Human immunodeficiency virus (HIV) type 1 (HIV-1) integrase is an underutilized drug target for the treatment of HIV infection. One limiting factor is the lack of costructural data for use in the rational design or modification of integrase inhibitors. Tn5 transposase is a structurally well characterized, related protein that may serve as a useful surrogate. However, little data exist on inhibi...

Expert guidelines for antiretroviral therapy (ART) now recommend ART as soon as possible in all HIV infected persons to reduce the risk of disease progression and prevent transmission. The goal of this observational study was to evaluate the impact of very early ART initiation and regimen type on time to viral suppression. We evaluated time to viral suppression among 86 persons with newly-diagn...

HIV drug resistance has been one of the major obstacles to HIV eradication and has contributed to the need for the constant development of new antiretroviral drugs over the past 25 years. With the recent approval of dolutegravir for human therapy by the U.S. Food and Drug Administration, health practitioners may soon have access to three integrase strand transfer inhibitors to treat individuals...

Enantioselective total synthesis of the recently isolated, novel polyketide natural product (+)-integrasone has been accomplished from the readily available Diels-Alder adduct of cyclopentadiene and p-benzoquinone. An enzymatically desymmetrized epoxyquinone building block has been elaborated through a series of regio- , chemo- and stereocontrolled steps to the final bicyclic framework of the n...

A sequencing assay for detection of mutations conferring resistance to human immunodeficiency virus type 1 (HIV-1) integrase inhibitors raltegravir and elvitegravir was developed using the automated TruGene sequencing system. The assay returned clear sequencing results for samples with >or=500 RNA copies/ml for mutation detection and HIV-1 subtyping across a spectrum of HIV-1 subtypes.

The introduction of integrase inhibitors as a new drug class for treatment of HIV have added a very potent and extremely well tolerated new treatment option to the HIV-armentarium. Particularly in patients with previously developed drug resistance, the availability of new active drugs offers great hope. Moreover, the in general excellent safety profile offers numerous opportunities for all line...

8-Hydroxy-2-[2-(3-hydroxy-4-methoxyphenyl)ethenyl]-7-quinoline carboxylic acid and 8-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethenyl]-7-quinoline carboxylic acid inhibit the processing and strand transfer reactions catalyzed by HIV-1 integrase with an IC50 of 2 microM. Some of their spectral properties are briefly reported. Their fluorescence is so weak that it is of no use in an experimental d...

Recently, we have described the design and characterization of oligonucleotides containing only G and T bases, i.e. T30695 and T30177, that are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in culture (Jing, N., Rando, R. F., Pommier, Y., and Hogan, M. E. (1997) Biochemistry 36, 12498-12505). To understand that observation and to rationalize the generally high the...

Background HIV-1 integrase is responsible for the transfer of virally encoded DNA into the host chromosome. The process of integration occurs through 3 essential steps: formation of the preintegration viral DNA complex, 3’processing and 5’ strand transfers. Provirus ancestral pol protein is a component of preintegration viral DNA complex, which has reverse transcriptase domain, Ribonuclease H l...

T30177 is a G-rich oligonucleotide with the sequence (GTGGTGGGTGGGTGGGT) which inhibits the HIV-1 integrase activity at nanomolar concentrations. Here we show that this DNA sequence forms in K(+) solution a dimeric G-quadruplex structure comprising a total of six G-tetrad layers through the stacking of two propeller-type parallel-stranded G-quadruplex subunits at their 5'-end. All twelve guanin...