• Access to second-line ART regimens in developing countries is problematic, mainly because of the expense of HIV protease inhibitors (PIs). (lww.com)
  • Data are scarce regarding the incidence of neuropsychiatric events (NPEs) in people living with human immunodeficiency virus (HIV)-1 taking integrase inhibitor (INI)- or protease inhibitor (PI)-based regimens. (psychiatrist.com)
  • 1,5,8 Additionally, neuropsychiatric adverse events (AEs) leading to discontinuations have been seen in phase 3 studies of integrase inhibitor (INI)-based regimens. (psychiatrist.com)
  • Lathouwers E, Wong EY, Luo D, Seyedkazemi S, De Meyer S, Brown K. HIV-1 resistance rarely observed in patients using darunavir once-daily regimens across clinical studies. (ajmc.com)
  • 1 Lathouwers and colleagues sought to analyze the outcomes from 7 phase 2 and phase 3 clinical trials that investigated darunavir 800-mg once-daily-containing HAART regimens to determine the observed rates of post-baseline resistance in patients with HIV-1. (ajmc.com)
  • Dolutegravir-based treatment in PLHIV with pre-existing nucleoside reverse transcriptase inhibitor-mutations was non-inferior to protease inhibitor-based regimens. (lu.se)
  • The prevalence of drug resistance is high among children with HIV, making it critical that children receive regimens that are active against drug-resistant virus and that clinicians have timely viral load information to enable a switch in treatment before high-level drug resistance emerges. (aidsmap.com)
  • Although all participants had used - and a majority had developed resistance to - at least two antiretroviral drug classes, they were able to construct viable regimens using a ritonavir-boosted protease inhibitor and an active third agent such as etravirine ( Intelence ), maraviroc ( Celsentri or Selzentry ) or a nucleoside/nucleotide reverse transcriptase inhibitor. (aidsmap.com)
  • Telaprevir, a first generation orally bioavailable inhibitor of the nonstructural 3/4A HCV protease, shows significantly higher rates of SVR than standard care of PEG-IFN α and ribavirin in patients with HCV G1 disease when given for 12 weeks in combination with regimens of PEG-IFN α plus ribavirin lasting 12, 24, or 48 weeks [ 4 - 6 ]. (hindawi.com)
  • The mean time on ART was 75.5 months (95% confidence interval [CI]: 69.0-81.9 months), and 93.7% of the patients were receiving non-nucleoside reverse transcriptase inhibitor-based regimens. (who.int)
  • It is a combination of nirmatrelvir, a protease inhibitor targeted to SARS-CoV-2's 3C-like protease, and ritonavir to inhibit nirmatrelvir's metabolism. (wikipedia.org)
  • Protease inhibitors also are used to treat Hepatitis C. Researchers are investigating the use of protease inhibitors developed for HIV treatment as anti-protozoals for use against malaria and gastrointestinal protozoal infections: A combination of ritonavir and lopinavir was found to have some effectiveness against Giardia infection. (wikipedia.org)
  • See section 4.4 for advice on darunavir/ritonavir treatment in protease inhibitor-experienced patients when genotype testing is not available. (who.int)
  • This study evaluated the safety and efficacy of switching HIV-infected patients with stable viral suppression on nonnucleoside reverse transcriptase inhibitor/nucleoside reverse transcriptase inhibitor (NNRTI/NRTI) therapy to lopinavir/ritonavir (LPV/r) monotherapy. (researchgate.net)
  • 1 The US Department of Health and Human Services (HHS) and the European AIDS Clinical Society recommend initial treatment of HIV-1 infection with once-daily boosted darunavir 800 mg (with ritonavir or cobicistat as additional boosters) combined with 2 nucleos(t)ide reverse transcriptase inhibitors (N[t]RTIs). (ajmc.com)
  • Gilead Sciences next-generation integrase inhibitor elvitegravir is used with a boosting agent - either ritonavir ( Norvir ) or Gilead's novel pharmacoenhancer cobicistat - to enable once-daily dosing. (aidsmap.com)
  • Combination therapy has been shown to dramatically reduce the likelihood of drug resistance (many drug-resistant mutations are mutually exclusive) and to suppress viral replication to the point that progression to AIDS is significantly slowed. (medscape.com)
  • Antiviral-resistance mutations often affect more than one drug simultaneously because of similar development pipelines and the ultimate molecular structure of the drug, and combination choices should account for this possibility. (medscape.com)
  • HIV protease inhibitors against the viral protease are often hampered by drug resistance mutations in protease and in the viral substrate Gag. (a-star.edu.sg)
  • In order to successfully inhibit Gag, understanding of its drug resistance mutations and the elicited structural changes on protease binding needs to be investigated. (a-star.edu.sg)
  • While mutations on Gag have already been mapped to protease inhibitor resistance, there remain many mutations, particularly the non-cleavage mutations, that are not characterized. (a-star.edu.sg)
  • Through structural studies to unravel how Gag mutations contributes to protease drug resistance synergistically, it is thus possible to glean insights to design novel Gag inhibitors. (a-star.edu.sg)
  • However, one of the limiting factors of the effectiveness of antiviral therapy with protease inhibitors (PIs) is the emergence of resistance caused by point mutations. (fiocruz.br)
  • Characterization of naturally occurring protease inhibitor-resistance mutations in genotype 1b hepatitis C virus patients. (bvsalud.org)
  • PI-resistance-associated NS3 mutations exist in a substantial proportion of untreated HCV-1b-infected patients . (bvsalud.org)
  • The impact of these mutations in the treatment of PIs is unclear, but clinicians should pay attention to avoid further development of PI resistance. (bvsalud.org)
  • Using HIV-1 as a model system, we optimized and validated PANDAA to detect HIV drug resistance mutations (DRMs). (nature.com)
  • Exposure to 810 induced mutations in the catalytic core of HIV integrase, resulting in 1.6-fold to 9-fold resistance. (natap.org)
  • Successful highly active antiretroviral therapy (HAART) for the treatment of HIV-1 infection is contingent on limiting or avoiding the development of resistance-associated mutations (RAMs). (ajmc.com)
  • This 2-drug long-acting injectable antiretroviral-based regimen for maintenance of viral load suppression consists of Rilpivirine (a non-nucleoside reverse transcriptase inhibitor) and Cabotegravir (an integrase inhibitor). (theseoultimes.com)
  • Patients were also tested for insulin resistance, glucose intolerance, hyperlipidaemia, TNF- and TNF receptor levels before and after stopping PIs. (natap.org)
  • Insulin resistance ( IR ) is a pathological condition in which cells either fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia . (wikipedia.org)
  • In states of insulin resistance, the same amount of insulin does not have the same effect on glucose transport and blood sugar levels. (wikipedia.org)
  • There are many causes of insulin resistance and the underlying process is still not completely understood. (wikipedia.org)
  • Risk factors for insulin resistance include obesity , sedentary lifestyle , family history of diabetes, various health conditions, and certain medications. (wikipedia.org)
  • Insulin resistance is considered a component of the metabolic syndrome . (wikipedia.org)
  • There are multiple ways to measure insulin resistance such as fasting insulin levels or glucose tolerance tests, but these are not often used in clinical practice. (wikipedia.org)
  • Insulin resistance can be improved or reversed with lifestyle approaches, such as exercise and dietary changes. (wikipedia.org)
  • There are a number of risk factors for insulin resistance, including being overweight or obese or having a sedentary lifestyle . (wikipedia.org)
  • [1] Various genetic factors can increase risk, such as a family history of diabetes, and there are some specific medical conditions associated with insulin resistance, such as polycystic ovary syndrome . (wikipedia.org)
  • Dietary factors are likely to contribute to insulin resistance. (wikipedia.org)
  • Foods that have independently been linked to insulin resistance include those high in sugar with high glycemic indices , low in omega-3 and fiber, and which are hyperpalatable which increases risk of overeating. (wikipedia.org)
  • The percentage of polyunsaturated fatty acids (PUFAs) is inversely correlated with insulin resistance. (wikipedia.org)
  • [3] It is hypothesized that increasing cell membrane fluidity by increasing PUFA concentration might result in an enhanced number of insulin receptors, an increased affinity of insulin to its receptors, and reduced insulin resistance. (wikipedia.org)
  • Vitamin D deficiency has also been associated with insulin resistance. (wikipedia.org)
  • Sedentary lifestyle increases the likelihood of development of insulin resistance. (wikipedia.org)
  • Studies have consistently shown that there is a link between insulin resistance and circadian rhythm, with insulin sensitivity being higher in the morning and lower in the evening. (wikipedia.org)
  • A mismatch between the circadian rhythm and the meals schedule, such as in circadian rhythm disorders , may increase insulin resistance. (wikipedia.org)
  • Some medications are associated with insulin resistance including corticosteroids , protease inhibitors (type of HIV medication), [11] and atypical antipsychotics . (wikipedia.org)
  • Being exposed to light during sleep has been shown to cause insulin resistance and increase heart rate. (wikipedia.org)
  • Many hormones can induce insulin resistance including cortisol , [14] growth hormone , and human placental lactogen . (wikipedia.org)
  • Cortisol counteracts insulin and can lead to increased hepatic gluconeogenesis , reduced peripheral utilization of glucose, and increased insulin resistance. (wikipedia.org)
  • Incidence of type 2 diabetes and insulin resistance was high in the ageing HIV population. (lu.se)
  • In the early 2000s, Mueckler's lab investigated how HIV protease inhibitor therapy could cause insulin resistance , among other side effects. (the-scientist.com)
  • Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. (msdmanuals.com)
  • Metabolic changes include the increase of serum lipids and peripheral insulin resistance resulting in DM 9,12 . (bvsalud.org)
  • Insulin resistance (IR) is common in HIV-seropositive patients, particularly among those receiving protease inhibitor (PI) and is more prevalent among those with lipoatrophy or fat accumulation in the visceral region. (bvsalud.org)
  • Maraviroc tablets are contraindicated in patients with severe renal impairment or end-stage renal disease (ESRD) (CrCl less than 30 mL per minute) who are concomitantly taking potent CYP3A inhibitors or inducers. (drugs.com)
  • To understand and combat the HIV-1 Protease drug resistance at the molecular level to design potent inhibitors. (umassmed.edu)
  • AIMS: BI201335 is a highly specific and potent HCV protease inhibitor. (druglib.com)
  • See the articles matrix metalloproteinase inhibitor (-mastat) and proteasome inhibitor (-zomib). (wikipedia.org)
  • For example, a peptide-aldehyde proteasome inhibitor derived from a Chinese medicinal plant has been patented to enhance control of deltamethrin-resistant diamond-back moth larvae. (soci.org)
  • The aim of this study was to determine the prevalence of resistance-associated substitutions (RASs) in HCV NS3 gene in patients infected with genotype 1 before therapy with simeprevir. (fiocruz.br)
  • HA719 trade name] is used for protease inhibitor-experienced patients when HIV-1 genotype testing is available. (who.int)
  • Potency, safety, and pharmacokinetics of the NS3/4A protease inhibitor BI201335 in patients with chronic HCV genotype-1 infection. (druglib.com)
  • In May 2011, the HCV NS3/4A protease inhibitors boceprevir and telaprevir received FDA approval for patients infected with HCV genotype 1. (medscape.com)
  • A third protease inhibitor, simeprevir, received FDA approval in November 2013 for use in patients infected with HCV genotype 1. (medscape.com)
  • Presence of baseline resistance-associated substitutions (RAS) in the serine protease domain of HCV NS3 was analyzed by nucleotide sequencing followed by amino acid deduction. (fiocruz.br)
  • While two of the single substitutions (E166A and L167F) provide low-level resistance to the inhibitors in a biochemical assay, the triple mutant results in the highest levels of resistance (6- to 72-fold). (biorxiv.org)
  • Structural biology analysis indicates that the different substitutions reduce the number of inhibitor/enzyme interactions while the binding of the substrate is maintained. (biorxiv.org)
  • Ultra-Deep Genomic Sequencing of HCV NS5A Resistance-Associated Substitutions in HCV/HIV Coinfected Patients. (uc.edu)
  • This study improves the knowledge of genetic barrier for resistance to PIs involving RASs in chronically infected patients and its possible impact on an unsuccessful treatment outcome, information that might be crucial to upcoming decisions of incorporation of new DAAs in Brazilian guidelines of antiviral therapy against HCV infection. (fiocruz.br)
  • Patients with resistance to antiretroviral drugs. (cdc.gov)
  • Protease inhibitor (PI)-resistant hepatitis C virus (HCV) variants may be present in substantial numbers in PI-untreated patients according to recent reports . (bvsalud.org)
  • Two patients were withdrawn with virologic failure but demonstrated no evidence of virologic resistance. (researchgate.net)
  • To determine whether the metabolic and morphological abnormalities seen in patients with lipodystrophy (LD) are reversed by stopping protease inhibitors (PIs). (natap.org)
  • If patients with severe renal impairment or ESRD receiving maraviroc (without concomitant CYP3A inducers or inhibitors) experience postural hypotension, the dose of maraviroc should be reduced from 300 mg twice daily to 150 mg twice daily. (drugs.com)
  • Patients who were designated as experiencing PDVF underwent resistance testing, apart from those in MONET and PROTEA, in whom any sample that exceeded the viral load threshold was tested for resistance. (ajmc.com)
  • In a virology research environment, the study of viral quasispecies in infected patients is essential for understanding pathways to resistance and can substantially improve treatment. (biomedcentral.com)
  • Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus-infected patients. (mpg.de)
  • 1 log(10) from nadir) were seen in most patients on monotherapy and were caused by NS3/4A variants (R155K, D168V) conferring in vitro resistance to BI201335. (druglib.com)
  • Antiretroviral drug resistance has long challenged patients and providers on the path to viral suppression. (primeinc.org)
  • Prezcobix (darunavir and cobicistat) is a combination of a human immunodeficiency virus ( HIV -1) protease inhibitor and a CYP3A inhibitor and is indicated for the treatment of HIV-1 infection in adult patients. (rxlist.com)
  • ABSTRACT In order to define the protein expressional changes related to the process of meglumine antimoniate resistance in anthroponotic cutaneous leishmaniasis (CL), we performed a comparative proteomics analysis on sensitive and resistant strains of Leishmania tropica isolated from Iranian CL patients. (who.int)
  • Therapy should involve combinations of drugs-two nucleoside-analogue reverse-transcriptase inhibitors combined with either a protease inhibitor (PI) or a non-nucleoside-analogue reverse-transcriptase inhibitor. (medscape.com)
  • Both artemether and lumefantrine are metabolized by hepatic cytochrome P450 (CYP450) enzymes which metabolize the protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) used for HIV treatment. (bvsalud.org)
  • Integrase strand transfer inhibitors (INSTIs) block integrase, which is an HIV enzyme that the virus uses to insert its genetic material into a cell that it has infected. (aidsmap.com)
  • CCR5 antagonists and post-attachment inhibitors block different molecules on the CD4 cells. (medlineplus.gov)
  • Protease inhibitors were the second class of antiretroviral drugs developed. (wikipedia.org)
  • Ending 2 years of troubling silence since this group first described the antiretroviral activity of diketobutanoic acids (DKAs) that specifically and potently inhibit the critical strand transfer step of the integration of the HIV provirus into the human genome, Hazuda and Young drew back the curtain to reveal oral integrase inhibitors ready for Phase I human study. (natap.org)
  • HIV integrase inhibitors prevent the virus from inserting its genetic material into a host cell, a necessary step for viral replication. (aidsmap.com)
  • Protease inhibitors (PIs) are medications that act by interfering with enzymes that cleave proteins. (wikipedia.org)
  • Alternatively, the protease enzymes may be inhibited, or blocked, using RNA interference (RNAi), a method gaining popularity for future pest management. (soci.org)
  • Cobicistat is a mechanism-based inhibitor of cytochrome P450 (CYP) enzymes of the CYP3A family. (rxlist.com)
  • A cysteine protease inhibitor drug was found to cure Chagas disease in mice. (wikipedia.org)
  • Phytocystatins, inhibitors of cysteine proteinases, are found in a number of plants where they may play a role in defense against pests and pathogens. (usda.gov)
  • HIVers taking the protease inhibitor Reyataz might want to kick their smoking habit and stop using marijuana, according to a study presented at the 2009 Interscience Conference on Antimicrobial Agents and Chemotherapy. (hivplusmag.com)
  • 50% of the tobacco users and 36% of marijuana users had Reyataz levels below that which effectively suppresses HIV and at which drug resistance can develop. (hivplusmag.com)
  • These results show that cystatins have the potential to confer resistance to multiple diseases of alfalfa. (usda.gov)
  • Previous study findings have demonstrated that darunavir has a high genetic barrier to the development of resistance, with virologic efficacy shown to be compromised only when 3 or more darunavir RAMs are present in the background of approximately 14 to 15 International Antiviral Society-USA protease inhibitor RAMs. (ajmc.com)
  • Lower efficacy for protease inhibitors was not due to lower adherence to treatment. (lu.se)
  • The sole approved drug in this class, raltegravir, has demonstrated long-term efficacy and minimal toxicity, though it has a relatively low barrier to resistance. (aidsmap.com)
  • It was also fueled by the fact that a lot of those early drugs, especially in the 1990s and early 2000s, were quite toxic - drugs like zidovudine (AZT) , stavudine (d4T), didanosine (ddI) , and the early protease inhibitors . (medscape.com)
  • The participants who failed the regimen developed resistance for both Cabotegravir and Rilpivirine. (theseoultimes.com)
  • And we do have now, Cabotegravir single tablet protease inhibitor combination that can be used if one fails on Cabotegravir/ Rilpivirine, said Orkin. (theseoultimes.com)
  • These protease inhibitors prevent viral replication by selectively binding to viral proteases (e.g. (wikipedia.org)
  • Islatravir is a nucleoside transcription translocation inhibitor, it has a long half life, inhibits viral replication, and its multiple mechanisms of action contribute to its high potency and high barrier to resistance, including drug resistant viruses. (theseoultimes.com)
  • Saskova KG, Kozisek M, Rezacova P, Brynda J, Yashina T, Kagan RM, Konvalinka J. Molecular characterization of clinical isolates of human immunodeficiency virus resistant to the protease inhibitor darunavir. (proteopedia.org)
  • Protease inhibitors can cause a syndrome of lipodystrophy, hyperlipidemia, diabetes mellitus type 2, and kidney stones. (wikipedia.org)
  • Those who failed either had some underlying resistance to Rilpivirine at baseline, or had low levels of Rilpivirine at 8 weeks, or had any of the two HIV subtypes (A6/A1). (theseoultimes.com)
  • In 1988 he joined the DuPont Company where he worked both as a bench scientist on HIV drug resistance then designed the clinical trials supporting FDA approval of efavirenz. (stanford.edu)
  • The potential of 3CLpro-inhibitors to select for drug-resistant variants needs to be established. (biorxiv.org)
  • To overcome this drug resistance and inhibit viral maturation, targeting Gag alongside protease rather than targeting protease alone may be more efficient. (a-star.edu.sg)
  • PrEP, which may result in HIV drug resistance. (nos-nop.org)
  • Ghosh AK, Dawson ZL, Mitsuya H. Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV. (proteopedia.org)
  • The heartening procession of new drug candidates continued with discussion of Tibotec's protease inhibitor TMC 114. (natap.org)
  • An increase of transmitted drug resistance was observed in the InfCareHIV cohort. (lu.se)
  • In 1999 he became Vice President of Regulatory Affairs at Visible Genetics Inc. and led the FDA clearance of the TRUGENE HIV-1 drug resistance test. (stanford.edu)
  • 1. Shitara Y, Sugiyama Y. Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: drug-drug interactions and interindividual differences in transporter and metabolic enzyme functions. (degruyter.com)
  • Improved access to viral load and drug resistance testing is not enough to improve viral suppression in children with HIV, researchers from Kenya and the United States reported at the Conference on Retroviruses and Opportunistic Infections (CROI 2022) this week. (aidsmap.com)
  • The hypothesis of Opt4Kids was that point-of-care viral load testing and early referral for drug resistance testing would speed up clinical decision-making resulting in improved treatment outcomes among children with HIV. (aidsmap.com)
  • Causes of viral rebound can include drug resistance, poor adherence to an HIV treatment regimen or interrupting treatment. (aidsmap.com)
  • Study participants were randomised to receive point-of-care viral load testing every three months and drug resistance testing if they had a viral load above 1000, or to receive the standard of care, which consists of viral load testing every six months and resistance testing only in the case of second-line regimen failure. (aidsmap.com)
  • The investigational HIV integrase inhibitor elvitegravir taken once daily continued to perform as well as twice-daily raltegravir ( Isentress ) at 96 weeks for treatment-experienced people with extensive drug resistance, according to data presented last week at the 19th International AIDS Conference in Washington, DC. (aidsmap.com)
  • Richard Elion from Whitman-Walker Health presented long term data from a head-to-head phase III randomised controlled trial comparing 150mg elvitegravir once daily or 400mg raltegravir twice daily, both in combination with a fully active boosted protease inhibitor plus a third drug. (aidsmap.com)
  • The purpose of this survey was to estimate the prevalence of viral load (VL) suppression and emergence of HIV drug resistance (HIVDR) among individuals receiving antiretroviral therapy (ART) for 36 months or longer in Viet Nam using a nationally representative sampling method. (who.int)
  • 1 The HIV epidemic of viral load (VL) suppression and HIV drug resistance in Viet Nam remains concentrated primarily (HIVDR) patterns at the national scale were unknown. (who.int)
  • According to HIV sentinel surveillance, the HIV a national y representative estimate of VL suppression prevalence was 11.0% in PWID, 2.7% in FSW and and acquired HIV drug resistance (ADR). (who.int)
  • Inhibitors of the proteasome, such as bortezomib are now front-line drugs for the treatment of multiple myeloma. (wikipedia.org)
  • The SARS-CoV-2 main protease (3CLpro) has an indispensable role in the viral life cycle and is a therapeutic target for the treatment of COVID-19. (biorxiv.org)
  • Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus. (aidsmap.com)
  • 5 Furthermore, these behaviors can lead to regimen discontinuation, development of ART resistance, disease progression, and increased mortality risk. (psychiatrist.com)
  • Ideally, agents used in a HAART regimen should have a robust genetic barrier to resistance. (ajmc.com)
  • HIV-1 protease) and blocking proteolytic cleavage of protein precursors that are necessary for the production of infectious viral particles. (wikipedia.org)
  • resistance protein 1 (hMDR1). (fabretp.org)
  • The major components in the cell that maintain proteostasis are the intracellular proteases which interact with the protein synthesis machinery. (soci.org)
  • Attachment inhibitors bind to a specific protein on the outer surface of HIV. (medlineplus.gov)
  • Genotypic and phenotypic methods are commonly used for detecting antiviral resistance in clinical HIV-1 and HCV specimens. (biomedcentral.com)
  • Although the etiology is unknown, angiolipomas have been shown to be associated with systemic disease, such as diabetes mellitus and HIV, and a link to HIV protease inhibitors has also been documented in several case reports. (jcadonline.com)