A swallow challenge medium (10) is thixotropic for easy swallowing and to provide enough viscosity for effective challenge to peristalsis (20) and has high ionic density for effective impedance measurements by contact with electrodes (41-48) positioned in a persons esophagus (E) or oropharynx during swallow testing. The medium (10) also has a high surface tension so as not to adhere to or coat the electrodes (41-48) or probe (12) surfaces. These physical characteristics are stabilized and consistent enough to provide standard for esophageal and/or oropharyngeal function testing and diagnostics.

Exposure to first-generation HIV-1 integrase strand transfer inhibitors (INSTIs), such as raltegravir (RAL) and elvitegravir (EVG), is frequently associated with the selection of resistance-associated mutations (RAMs) at virological failure. Recently developed second-generation INSTIs, such as dolutegravir (DTG; approved by FDA and European Medicines Agency [EMA] in 2013 and 2014, respectively), bictegravir (BIC; approved by FDA and EMA in 2018 as part of a single tablet regimen, including tenofovir alafenamide [TAF] and emtricitabine [FTC]), and cabotegravir (CAB; currently under phase III clinical investigation) have demonstrated a superior genetic barrier to resistance and a variable activity against viruses harboring INSTI resistance mutations selected by RAL and EVG. However, predicting the activity of second-generation INSTIs on HIV-1 variants with different combination of INSTI RAMs is not straightforward. This study aimed at clarifying cross-resistance to DTG, BIC, and CAB in a panel of ...

Bictegravir (BIC) is an investigational, once-daily, unboosted HIV integrase strand transfer inhibitor (INSTI) with potent in vitro activity against most INSTI-resistant variants. BIC is currently in development as a single tablet regimen (STR) coformulated with FTC/TAF for treatment of HIV-1 infection in adults and adolescents. Clinical pharmacology assessments of the PK, ADME and DDI potential were performed.. A single- (SD) and multiple-dose (MD) randomized, double-blind, placebo-controlled (6 active; 2 placebo/cohort) of staggered dose-escalation evaluated SD BIC 5, 25, 50, 100, 300 or 600 mg; or once-daily MD 5, 25, 50, 100 or 300 mg for 14 days (fasted) in healthy volunteers. An ADME/ mass balance study included 8 healthy male subjects dosed with a SD 100 mg plus 100 µCi [14C]-labeled BIC. Blood, urine and feces samples were analyzed for total radioactivity and pooled plasma and excreta samples were radio-profiled. An open-label, six cohort (n=15/cohort), fixed sequence and cross-over ...

HIV-1 integrase (IN) has been validated as an attractive target for the treatment of HIV/AIDS. Several studies have confirmed that the metal binding function is a crucial feature in many of the reported IN inhibitors. To provide new insights on the metal chelating mechanism of IN inhibitors, we prepared a series of metal complexes of two ligands (HL1 and HL2), designed as representative models of the clinically used compounds raltegravir and elvitegravir. Potentiometric measurements were conducted for HL2 in the presence of Mg(II), Mn(II), Co(II), and Zn(II) in order to delineate a metal speciation model. We also determined the X-ray structures of both of the ligands and of three representative metal complexes. Our results support the hypothesis that several selective strand transfer inhibitors preferentially chelate one cation in solution and that the metal complexes can interact with the active site of the enzyme. ...

Bictegravir (formerly GS-9883) is a potent integrase inhibitor under development for the treatment of people with HIV. Bictegravir is made by Gilead Sciences.. In laboratory experiments with cells and HIV, bictegravir can work against many strains of HIV that are resistant to other integrase inhibitors, such as raltegravir (Isentress) and elvitegravir (in Genvoya and Stribild). Bictegravir is also effective against some strains of HIV that are resistant to another integrase inhibitor, dolutegravir (Tivicay and in Triumeq).. In a phase II randomized clinical trial, researchers gave 131 people who had not previously used HIV therapy bictegravir or dolutegravir, each drug taken with a backbone of TAF (tenofovir alafenamide) and FTC (emtricitabine). Both bictegravir- and dolutegravir-containing regimens performed well over 48 weeks, with more than 90% of participants achieving a viral load less than 50 copies/mL. Side effects were common but were mostly mild or moderate. No side effects were graded ...

The first human immunodeficiency virus (HIV) case was reported in the United States in the early 1980s. Many drugs have been discovered to treat the disease but mutations in the virus and resistance to the drugs make development difficult. Integrase is a viral enzyme that integrates retroviral DNA into the host cell genome. Integrase inhibitors are a new class of drugs used in the treatment of HIV. The first integrase inhibitor, raltegravir, was approved in 2007 and other drugs were in clinical trials in 2011. In the 1980s an infectious disease started to plague human civilization. The coexistence of viruses and humans is a fight for survival for both because the invaders can kill the human but in doing so eliminate their own host. The body uses its immune system to protect itself from bacteria, viruses and other disease-causing beings, and when it fails to do so immunodeficiency diseases occur. One such disease is acquired immunodeficiency syndrome (AIDS) which is most commonly a result of an ...

This 2-arm study evaluated the efficacy and safety of Fuzeon with an integrase inhibitor in an expanded access program plus an optimized background antiviral regimen (AVR) in HIV-1 infected patients naive to Fuzeon and an integrase inhibitor. In the first cohort phase of the study (Phase I), eligible patients received Fuzeon 90 mg subcutaneously (SC) twice daily until confirmation of response (min/max = 8/16 weeks). In Phase II, the randomised comparator phase of the study, responders were randomized to receive Fuzeon either 90 mg SC twice a day or 180 mg SC once a day for a further 16 weeks. Non-responders and virological failures were terminated from the study. The anticipated time on study treatment was 3-9 months, and the target sample size was 210 individuals ...

Elvitegravir is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) used for the treatment of HIV-1 infection in antiretroviral treatment-experienced adults. Because integrase is necessary for viral replication, inhibition prevents the integration of HIV-1 DNA into the host genome and thereby blocks the formation of the HIV-1 provirus and resulting propagation of the viral infection. Although available as a single dose tablet, elvitegravir must be used in combination with an HIV protease inhibitor coadministered with ritonavir and another antiretroviral drug. It was developed by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008. The drug gained approval by the U.S. Food and Drug Administration on August 27, 2012 for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild. On September 24, 2014 the FDA approved Elvitegravir (tradename Vitekta) as a single

This clinical study proposes to evaluate the combination of maraviroc with an integrase strand transfer inhibitor (either raltegravir or dolutegravir) in antiretroviral-experienced patients to document the efficacy, safety, and tolerability of this combination in order to provide clinicians with a treatment regimen that minimizes the risk of metabolic complications by avoidance of NRTI/NNRTIs and PIs. The development of an alternative ART regimen which lessens the risk of metabolic complications could improve long-term adherence and reduce the risk of certain co-morbidities associated with long-term ART use. If this new combination is found to be as efficacious as the standard regimen with enhanced tolerability and improved metabolic effects, there is great potential for altering the current practice of HIV medicine ...

September 24, 2014 - The U.S. Food and Drug Administration (FDA) has approved Vitekta (elvitegravir), an integrase strand transfer inhibitor for the combination treatment of human immunodeficiency virus type 1 (HIV-1) infection in ...

E mutations. Among the antiretroviral drugs, integrase inhibitors would be suitable to decrease the archived virus and, if not used as first line, could be used

Specimen collection and processing instructions for medical laboratory test HIV-1 GENOTYPE (RTI, PI, INTEGRASE INHIBITORS) at Geisinger Medical Laboratories

GlaxoSmithKline (GSK) has licensed an anti-HIV integrase inhibitor discovered by the Shionogi Corporation in Japan. Because of these arrangements, this ...

Integrase inhibitors are a type of antiretroviral treatment used to treat HIV. These drugs work by preventing HIV from making an enzyme it needs to spread throughout the body. Theyre often used with other drugs in single-tablet formulas. Learn how these drugs work, what side effects they can cause, and more.

Analysis of eight studies involving 245 people taking oral or injected GSK1265744 confirmed that the long-acting integrase inhibitor is well tolerated and ...

Thanks for your post and thoughts. I think that all of Dr. Hos comments are accurate on this point. Integrase inhibitors (INIs) are attractive because they inhibit a new target, thus, patients...

Adult and adolescent treatment guidelines of the U.S. Department of Health and Human Services designate the coformulation elvitegravir/cobicistat/emtricitabine/TDF as a recommended regimen for initial treatment of HIV infection, for patients whose estimated creatinine clearance is ≥70 mL/min, and the coformulation elvitegravir/cobicistat/emtricitabine/TAF as a recommended regimen for patients whose estimated creatinine clearance is ≥30 mL/min.. Elvitegravir has been studied primarily in initial therapy in adults.. In a randomized, placebo-controlled Phase 3 study in antiretroviral-naive adults, the fixed-dose coformulation of elvitegravir/cobicistat/emtricitabine/TDF was compared with efavirenz/tenofovir/emtricitabine.(1) By intention-to-treat snapshot analysis, 88% of elvitegravir + cobicistat recipients and 84% of efavirenz recipients had HIV RNA levels of ,50 copies/mL at 48 weeks; the difference was not statistically significant. Responses in the two groups also were similar in ...

From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. ...

Cabotegravir is an investigational drug that is being studied for the treatment and prevention of HIV infection. Cabotegravir belongs to a class (group) of HIV drugs called integrase inhibitors. Integrase inhibitors block an HIV enzyme called integrase. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) By blocking integrase, integrase inhibitors prevent HIV from multiplying and can reduce the amount of HIV in the body. Cabotegravir does not require boosting with an additional drug. Two forms of cabotegravir are being studied: tablets that are taken by mouth (known as oral cabotegravir or oral CAB) and a long-acting injectable form that is injected into the muscle (known as cabotegravir LA or CAB LA; LA stands for long-acting). (A long-acting drug formulation works over a long period of time. Using this type of drug might mean that the drug could be taken less often, making a treatment or prevention regimen simpler to take.) Cabotegravir is in Phase-III ...

A group of drugs that share common properties, including a similar mechanism of action, chemical structure, or approved use. Antiretroviral (ARV) HIV drugs are classified into six drug classes based on how each drug interferes with the HIV life cycle. These six classes include the nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion and entry inhibitors, pharmacokinetic enhancers, and integrase strand transfer inhibitors (INSTIs).

FOSTER CITY, Calif.-(BUSINESS WIRE)-Gilead Sciences, Inc. (Nasdaq:GILD) today announced that four Phase 3 studies evaluating a fixed-dose combination of bictegravir (50mg) (BIC), a novel investigational integrase strand transfer inhibitor (INSTI), and emtricitabine/tenofovir alafenamide (200/25mg) (FTC/TAF) for the treatment of HIV-1 infection met their primary objectives of non-inferiority. Three of the …. ...

A curated database containing nearly all published HIV RT and protease sequences: a resource designed for researchers studying evolutionary and drug-related variation in the molecular targets of anti-HIV therapy.

Bictegravir-containing regimens performed well over 48 weeks, with more than 90% of participants achieving a viral load less than 50 copies/mL.

ROME -- The once-daily investigational integrase inhibitor elvitegravir was shown to be noninferior to the twice-daily raltegravir (Isentress) in treatment of therapy-experienced, HIV-infected individ

FDA has approved two new HIV-1 cocktail drugs: elvitegravir (Vitekta, Gilead), an integrase inhibitor and cobicistat (Tybost, Gilead), a protease-inhibitor booster.

Biological Description: MK-2048 is a potent inhibitor of integrase and INR263K with IC50 of 2.6 nM and 1.5 nM, respectively.IC50 Value: 2.6 nM for HIV IntegraseTarget: HIV IntegraseMK-2048 is a second generation integrase inhibitor, intended to be used against HIV infection. MK ...

Everything you need to know about protease inhibitors, entry inhibitors, integrase inhibitors, NRTIs and NNRTIs. Focus on HAART and practice answering clinically relevant and high yield study questions.

Osamuede Ede Osemwota, a senior biochemistry and French major at DePauw University, will spend the next year in France researching an HIV-1 integrase inhibitor through an international graduate study and research grant awarded via the 2006-07 Fulbright U.S. Student Program competition. Fulbright student grants aim to increase mutual understanding among nations through educational and cultural exchange while serving as a catalyst for long-term leadership development.

Tivicay is a new integrase inhibitor made by GlaxoSmithKline which was shown to be slightly better than Gileads Atripla in reducing viral load in HIV infected patients after 48 weeks.

AIMS S/GSK1349572 can be an unboosted, once daily, next era integrase inhibitor with potent activity, low pharmacokinetic (PK) variability and a book resistance profile. rate of recurrence was ocular icterus, noticed just during mix of S/GSK1349572 and ATV or ATV/RTV. Co-administration with ATV/RTV led to improved plasma S/GSK1349572 region beneath the concentrationCtime curve throughout a […]. ...

This class of antiretroviral (ARV) drugs inhibits integrase, the viral enzyme that catalyzes the two-step process of insertion of HIV DNA into the genome of the human cell. Integrase catalyzes a preparatory step that excises two nucleotides from one strand at both ends of the HIV DNA and a final strand transfer step that inserts the viral DNA into the exposed regions of cellular DNA. The integrase inhibitor drug class targets this second step in the integration process. Integration is required for the stable maintenance of the viral genome as well as for efficient viral gene expression and replication. Integrase also affects reverse transcription and viral assembly. Host cells lack the integrase enzyme. Because HIV integrase represents a distinct therapeutic target, integrase inhibitors would be expected to maintain activity against HIV that is resistant to other classes of ARV drugs.. Dolutegravir (Tivicay, DTG) ...

At the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, 48-week results from a somewhat small Phase 2 study in people new to treatment showed that the Gilead Sciences experimental integrase inhibitor bictegravir suppressed HIV levels as well as ViiVs integrase in...

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Vitetkta (elvitegravir) is an integrase inhibitor-class drug used in the treatment of HIV-1 infection for patients previously exposed to therapy.

Acta Biologiae Experimentalis sinica Vol.38,No.2 April 2005 The influnce of glutamic acid transfer inhibitor to organotypic culture spinal cord Xiao Xiangjian; Wang Xiaojuan; Wang Liqin Read more: en/upfiles/pdf/The_influnce_of_glutamic_acid_transfer

The purpose of this study is to evaluate if there are significant drug-drug interactions between cobicistat-boosted elvitegravir and 800mg darunavir once daily

This study has assessed the experience with Elvitegravir/emtricitabine/tenofovir-disoproxil-fumarate/cobicistat (Stribild) in a Spanish region in HIV-infected

Genetic diversity on the integrase region of the pol gene among HIV type 1-infected patients naive for integrase inhibitors in Sao Paulo City, Brazil ...

In 2019, there are currently 13 single-tablet regimens (STRs) in the U.S. market, of which six contain an integrase inhibitor. Each contains two to four HIV medications (the fourth being a booster such as ritonavir or cobicistat). STRs are much easier than taking 10 or 20 or even five pills daily. But many PLWHA (especially those who were diagnosed in the 1980s and 90s) experience pill fatigue. Plain and simple, they are sick and tired of taking pills every day year after year and being told they would have to take them every day for the rest of their lives. Also, newly diagnosed and otherwise healthy PLWHAs have to adjust to the new routine of taking a daily medication, which can be a huge challenge. But a possible solution may be coming.. Its expected that the U.S. Food and Drug Administration (FDA) will approve the first long-acting injectable form of HIV combination therapy before the end of 2019. The first two drugs that are coming are injectable long-acting cabotegravir (an integrase ...

Pada artikel bagian 3 sudah dibahas jenis ARV dari golongan Protease Inhibitors (PIs), Fusion Inhibitors, CCR5 Antagonist. Di bagian 4 kita akan membahas jenis lainnya: 6. Integrase Inhibitors Obat-obat jenis ini menghentikan HIV dari membuat salinan dirinya sendiri dengan memblokir protein kunci yang memungkinkan virus untuk menempatkan DNA-nya ke dalam DNA…

Preliminary analysis of an ongoing clinical birth surveillance study suggested increased risk of NTDs in newborns from mothers taking dolutegravir at the time of conception (Zash et al., 2018). Dolutegravir is an integrase inhibitor for the treatment of HIV, a drug class that also includes cabotegravir, bictegravir, raltegravir, and elvitegravir (Han et al., 2017). Folate deficiency increases the incidence rate of NTDs (Daly et al., 1995; Botto et al., 1999; Crider et al., 2014; Kancherla et al., 2018). Folate relies on transport via PCFT for intestinal absorption, FRα-mediated endocytosis along with transport by PCFT and RFC for tissue distribution, including to the fetus, and renal sparing via active tubular reabsorption after extensive glomerular filtration (Fig. 1, Solanky et al., 2010; Zhao et al., 2011).. The aim of the present work was to determine whether dolutegravir and other integrase inhibitor drugs may be clinically relevant inhibitors of the three major folate transport pathways, ...

Prior to WuXi, John spent over 20 years at Merck Research Laboratories, contributing to the discovery efforts of many programs, from target validation & lead identification to lead optimization & early development. This includes HIV-1 non-nucleoside reverse transcriptase inhibitors, ras-farnesyl protein transferase inhibitors, fibrinogen receptor antagonists, HIV integrase strand transfer inhibitors, HIV RNase H inhibitors, gamma secretase inhibitors, etc. John received the Distinguished Scientific Award from the inaugural Merck West Point Basic Research Reward and Recognition Forum for his work on HIV integrase inhibitors, and recently, John received the Heroes of Chemistry Award from the American Chemical Society (September 2013) for his contribution to the discovery and development of Isentress, the first HIV integrase inhibitors approved for treatment of AIDS (2007). This week we sat down with John to discuss his career and thoughts on the industry.. How did you get started as a medicinal ...

Genotype-defined resistance to antiretrovirals supposedly predicts future virological failure. Findings from clinical studies, including the 144-week results from the EARNEST trial, challenge this decades-long dogma, certainly when it comes to nucleoside analogues.. The World Health Organisation (WHO) currently recommends second-line treatment with two nucleoside reverse-transcriptase inhibitors (NRTIs) and a boosted protease inhibitor. However, there is evidence for widespread resistance to NRTIs after virological failure of first-line treatment in low-income countries, which might limit future treatment options.. The EARNEST trial was set up to evaluate alternatives for second-line treatment, including the current WHO recommendation, which involves sequencing without genotype guidance using virological, immunological, and clinical failure. The novel combination of two drug classes, the integrase inhibitor raltegravir with the boosted protease inhibitor ritonavir-boosted lopinavir (LPV/r), was ...

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the Phase III clinical trial of its investigational antiretroviral agent elvitegravir, a novel oral

Easy to read patient leaflet for Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide. Includes indications, proper use, special instructions, precautions, and possible side effects.

The FDA has approved a dual therapy for HIV from GlaxoSmithKlines ViiV joint venture with Johnson & Johnson, which is expected to mount a strong challenge to rival treatments from Gilead.. The US regulator gave a green light to Juluca, which combines ViiVs integrase inhibitor Tivicay (dolutegravir) with a non-nucleoside reverse transcriptase inhibitor Edurant (rilpivirine) developed by J&Js Janssen unit, both of which are already approved for marketing separately.. The new regimen is the first, complete, single-pill, two-drug regimen for the treatment of HIV, rather than the standard three or more drugs, according to Janssen and GSK, and has been approved as a new option for people with HIV who have been virally suppressed on their current regimen for at least six months.. Patients considering Juluca as a treatment option should also have no history of HIV treatment failure and no known viral mutations associated with resistance to either of the drugs in the regimen, according to the ...

Investigation of novel lipid-functionalized PNA monomers as potential HIV-1 non-nucleoside reverse transcriptase and/or integrase inhibitors.

Electrochemical DNA (E-DNA) sensors have emerged as a promising class of biosensors capable of detecting a wide range of molecular analytes (nucleic acids, proteins, small molecules, inorganic ions) without the need for exogenous reagents or wash steps. In these sensors, a binding-induced conformational change in an electrode-bound probe (a target-binding nucleic acid or nucleic-acid-peptide chimera) alters the location of an attached redox reporter, leading to a change in electron transfer that is typically monitored using square-wave voltammetry. Because signaling in this class of sensors relies on binding-induced changes in electron transfer rate, the signal gain of such sensors (change in signal upon the addition of saturating target) is dependent on the frequency of the square-wave potential pulse used to interrogate them, with the optimal square-wave frequency depending on the structure of the probe, the nature of the redox reporter, and other features of the sensor. Here, we show that, ...

Abcam provides specific protocols for Anti-HIV1 integrase antibody [IN-2] (ab66645) : Western blot protocols, Immunoprecipitation protocols…

UNLABELLED: The R263K substitution in integrase has been selected in tissue culture with dolutegravir (DTG) and has been reported for several treatment-experienced individuals receiving DTG as part of salvage therapy. The R263K substitution seems to be incompatible with the presence of common resistance mutations associated with raltegravir (RAL), a different integrase strand transfer inhibitor (INSTI). T66I is a substitution that is common in individuals who have developed resistance against a different INSTI termed elvitegravir (EVG), but it is not known whether these two mutations might be compatible in the context of resistance against DTG or what impact the combination of these substitutions might have on resistance against INSTIs. E138K is a common secondary substitution observed with various primary resistance substitutions in RAL- and EVG-treated individuals. Viral infectivity, replicative capacity, and resistance against INSTIs were measured in cell-based assays. Strand transfer and 3 ...

Cabotegravir, also known as S/GSK1265744 or GSK744, is potent HIV integrase inhibitor under development for the treatment of HIV infection. Cabotegravir has a carbamoyl pyridone structure similar to dolutegravir.

Key to Acronyms: 3TC = lamivudine; ABC = abacavir; Al = aluminum; ARV = antiretroviral; ATV = atazanavir; BIC = bictegravir; Ca = calcium; COBI = cobicistat; CYP = cytochrome P; DOR = doravirine; DRV = darunavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; Fe = iron; FPV = fosamprenavir; FTC = emtricitabine; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; MATE = multidrug and toxin extrusion transporter; Mg = magnesium; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitors; NRTI = nucleoside reverse transcriptase inhibitors; NVP = nevirapine; OCT2 = organic cation transporter 2; OATP = organic anion-transporting polypeptide; PK = pharmacokinetic; PI = protease inhibitor; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; T-20 = enfuvirtide; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TPV = tipranavir; UGT = uridine diphosphate glucuronosyltransferase; ZDV = zidovudine; Zn = zinc ...

RESULTS: Antiretroviral therapy is recommended for all adults with HIV infection. Evidence for benefits of treatment and quality of available data increase at lower CD4 cell counts. Recommended initial regimens include 2 nucleoside reverse transcriptase inhibitors (NRTIs; abacavir/lamivudine or tenofovir disoproxil fumarate/emtricitabine) and a third single or boosted drug, which should be an integrase strand transfer inhibitor (dolutegravir, elvitegravir, or raltegravir), a nonnucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine) or a boosted protease inhibitor (darunavir or atazanavir). Alternative regimens are available. Boosted protease inhibitor monotherapy is generally not recommended, but NRTI-sparing approaches may be considered. New guidance for optimal timing of monitoring of laboratory parameters is provided. Suspected treatment failure warrants rapid confirmation, performance of resistance testing while the patient is receiving the failing regimen, and evaluation of ...

The spectrum of anti-HIV drugs was recently extended by a new class of drugs, the integrase inhibitors. The first drug of this class that received FDA approval is Raltegravir. Clinical data show that when previously untreated patients start treatment on Raltegravir, their viral load declines more rapidly than it does in patients who take instead the reverse-transcriptase inhibitor Efavirenz. This spring, Antiviral Therapy published a modeling study by [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980788/ Sedaghat et al.] that discusses the possible mechanisms responsible for this accelerated decline in viral load. The study argues that the accelerated decline is likely not caused by greater antiviral efficiency of Raltegravir compared to Efavirenz. Instead, because Raltegravir acts later in the viral life cycle than Efavirenz, at the beginning of Raltegravir therapy fewer cells have progressed to a state where the drug can not inhibit virus production, and hence the viral load declines faster. ...

The spectrum of anti-HIV drugs was recently extended by a new class of drugs, the integrase inhibitors. The first drug of this class that received FDA approval is Raltegravir. Clinical data show that when previously untreated patients start treatment on Raltegravir, their viral load declines more rapidly than it does in patients who take instead the reverse-transcriptase inhibitor Efavirenz. This spring, Antiviral Therapy published a modeling study by [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980788/ Sedaghat et al.] that discusses the possible mechanisms responsible for this accelerated decline in viral load. The study argues that the accelerated decline is likely not caused by greater antiviral efficiency of Raltegravir compared to Efavirenz. Instead, because Raltegravir acts later in the viral life cycle than Efavirenz, at the beginning of Raltegravir therapy fewer cells have progressed to a state where the drug can not inhibit virus production, and hence the viral load declines faster. ...

Detailed drug Information for elvitegravir, cobicistat, emtricitabine, and tenofovir. Includes common brand names, drug descriptions, warnings, side effects and dosing information.

Antiretroviral pre-exposure prophylaxis has huge potential for reducing the rates of new HIV infections in at risk populations. Oral and vaginal antiretroviral formulations have been evaluated in multiple Phase 2B/3 effectiveness trials and there is clear evidence that these products work when used. The converse is also true; antiretrovirals do not work when they are not used. As a consequence, long-acting (LA) injectable and implantable antiretroviral formulations are being developed for the prevention of HIV infection. The two lead products are the non-nucleoside reverse transcriptase inhibitor rilpivirine and the integrase inhibitor cabotegravir. It is hoped that the use of LA antiretroviral PrEP will reduce the burden of product adherence associated with the use of oral and topical products and improve the level of HIV prevention associated with this form of PrEP. Although LA products have clear promise for HIV prevention, there are also challenges to consider. There are concerns about the ...

Virtually all people had treatment experience with the NRTI, NNRTI and protease inhibitor drug classes. With integrase inhibitors, 75% of the randomised group and 95% of the immediate-treatment group had experience. Thirty-nine per cent in the randomised group and 69% in the immediate-treatment group had taken the fusion inhibitors T-20 or T-1249. Twenty-six per cent and 40% respectively had taken a CCR5 inhibitor like maraviroc.. During the eight days of randomisation, people on fostemsavir experienced an 0.8 log copies/ml drop (about a 6.5-fold drop) in viral load compared with an 0.2 log drop in those on placebo.. At week 48, in a strict analysis that defined any change in OBR as a regimen failure, a viral load below 40 copies/ml on their regimen was achieved by 54% of people in the randomised group and 38% of those in the immediate-treatment group.. Black participants in the study did somewhat better, with 65% with a viral load below 40 copies/ml vs 50% of other people, as did women (61% ...

Dr. Kathleen Kate Rubins conducted her undergraduate research on HIV-1 integration in the Infectious Diseases Laboratory at the Salk Institute for Biological Studies. She analyzed the mechanism of HIV integration, including several studies of HIV-1 Integrase inhibitors and genome-wide analyses of HIV integration patterns into host genomic DNA. She obtained her Ph.D. from Stanford University and, with the U.S. Army Medical Research Institute of Infectious Diseases and the Centers for Disease Control and Prevention, Dr. Rubins and colleagues developed the first model of smallpox infection. She also developed a complete map of the poxvirus transcriptome and studied virus-host interactions using both invitro and animal model systems.. Dr. Rubins then accepted a Fellow/Principal Investigator position at the Whitehead Institute for Biomedical Research (MIT/Cambridge, Massachusetts) and headed a lab of 14 researchers studying viral diseases that primarily affect Central and West Africa. She traveled ...

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.. Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.. ...