility of a large panel of oligo-clonal patient-derived HIV-1 integrase viruses. Representative clinical samples (N=141) were selected from a large database (N=17,197) of clinically-derived HIV integrase sequences, based on the presence of permutations of substitutions at 27 pre-defined positions in integrase (N=288). HIV-1 RNA was extracted from patient samples and diluted to approximately 500 HIV RNA copies/mL. Using an “oligo-clonal” amplification approach to achieve single-copy amplification, these dilutions were subjected to 12 parallel RT-PCR reactions to amplify integrase. Confirmed clonal amplicons were co-transfected with linearized pNL4.3∆int into CEM-GXR cells. In total, 162 HIV-1 viruses that carried no mixtures and had a unique sequence were harvested, and phenotyped in MT4-LTR-EGFP cells subsequently. Variants with the highest fold change (FC) had G140S and Q148R/H and resistant to all five drugs; R263K was the only single variant conferring >3-FC to DTG, BIC and CAB. There was extensive cross-resistance between DTG, BIC, and CAB and phenotypic resistance values for all the three INSTIs were almost collinear. The greatest exceptions were variants with N155H/G163E or L74I/T97M/F121C/V151I/E157Q/G163K, where both had >70-FC for CAB, while <3-FC for DTG and BIC. While site-directed mutagenesis is invaluable; the systematic selection of representative mutational patterns observedin vivoprovides an efficient way to identify clinically relevant drug resistance.

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