ABSTRACT Although combination antiretroviral therapy has resulted in a considerable improvement the treatment of human immunodeficiency virus (HIV) type 1 (HIV-1) infection, emergence resistant is significant obstacle to effective management HIV infection and AIDS. We have developed novel phenotypic drug susceptibility assay that may be useful guiding improving long-term suppression replication. Susceptibility protease (PR) reverse transcriptase (RT) inhibitors measured by using resistance...

Most human immunodeficiency virus type 1 (HIV-1) strains require either the CXCR4 or CCR5 chemokine receptor to efficiently enter cells. Blocking viral binding these coreceptors is an attractive therapeutic target. Currently, several coreceptor antagonists are being evaluated in clinical trials that characterization of tropism for enrollment. In this report, we describe development automated and accurate procedure determining HIV-1 (Trofile) its validation routine laboratory testing....

Inhibiting human immunodeficiency virus type 1 (HIV-1) infection by blocking the host cell coreceptors CCR5 and CXCR4 is an emerging strategy for antiretroviral therapy. Currently, several novel coreceptor inhibitors are being developed in clinic, early results have proven promising. In this report, we describe a antagonist, vicriviroc (formerly SCH-D or SCH 417690), with improved antiviral activity pharmacokinetic properties compared to those of SCH-C, previously described antagonist. Like...

The human immunodeficiency virus type 1 (HIV-1) integrase mutations N155H and Q148R(H)(K) that reduce susceptibility to the inhibitor raltegravir have been identified in patients failing treatment regimens containing raltegravir. Whether these resistance occur individually or combination within a single genome has not defined, nor do we fully understand impact of primary other secondary on viral replication capacity. To address important questions, investigated capacity viruses at positions...

In human immunodeficiency virus type 1 (HIV-1) subtype B, CXCR4 coreceptor use ranges from approximately 20% in early infection to 50% advanced disease. Coreceptor by non-subtype B HIV is less well characterized. We studied tropism of A and D HIV-1 collected 68 pregnant, antiretroviral drug-naive Ugandan women (HIVNET 012 trial). None 33 or 10 A/D-recombinant viruses used the coreceptor. contrast, nine (36%) 25 both CCR5 coreceptors. Clonal analyses samples with dual mixed revealed...

Abstract Background Clinical studies have shown that integrase strand transfer inhibitors can be used to treat HIV-1 infection. Although the first-generation are susceptible emergence of resistance mutations impair their efficacy in therapy, such has not been identified date drug-naïve patients who treated with second-generation inhibitor dolutegravir. During previous vitro selection study, we a R263K mutation as most common substitution arise presence dolutegravir H51Y arising secondary...

Although CXCR4-tropic viruses are relatively uncommon among untreated human immunodeficiency virus (HIV)-infected individuals except during advanced immunodeficiency, the prevalence of treated patients with detectable viremia is unknown. To address this issue, viral coreceptor usage was measured a single-cycle recombinant-virus phenotypic entry assay in treatment-naive and HIV-infected participants sampled from 2 clinic-based cohorts. Of 182 participants, 75 (41%) harbored dual/mixed or...

Newly infected subjects acquire a limited number of human immunodeficiency virus type 1 (HIV-1) variants with specific genotypic and phenotypic features from the array viruses present in chronically transmitting partner.We examined HIV-1 envelope sequences earliest available serum sample after acquisition 13 newly their epidemiologically linked HIV-1-infected heterosexual partner. Samples both members were collected on same day Rakai Community Cohort Study.Ten couples subtype D HIV-1, 3...

Viral entry inhibitors represent an emerging mode of therapy for human immunodeficiency virus type 1 (HIV-1) infection. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. binds to the viral surface glycoprotein gp120 and blocks attachment into CD4(+) cells. Previously, demonstrated antiviral activity without significant toxicity when tested at single doses ranging 10 mg/kg. In this study, 12 HIV-infected...

Dolutegravir (DTG) is the latest antiretroviral (ARV) approved for treatment of human immunodeficiency virus (HIV) infection. The G118R substitution, previously identified with MK-2048 and raltegravir, may represent initial substitution in a dolutegravir resistance pathway. We have found that subtype C integrase proteins low enzymatic cost associated mostly at strand transfer step integration, compared to either B or recombinant CRF02_AG proteins. Subtype circulating form AG (CRF02_AG)...

Suboptimal treatment of human immunodeficiency virus type 1 (HIV-1) infection with nonnucleoside reverse transcriptase inhibitors (NNRTI) often results in the rapid selection drug-resistant virus. Several amino acid substitutions at position 190 (RT) have been associated reduced susceptibility to NNRTI, especially nevirapine (NVP) and efavirenz (EFV). In present study, effects various observed viruses obtained from NNRTI-experienced patients were characterized patient-derived HIV isolates...

Human immunodeficiency virus type 1 (HIV-1) coreceptor tropism, the ability of to enter cells via CCR5 or CXCR4, is a viral characteristic mediated by envelope gene. The impact tropism on natural history HIV-1 infection has not been fully explored.Coreceptor was measured using recombinant single-cycle assay plasma specimens obtained at baseline from 126 children and adolescents in Hemophilia Growth Development Study cohort who were enrolled 1989 through 1990 underwent follow-up...

Many studies have demonstrated that the third variable region (V3) of human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) is a major determinant coreceptor tropism. Other regions in surface gp120 subunit Env can modulate tropism manner not fully understood. In this study, we evaluated effect env determinants outside V3 on usage through analysis (i) patient-derived clones differ tropism, (ii) chimeric sequences, and (iii) site-directed mutants. The introduction distinct...

Although integrase inhibitors are highly effective in the management of drug-resistant HIV, some patients fail to achieve durable viral suppression. The long-term consequences inhibitor failure have not been well defined.We identified 29 individuals who exhibited evidence incomplete suppression on a regimen containing an (23 raltegravir, 6 elvitegravir). Before initiating inhibitor-based regimen, median CD4 T-cell count and plasma HIV RNA levels were 62 cells/mm 4.65 log10 copies/mL,...

ABSTRACT Ibalizumab (formerly TNX-355) is a first-in-class, monoclonal antibody inhibitor of CD4-mediated human immunodeficiency type 1 (HIV-1) entry. Multiple clinical trials with HIV-infected patients have demonstrated the antiviral activity, safety, and tolerability ibalizumab treatment. A 9-week phase Ib study adding monotherapy to failing drug regimens led transient reductions in HIV viral loads evolution HIV-1 variants reduced susceptibility ibalizumab. This report characterizes these...

Microorganisms that colonize the plant rhizosphere can contribute to health, growth and productivity. Although importance of microbiome is known, we know little about underlying mechanisms drive assembly composition. In this study, variation, composition rhizobacterial communities in 11 tomato cultivars, combined with one cultivar seven different sources soil growing substrate, were systematically investigated. The microbiota was dominated by bacteria from phyla Proteobacteria,...

The routine use of phenotypic drug resistance testing in patient management has revealed that many HIV-1 strains possess significantly increased sensitivity, or 'hypersusceptibility' compared with wild-type viruses. This study describes hypersusceptibility to non-nucleoside reverse transcriptase inhibitors (NNRTI) and was designed determine the prevalence viral characteristics associated NNRTI patient-derived Retrospective analyses were performed on a large clinical laboratory dataset...

One hundred thirty-two recipients of blood components that retrospectively tested positive for antibody to human immunodeficiency virus type 1 (anti-HIV-1) were identified. Fourteen (11%) remained seronegative throughout follow-up. Donor and recipient characteristics could have influenced transmission examined. Attributes did not differ infected uninfected recipients. Peripheral mononuclear cells (PBMC) from HIV-1-negative by DNA amplification culture but susceptible in vitro infection....

Eighteen transfusion recipients infected with human immunodeficiency viws type 1 (HIV-1) were followed prospectively their 19 long-term sexual partners from 1986 to 1993 in California, Florida, and New York. Follow-up included clinical, behavioral, immunologic, serologic, virologic evaluations. Two already when seen 18 34 months after contact began following the infectious transfusion. Four of 17 initially seronegative seroconverted during 23 person-years observation. The recipient's...

The emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants is associated with accelerated disease progression. are believed to evolve from CCR5-using variants, but due the extremely low frequency at which transitional intermediate often present, kinetics and mutational pathways involved in this process have been difficult study therefore poorly understood. Here, we used ultra-deep sequencing V3 loop viral envelope combination V3-based coreceptor prediction tools...

The previously reported CXCR4 antagonist KRH-1636 was a potent and selective inhibitor of CXCR4-using (X4) human immunodeficiency virus type 1 (HIV-1) but could not be further developed as an anti-HIV-1 agent because its poor oral bioavailability. Newly KRH-3955 is derivative that bioavailable when administered orally with much more activity than AMD3100 KRH-1636. compound very potently inhibits the replication X4 HIV-1, including clinical isolates in activated peripheral blood mononuclear...

Phytoremediation technology is viewed as a potential solution for addressing soil uranium contamination. Sudan grass (Sorghum sudanense (Piper) Stapf.), noted its robust root structure and resilience to heavy metals, has garnered significant attention. This paper investigates strain of uranium-tolerant bacterium, B6, obtained from the inter-root environment native plants in contaminated with tailings. The bacterium was identified Bacillus cereus. Genomic analyses assessment...

Abstract Aims This study aimed to isolate and identify antifungal metabolites evaluate potential applications for biocontrol. Methods Results Using a bioactivity-guided fractionation approach, we obtained the macrolide metabolite borrelidin from Streptomyces rochei A144, which exhibited significant inhibitory effects on V. mali mycelial growth (EC50 = 22.23 μg mL−1). Scanning transmission electron microscopy analyses revealed that caused damage hyphae, such as breakage, increased swelling...