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12 Diseases |  |
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- | Vemlidy (tenofovir alafenamide) / Gilead
Preclinical, Journal: Adipocyte differentiation of 3T3-L1 cells under TAF, TDF and INSTIs selective challenge: an in vitro model. (Pubmed Central) - Feb 27, 2023
Our data support the evidence that in-vitro challenge of 3T3-L1 cells with INSTIs is able to increase adipocytic differentiation and to drive a number of these cells toward the expression of fibroblastic features, with a different degree according to the various drugs used whereas TAF and TDF have an antagonistic role on this phenomenon.
- Improvement of endothelial glycocalyx thickness in treatment na (C / 05) - Feb 4, 2023 - Abstract #ECCMID2023ECCMID_3852;
- HIV reservoir evaluation in GALT and PBMCs of virologically suppressed patients (Arena 3) - Feb 4, 2023 - Abstract #ECCMID2023ECCMID_1663;
- | Journal: Drug-drug interactions of Integrase Strand Transfer Inhibitors among older people living with HIV: Interazioni farmacologiche degli inibitori delle integrase tra le persone anziane che vivono con HIV. (Pubmed Central) - Jan 31, 2023
Despite the shared mechanism of action, INSTIs differ in pharmacokinetics, contributing to different drug-drug interactions. This review summarized the potential drug interactions of INSTIs and the management of the drug interactions in clinical practice.
- | Journal: Cystatin C in addition to creatinine for better assessment of glomerular renal function decline in people with HIV receiving antiretroviral therapy. (Pubmed Central) - Jan 26, 2023
This study highlighted significant differences in eGFR depending on the renal marker used in PWH, having a significant impact on CKD classification. eGFRcys should be an additive tool for patients having eGFRcreat around 60 ml/min per 1.73 m2 for better identification of renal impairment.
- | Journal: Primary resistance to integrase inhibitors in Shenzhen. (Pubmed Central) - Jan 1, 2023
Continued surveillance for resistance to INSTIs is recommended and treatment regimens should be adopted based on the pattern of resistance to INSTIs. Dolutegravir or bictegravir is first recommended when considering INSTIs as treatment regimens.
- | Journal: Transmitted drug resistance to integrase based first-line HIV antiretroviral regimens in the Mediterranean Europe. (Pubmed Central) - Dec 27, 2022
We present the most recent data on TDR to integrase based first-line regimens in Europe. Given the low prevalence of CRR to second generation integrase inhibitors and to first-line NRTIs, in the years 2018-2021 it is unlikely that newly diagnosed PWH in MeditRes countries would present with baseline resistance to a first-line regimen based on second generation integrase inhibitors.
- || Review, Journal: Different Pathways Conferring Integrase Strand-Transfer Inhibitors Resistance. (Pubmed Central) - Dec 24, 2022
To counteract these resistant mutants, second-generation INSTI drugs have been developed: Dolutegravir (DTG), Cabotegravir (CAB), and Bictegravir (BIC)...The role of unintegrated viral DNA is also discussed as a new pathway involved in conferring resistance to INSTIs. This allows us to have a more detailed understanding of HIV resistance to these inhibitors, which may contribute to the development of new INSTIs in the future.
- | Vemlidy (tenofovir alafenamide) / Gilead, Vitekta (elvitegravir) / Japan Tobacco, Gilead
Journal: Single dose topical inserts containing tenofovir alafenamide fumarate and elvitegravir provide pre- and post-exposure protection against vaginal SHIV infection in macaques. (Pubmed Central) - Nov 25, 2022
Inserts containing TAF/EVG provided high protection against vaginal SHIV infection when administered within a 4 h window before or after SHIV exposure. Our results support the clinical development of TAF/EVG inserts for on-demand PrEP and PEP in women.
- || Review, Journal: Integrase strand transfer inhibitors use in children with perinatal HIV-1 infection: a narrative review. (Pubmed Central) - Nov 16, 2022
Our results support the clinical development of TAF/EVG inserts for on-demand PrEP and PEP in women. The evidence supports high efficacy and low toxicity of INSTIs in pediatric and adolescent populations and their role as preferred ART regimens as recommended by the WHO and US guidelines recommendations.
- | Triumeq (dolutegravir/abacavir/lamivudine) / ViiV Healthcare, Descovy (emtricitabine/tenofovir alafenamide) / Gilead, Vitekta (elvitegravir) / Japan Tobacco, Gilead
Retrospective data, Journal: Weight changes after first-line antiretroviral initiation in a cohort of HIV-positive patients in Southern Spain (CAPOTA study). (Pubmed Central) - Nov 15, 2022
After ART initiation patients gain weight regardless of the regimen they take. Weight gain is associated with AIDS and the use of TAF/FTC/EVG/c.
- || Vemlidy (tenofovir alafenamide) / Gilead, Vitekta (elvitegravir) / Japan Tobacco, Gilead
PK/PD data, Journal: Pharmacokinetics and efficacy of topical inserts containing tenofovir alafenamide fumarate and elvitegravir administered rectally in macaques. (Pubmed Central) - Nov 8, 2022
Adding a second insert led to an increase in TFV and EVG in rectal tissues resulting in higher (>90%) efficacy. These results highlight the high efficacy of TAF/EVG inserts as topical on-demand rectal PrEP, as well as the need for appropriate drug coverage in the deep rectum and colon to achieve high protection.
- || Review, Journal: Interactions of Antiretroviral Drugs with Food, Beverages, Dietary Supplements, and Alcohol: A Systematic Review and Meta-analyses. (Pubmed Central) - Nov 2, 2022
Didanosine, zalcitabine, zidovudine, efavirenz, amprenavir, fosamprenavir, and indinavir should be taken on an empty stomach for maximum patient benefit...There is insufficient evidence available to make recommendations about consuming juice or alcohol with antiretroviral drugs. Resolving drug-food interactions may contribute to maximized cART effectiveness and safety.
- || Review, Journal: A clinical review of HIV integrase strand transfer inhibitors (INSTIs) for the prevention and treatment of HIV-1 infection. (Pubmed Central) - Oct 30, 2022
There are currently four approved for use in treatment-naïve individuals living with HIV; these include first generation raltegravir, elvitegravir, and second generation dolutegravir and bictegravir...Few INSTI resistance-associated mutations have been reported in clinical trials involving dolutegravir, bictegravir and cabotegravir...This review summarizes key clinical considerations of INSTIs in terms of clinical pharmacology, drug-drug interactions, resistance, and provides perspective on clinical decision-making. Additionally, we summarize major clinical trials evaluating the efficacy and safety of INSTIs in treatment-naïve patients living with HIV as well as individuals at risk of acquiring HIV infection.
- | lomibuvir (VX 222) / Trek Therapeutics, Vitekta (elvitegravir) / Japan Tobacco, Gilead
FDA event, Preclinical, Journal: A Transcriptomics-Based Bioinformatics Approach for Identification and In Vitro Screening of FDA-Approved Drugs for Repurposing against Dengue Virus-2. (Pubmed Central) - Oct 28, 2022
Results revealed that five compounds, viz., resveratrol, doxorubicin, lomibuvir, elvitegravir, and enalaprilat, have significant anti-DENV activity. Further, molecular docking studies showed that these drugs can interact with a variety of protein targets of DENV, including the glycoprotein, the NS5 RdRp, NS2B-NS3 protease, and NS5 methyltransferase The in vitro and in silico results, therefore, reveal that these drugs have the ability to decrease DENV-2 production, suggesting that these drugs or their derivatives could be attempted as therapeutic agents against DENV infections.
- | Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) / Gilead
Journal: EVG/COBI/FTC/TAF BIOEQUIVALENCE COMPARING WHOLE TABLETS TO TABLETS DISSOLVED IN TAP WATER. (Pubmed Central) - Oct 28, 2022
These changes were judged to be clinically insignificant. Dissolving EVG/COBI/FTC/TAF in water may be suitable for those with pill swallowing challenges.
- | Journal: Excessive weight gain: current antiretroviral agents in virologically suppressed people with HIV. (Pubmed Central) - Oct 21, 2022
Virologically suppressed, antiretroviral therapy (ART)-experienced PWH switching to TAF/FTC with darunavir/cobicistat (DRV/c), elvitegravir/cobicistat (EVG/c), dolutegravir (DTG), or bictegravir (BIC) were selected...In conclusion, in this study of virologically suppressed, ART-experienced PWH switching to regimens containing TAF/FTC and either DRV/c, EVG/c, DTG or BIC, up to 18% experienced excessive levels of weight gain. However, no statistically significant difference was observed across regimens.
- | Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD), Vitekta (elvitegravir) / Japan Tobacco, Gilead
Retrospective data, Journal: Integrase inhibitors in children and adolescents: clinical use and resistance. (Pubmed Central) - Oct 5, 2022
INI-based regimens were effective and safe for HIV treatment in children and adolescents. Dolutegravir and elvitegravir presented an excellent profile, and most patients achieved and maintained viral suppression.
- | Journal: Prevalence of resistance mutations associated with integrase inhibitors in therapy-naive HIV-positive patients in Baoding, Hebei province, China. (Pubmed Central) - Oct 4, 2022
All INSTI-resistant strains were cross-resistant. The primary INSTI drug resistance rate among newly diagnosed HIV-infected patients in Baoding was low, but monitoring and research on HIV INSTI resistance should be strengthened in Baoding because INSTI-based regimen prescriptions are anticipated to increase in the near future.
- Initial plasma HIV-1 RNA and CD4+ T-cell count are determinants of virological outcomes with initial integrase inhibitor-based regimens: a prospective multinational RESPOND cohort consortium () - Oct 4, 2022 - Abstract #HIVGlasgow2022HIV_Glasgow_352;
Low baseline CD4+ T-cell counts are associated with higher VF rates. This association remains even in the context of INSTIs including dolutegravir-based regimens.
- bictegravir (GS-9883) / Gilead, Descovy (emtricitabine/tenofovir alafenamide) / Gilead
Liver enzyme variation after switching to emtricitabine/tenofovir alafenamide/bictegravir is associated with glucose increase in a real-life cohort () - Oct 4, 2022 - Abstract #HIVGlasgow2022HIV_Glasgow_287;
In experienced PLWHIV, switching to FTC/TAF/BIC is associated with a significant amelioration of lipid profile, but with an increase of ALT and glucose. The correlation between ALT and glucose increase suggests a potential role of insulin resistance in the development of ALT increase.
- Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) / Gilead
Switch to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people living with HIV aged 65 years or older: W24 results of the BICOLDER study - IMEA 057 () - Oct 4, 2022 - Abstract #HIVGlasgow2022HIV_Glasgow_166;
P4
Materials and The BICOLDER study (NCT04222283) is a multicentric, prospective, single-arm study conducted in virologically controlled PLWHIV aged 65 years or older (PLWHIV 65+) who switched from a booster antiretroviral containing regimen, ritonavir or cobicistat, to B/F/TAF...At screening, 75% of the participants were receiving elvitegravir/cobicistat, and 25% a boosted PI-containing regimen... These results suggest that B/F/TAF is safe, effective in this elderly HIV population with a long history of HIV infection, multiple comorbidities and comedication.
- | Vemlidy (tenofovir alafenamide) / Gilead
Journal: Weight gain and metabolic effects in persons with HIV who switch to ART regimens containing integrase inhibitors or tenofovir alafenamide. (Pubmed Central) - Sep 24, 2022
Among VS persons who switched ART, INSTI and TAF use were independently associated with BMI increases. During eight months post-switch, BMI changes were greatest and most associated with INSTI use; afterward, gradual BMI gain was largely TAF-associated.
- | Descovy (emtricitabine/tenofovir alafenamide) / Gilead, Isentress (raltegravir) / Merck (MSD), Vitekta (elvitegravir) / Japan Tobacco, Gilead
Journal, Real-world evidence: Real-World Medication Persistence among HIV-1 Patients Initiating Integrase Inhibitor-Based Antiretroviral Therapy in Japan. (Pubmed Central) - Sep 14, 2022
During eight months post-switch, BMI changes were greatest and most associated with INSTI use; afterward, gradual BMI gain was largely TAF-associated. Among PLWH newly prescribed an INSTI-based regimen in Japan, STRs were associated with longer persistence than MTRs.
- | Descovy (emtricitabine/tenofovir alafenamide) / Gilead, Vitekta (elvitegravir) / Japan Tobacco, Gilead
Journal: Use of Tenofovir Alafenamide/Emtricitabine/Elvitegravir-Cobicistat in HIV-Naive Patients with Advanced Disease: GENIS Study. (Pubmed Central) - Sep 13, 2022
Among PLWH newly prescribed an INSTI-based regimen in Japan, STRs were associated with longer persistence than MTRs. the use of TAF/FTC/EVG-c in patients with advanced HIV disease in our study demonstrated efficacy comparable to data from pivotal clinical trials with a good safety profile.
- | Tivicay (dolutegravir) / ViiV Healthcare
Journal: Dolutegravir in Pregnancy as Compared with Current HIV Regimens in the United States. (Pubmed Central) - Sep 10, 2022
No clear differences in adverse birth outcomes were observed with dolutegravir-based ART as compared with non-dolutegravir-based ART, although samples were small. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).
- HIV reservoir evaluation in GALT and PBMCs of virologically suppressed patients (Hall BC - Arena 3) - Sep 8, 2022 - Abstract #IDWeek2022IDWEEK_2426;
- HIV-1 Drug Resistance in Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Rhode Island, USA (Hall B + C) - Sep 8, 2022 - Abstract #IDWeek2022IDWEEK_1821;
- Tivicay (dolutegravir) / ViiV Healthcare
Effectiveness and Durability of Dolutegravir (DTG)-Based Regimens in Older People Living with HIV (PLWH) from the Veterans Aging Cohort Study (VACS) (Hall B + C) - Sep 8, 2022 - Abstract #IDWeek2022IDWEEK_1815;
- HIV reservoir evaluation in GALT and PBMCs of virologically suppressed patients (Hall B + C) - Sep 8, 2022 - Abstract #IDWeek2022IDWEEK_1778;
- | Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD), Vitekta (elvitegravir) / Japan Tobacco, Gilead
Journal: Changes in Body Mass Index after Initiation of Antiretroviral Treatment: Differences by Class of Core Drug. (Pubmed Central) - Sep 3, 2022
INSTIs are associated with faster weight gain. INSTIs' increased risk of treatment emergent obesity and, possibly, weight-related co-morbidities should be judged against their improved efficacy and tolerability but increased clinical attention is required.
- | Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD), Vitekta (elvitegravir) / Japan Tobacco, Gilead
Journal: Integrase Strand Transfer Inhibitor (INSTI) Genotypic Resistance Analysis in Treatment-nNaive, INSTI Free Antiretroviral-Experienced and INSTI-Experienced Turkish Patients Infected with HIV-1. (Pubmed Central) - Aug 24, 2022
In viral rebound under INSTI treatment, INSTI-resistant mutations follow typical INSTI resistance pathways and high resistance rates. INSTI resistance genotypic analysis should be considered before any DTG-based regimes can be initiated in the future, and reduced DTG susceptibility should be carefully monitored and investigated.
- ||| Vitekta (elvitegravir) / Japan Tobacco, Gilead
Clinical: I know of at least one RCT using elvitegravir. Any clinical trials coming to Vandy? (Twitter) - Jul 26, 2022
- || Review, Journal: Approved HIV reverse transcriptase inhibitors in the past decade. (Pubmed Central) - Jul 20, 2022
Novel RT inhibitors such as islatravir, MK-8504, MK-8507, MK8583, IQP-0528, and MIV-150 will be also highlighted. Future development may focus on the new generation of novel antiretroviral inhibitors with higher bioavailability, longer elimination half-life, more favorable side-effect profiles, fewer drug-drug interactions, and higher activities against circulating drug-resistant strains.
- | Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD), Vitekta (elvitegravir) / Japan Tobacco, Gilead
Journal: Effectiveness of integrase strand transfer inhibitors in HIV-infected treatment-experienced individuals across Europe. (Pubmed Central) - Jul 15, 2022
Both VF and INSTI discontinuation occur at substantial rates in viraemic subjects. Detection of DRMs in a proportion of INSTI-experienced individuals makes INSTI resistance testing mandatory after failure.
- | Vitekta (elvitegravir) / Japan Tobacco, Gilead
Journal: Anti-HIV drug elvitegravir suppresses cancer metastasis via increased proteasomal degradation of m6A methyltransferase METTL3. (Pubmed Central) - Jul 9, 2022
Elvitegravir, originally developed to treat human immunodeficiency virus (HIV) infection, suppressed metastasis by directly targeting METTL3 and enhancing its STUB1-mediated proteasomal degradation. Overall, RNA m6A modifications are important in cancer metastasis, and targeting METTL3 with elvitegravir has therapeutic potential for treating ESCC.
- | Vitekta (elvitegravir) / Japan Tobacco, Gilead
Journal: Incidence of low-level viremia and its impact on virologic failure among people living with HIV-1 who switched to elvitegravir-based antiretroviral therapy. (Pubmed Central) - Jun 22, 2022
Overall, RNA m6A modifications are important in cancer metastasis, and targeting METTL3 with elvitegravir has therapeutic potential for treating ESCC. The risks of LLV and VF were low in PLWH who had achieved virologic suppression and switched to EVG/c/FTC/TAF, and the presence of LLV and prior exposure to raltegravir increased the risk of VF.
- || Retrospective data, Review, Journal: Evidence synthesis evaluating body weight gain among people treating HIV with antiretroviral therapy - a systematic literature review and network meta-analysis. (Pubmed Central) - Jun 22, 2022
For backbones, TAF led to higher weight gain relative to tenofovir disoproxil fumarate (TDF), abacavir, and zidovudine...Further research is needed to better understand long-term outcomes and their relationship to other metabolic outcomes. The WHO Global HIV, Hepatitis and Sexually Transmitted Infections Programmes.
- | Observational data, Retrospective data, Journal: Retrospective evaluation of an observational cohort by the Central and Eastern Europe Network Group shows a high frequency of potential drug-drug interactions among HIV-positive patients receiving treatment for coronavirus disease 2019 (COVID-19). (Pubmed Central) - Jun 11, 2022
Although low-dose steroids are mainly used for COVID-19 treatment, comedication with boosted antiretrovirals seems to have the most frequent potential for DDIs. In addition, attention should be paid to NNRTI coadministration.
- | Journal: Associations of modern initial antiretroviral drug regimens with all-cause mortality in adults with HIV in Europe and North America: a cohort study. (Pubmed Central) - Jun 8, 2022
This large study of patients starting ART since the introduction of INSTIs found little evidence that mortality rates differed between most first-line ART regimens; however, raltegravir-based regimens were associated with higher mortality. Although unmeasured confounding cannot be excluded as an explanation for our findings, virological benefits of first-line INSTIs-based ART might not translate to differences in mortality.
- || Review, Journal: Comprehensive Review on Different Analytical Techniques for HIV 1- Integrase Inhibitors: Raltegravir, Dolutegravir, Elvitegravir and Bictegravir. (Pubmed Central) - May 29, 2022
Although, antiretroviral drugs are extensively used but data suggests that limited studies have been conducted for determination of impurity profile and stability. This therefore, presents a scope to detect and validate impurities in order to meet ICH guidelines for their limits and further to improve the quality and safety of antiretroviral drugs.
- Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD), Vitekta (elvitegravir) / Japan Tobacco, Gilead
Effects of integrase strand transfer inhibitors (INSTIs) on body mass index and blood pressure in children living with HIV () - May 12, 2022 - Abstract #AIDS2022AIDS_816;
Dolutegravir, raltegravir and elvitegravir were prescribed for 33 (29%), 43 (38%), and 37 (33%), respectively. INSTI-containing regimens do not appear to be associated with increases in BMI percentile or BP in CLWPH in Canada.
- Dovato (dolutegravir/lamivudine) / ViiV Healthcare, Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) / Gilead
Switching to Dolutegravir/lamivudine or Bictegravir/Emtricitabine/Tenofovir alafenamide. A comparative real-world study () - May 12, 2022 - Abstract #AIDS2022AIDS_765;
Both treatments were effective and well-tolerated in the real-world setting. The few discontinuations in the B/T/F group seem related to the switch from TDF.
- Dovato (dolutegravir/lamivudine) / ViiV Healthcare
Integrase resistance emergence with dolutegravir/lamivudinewith prior HIV-1 suppression () - May 12, 2022 - Abstract #AIDS2022AIDS_762;
ART with DRV/c/FTC/TAF + DTG 50 mg BID was started in October 2020. This is the first reported case of integrase resistance selection in an INI-naive individual treated with co-formulated DTG/3TC started as a switch strategy following a prior long-term virological suppression.
- Advanced HIV infection in the US: immune response to ART initiation () - May 12, 2022 - Abstract #AIDS2022AIDS_745;
In the OPERA cohort, all ART-naïve, adults with advanced HIV (CD4200 cells/µL). No difference was observed in CD4:CD8 ratio changes over time across groups; CD4:CD8 ratio normalization was rare with all regimens.
- Vitekta (elvitegravir) / Japan Tobacco, Gilead
Multi-medicine use and potential drug'drug interactions among people living with HIV on antiretroviral therapy in Australia () - May 12, 2022 - Abstract #AIDS2022AIDS_731;
Patterns of interactions vary by cART regimen and occur even among people on novel single-tablet regimens. Selecting regimens based on patient's comorbidities and comedications is key to optimising treatment.
- Incidence of cardiometabolic outcomes among people living with HIV initiated on INSTI versus non-INSTI antiretroviral therapies () - May 12, 2022 - Abstract #AIDS2022AIDS_700;
Among treatment-naïve PWH in the US, INSTI initiation was associated with greater risk of developing congestive heart failure, myocardial infarction, and lipid disorders during a short follow-up period. With increasing life expectancy among PWH, further research including additional clinical variables and using longer follow-up is warranted to examine the impact of INSTI-containing ART on long-term clinical outcomes.
- | Isentress (raltegravir) / Merck (MSD), Vitekta (elvitegravir) / Japan Tobacco, Gilead
Journal: Integrase Strand Transfer Inhibitors are Associated with Incident Diabetes Mellitus in People with HIV. (Pubmed Central) - May 7, 2022
With increasing life expectancy among PWH, further research including additional clinical variables and using longer follow-up is warranted to examine the impact of INSTI-containing ART on long-term clinical outcomes. INSTI use was associated with increased risk of new-onset diabetes mellitus/hyperglycemia in the six months following ART initiation.
- | Edurant (rilpivirine) / J&J, Tivicay (dolutegravir) / ViiV Healthcare, Vitekta (elvitegravir) / Japan Tobacco, Gilead
Journal: Reduction of CD8 T cell functionality but not inhibitory capacity by integrase inhibitors. (Pubmed Central) - Apr 29, 2022
In summary, our study provides first evidence on a significant, negative impact on CD8 T cell effector functions in the presence of two INSTIs, dolutegravir and elvitegravir, which may contribute to the limited success of eradicating HIV-infected cells through "shock-and-kill" strategies. Although our findings are coherent with recent studies highlighting a possible role of dolutegravir in weight gain, further investigations are necessary to fully understand the impact of INSTI-based regimens on the health of the individual during antiretroviral therapy.
- | bictegravir (GS-9883) / Gilead
Journal: First report of computational protein-ligand docking to evaluate susceptibility to HIV integrase inhibitors in HIV-infected Iranian patients. (Pubmed Central) - Apr 5, 2022
Several analyses were performed including docking screening, genotypic resistance, secondary/tertiary structures, post-translational modification (PTM), immune epitopes, etc. The average docking energy (E value) of different samples with elvitegravir (EVG) and raltegravir (RAL) was more than other INTIs...Some conserved motifs and specific amino acids in INT-protein binding sites have characterized that mutation(s) in them may disrupt INT-drugs interaction and cause a significant loss in susceptibility to INTIs. Good adherence, treatment of naïve patients, and monitoring injection drug users are fundamental factors to control HIV infection in Iran effectively.