- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD), Vitekta (elvitegravir) / Japan Tobacco, Gilead
[VIRTUAL] WEIGHT GAIN AMONG PWH WHO SWITCH TO ART-CONTAINING InSTIs OR TAF () - Mar 18, 2021 - Abstract #CROI2021CROI_714;
During the first 8 months post-switch, the rate of weight gain was greatest and mostly associated with InSTI use; after that, continued gradual weight gain was mostly associated with TAF use. These data help define the individual contribution, magnitude, and duration of effect upon weight gain of InSTI and TAF use.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD), Vitekta (elvitegravir) / Japan Tobacco, Gilead
[VIRTUAL] ASSOCIATION BETWEEN INTEGRASE INHIBITORS (InSTIs) AND CARDIOVASCULAR DISEASE (CVD) () - Mar 18, 2021 - Abstract #CROI2021CROI_698;
In the large RESPOND collaboration use of InSTIs was associated with an increased incidence of CVD in the first 6 months of exposure after accounting for known CVD risk factors including the ART backbone and across a wide range of sensitivity analyses. While we cannot fully exclude possible channeling bias or residual confounding, these findings call for further investigations.
- |||||||||| bictegravir (GS-9883) / Gilead
[VIRTUAL] EVALUATION OF COMBINATIONS OF CLINICAL INTEGRASE MUTATIONS ON InSTI RESISTANCE () - Mar 18, 2021 - Abstract #CROI2021CROI_641;
Chimeric viruses were grown in a reporter CD4+ T-cell line in the presence of 0.01-1,000nM raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), cabotegravir (CAB), and bictegravir (BIC), where infection was measured by imaging cytometry. High-level resistance to DTG, CAB and BIC requires multiple integrase substitutions including compensatory mutations.
- |||||||||| [VIRTUAL] MUTATIONS IN GP41 IN PRIMARY HIV-1 ISOLATES CONFER RESISTANCE TO ANTIRETROVIRALS () - Mar 18, 2021 - Abstract #CROI2021CROI_633;
We propagated clinically relevant HIV-1 strains [subtype B NL(AD8) and subtype C, transmitted founder K3016] in the presence of DTG, rilpivirine and emtricitabine to select variants exhibiting resistance to these drugs...These Env mutants exhibit faster-than-WT replication but reduced cell-free infectivity relative to WT and showed reduced sensitivity to DTG (3.6 – 30 fold), efavirenz (9.5 – 23 fold) and nelfinavir (13 – 25 fold), but not to T-20, in spreading infection... Our findings suggest that Env-mediated drug resistance may broadly affect HIV sensitivity to ARVs and provide clues towards understanding how ART failure occurs without mutations in drug-target genes.
- |||||||||| Isentress (raltegravir) / Merck (MSD)
[VIRTUAL] W96 EFFICACY OF 4/7 DAYS MAINTENANCE ART STRATEGY: ANRS-170 QUATUOR TRIAL () - Mar 18, 2021 - Abstract #CROI2021CROI_628;
P3
The efficacy result of 4/7-days strategy was sustained at W96, with a low rate of viral failure, particularly with InSTI based regimen. This 4 consecutive days-on and 3 days-off reduced the cost ART maintenance regimens and represents a real, workable, alternative to the recommended maintenance therapy
- |||||||||| Isentress (raltegravir) / Merck (MSD), Istodax (romidepsin) / Astellas, BMS
[VIRTUAL] NANOPARTICLE-DCs RESTORE CYTOTOXIC MEMORY-LIKE NK CELLS IN CHRONIC HIV PATIENTS () - Mar 18, 2021 - Abstract #CROI2021CROI_463;
Finally, NK cells from treated HIV patients were incubated with autologous CD4+ T cells in the presence of IL-2, Raltegravir and Romidepsin. Conditioning of DC with PI:C-nanoparticles is a promising tool to restore natural cytotoxic function of CD16+ NK cells from chronic ART-treated HIV-1 patients and more efficiently targeting HIV-1 infected CD4+ T cells.
- |||||||||| Isentress (raltegravir) / Merck (MSD), VRC01 / Acuitas Therap
[VIRTUAL] MULTIPLY INFECTED ACH2 CELLS ARE RESPONSIBLE FOR THE MAJORITY OF ACH2 HIV PRODUCTION () - Mar 18, 2021 - Abstract #CROI2021CROI_387;
These data show that even low pass ACH2 contain a significant number of HIV-superinfected cells. These cells produce far more multiply spliced HIV RNA and far higher amounts of virus than cells which contain only 1 proviral copy and are responsible for the majority of HIV produced by bulk ACH2 cells.
- |||||||||| Isentress (raltegravir) / Merck (MSD)
[VIRTUAL] “An Intruder Is Causing a Hollow in My Lung”: A Rare Case of Necrotizing Pneumonia in an Immunocompromised Patient () - Mar 14, 2021 - Abstract #ATS2021ATS_636;
We present the case of a 39-year-old woman with medical history of HIV diagnosed since 2012 on emtricitabine/tenofovir and raltegravir who presented to the urgency department due to non-productive cough of 3 days of evolution...aeruginosa is associated with high mortality and poor prognosis in immunocompromised patients and septic shock. The aim of this case is to raise awareness of pseudomonas necrotizing pneumonia for early detection, adequate management and better outcomes.
- |||||||||| Isentress (raltegravir) / Merck (MSD)
Trial completion date, Trial primary completion date: Pharmacokinetics Distribution of Raltegravir by PET/MR (clinicaltrials.gov) - Mar 12, 2021
P1, N=10, Recruiting,
This work suggests that Q-GRFT and ARV co-administration in free or encapsulated forms may improve efficacy in achieving prophylaxis. Trial completion date: Jan 2021 --> Jan 2022 | Trial primary completion date: Nov 2020 --> Nov 2021
- |||||||||| bictegravir (GS-9883) / Gilead
Journal: Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes. (Pubmed Central) - Mar 3, 2021
BIC also had a longer t and maintained longer antiviral activity after drug washout than DTG with the clinically relevant resistance IN mutant G140S+Q148H. Structural analyses indicate that BIC makes more contacts with the IN-DNA complex than DTG mainly via its bicyclic ring system which may contribute to more prolonged residence time and resilience against many resistance mutations.
- |||||||||| Isentress (raltegravir) / Merck (MSD)
Journal: Switch from tenofovir DF to raltegravir is not associated with weight gain over 96 weeks. (Pubmed Central) - Feb 20, 2021
In 37 virologically suppressed adults (36 men, mean age 49 years) who switched from tenofovir disoproxil fumarate to raltegravir 400 mg twice daily, mean weight changes from baseline at Weeks 24, 48 and 96 were not significant (maximum 0.8 kg at Week 24; all p≥0.16). Weight gain may not occur with all INSTIs.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD), Vitekta (elvitegravir) / Japan Tobacco, Gilead
Clinical, Journal: Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors. (Pubmed Central) - Feb 11, 2021
Our findings confirmed that in INSTI-naïve patients, major INSTI-RMs occur very rarely. Under INSTI treatment, selection of drug-resistance follows the typical drug-resistance pathways; a higher evolution characterizes integrase sequences developing drug-resistance compared to those without any resistance.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Journal: Biochemical activity of RAGs is impeded by Dolutegravir, an HIV integrase inhibitor. (Pubmed Central) - Feb 11, 2021
Binding and nicking studies showed that, Dolutegravir could decrease the binding efficiency of RAG1 domains and cleavage on DNA substrates, but not as considerably as Elvitegravir. Thus, we show that although the integrase inhibitors such as Elvitegravir show an affinity towards RAG1, the newer molecules may have lesser side-effects.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD), Vitekta (elvitegravir) / Japan Tobacco, Gilead
Clinical, Journal: Starting or Switching to an Integrase Inhibitor-Based Regimen Affects PTSD Symptoms in Women with HIV. (Pubmed Central) - Feb 5, 2021
DTG-based regimens either did not affect, or worsened symptoms, in both naïve and switch patients. Further studies are needed to determine mechanisms underlying differential effects of EVG, RAL and DTG on stress symptoms in WWH.
- |||||||||| ritonavir / Generic mfg.
[VIRTUAL] Iatrogenic Cushing Syndrome and Secondary Adrenal Insufficiency Due to an Interaction Between Fluticasone and Ritonavir. (On-Demand) - Feb 2, 2021 - Abstract #ENDO2021ENDO_744;
A treatment with fluticasone 1 inh / 24h, salbutamol on demand, darunavir 800 mg / day and ritonavir 100 mg / day.He had known lipodystrophy since 2001 and the abdominal perimeter was controlled, showing an increase in it...It was restarted, antibiotic treatment was prescribed, and she was discharged home with a new regimen of antiretrovirals (raltegravir, tenofovir, and abacavir)...For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO 2021.
- |||||||||| Trial completion date, Trial termination: RESIST-2: 2nd-line ART for HIV-2 Infection (clinicaltrials.gov) - Jan 25, 2021
P=N/A, N=152, Terminated,
We found no clear evidence of an overall increase in rate of weight gain following switch to INSTI in virologically-suppressed individuals. Trial completion date: Jul 2022 --> May 2020 | Active, not recruiting --> Terminated; COVID-19 and Funding
- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare
Clinical, Journal, Adverse events: Analysis of Pharmacovigilance Databases for Dolutegravir Safety in Pregnancy. (Pubmed Central) - Jan 8, 2021
Given widespread use of new antiretroviral drugs worldwide and anticipated use of new drugs, prospective follow-up of pregnant women and birth surveillance studies such as Tsepamo are critically needed.Neural tube defects have been reported among infants born from women taking a wide range of antiretrovirals in 4 pharmacovigilance databases. Safety reports were inconsistent between databases and very hard to interpret.
- |||||||||| Isentress (raltegravir) / Merck (MSD)
Journal: Telomere and ATM dynamics in CD4 T cell depletion in active and virus-suppressed HIV infection. (Pubmed Central) - Jan 5, 2021
Specifically, we established an in vitro HIV T-cell culture system with viral replication and raltegravir (RAL; an integrase inhibitor) suppression, mimicking active and ART-controlled HIV infection in vivo We demonstrated that HIV-induced, telomeric DDR plays a pivotal role in triggering telomere erosion, premature T-cell aging, and CD4 T-cell apoptosis or depletion via dysregulation of the PI3K/ATM pathways...We demonstrated that HIV-induced telomeric DDR plays a critical role in inducing telomere loss, premature cell aging, and CD4 T cell apoptosis or depletion via dysregulation of the PI3K/ATM pathways. This study sheds new light on the molecular mechanisms of telomeric DDR and its role in CD4 T cell homeostasis during HIV infection.
- |||||||||| Januvia (sitagliptin) / Merck (MSD)
Journal: Exploiting cheminformatic and machine learning to navigate the available chemical space of potential small molecule inhibitors of SARS-CoV-2. (Pubmed Central) - Jan 5, 2021
Fragment-based scaffold analysis and R-group decomposition uncovered pyrrolidine and the indole molecular scaffolds as the potent fragments for designing and synthesizing the novel drug-like molecules for targeting SARS-CoV-2. This comprehensive and systematic assessment of small-molecule viral therapeutics' entire chemical space realised critical insights to potentially privileged scaffolds that could aid in enrichment and rapid discovery of efficacious antiviral drugs for COVID-19.
- |||||||||| bictegravir (GS-9883) / Gilead
Review, Journal, Adverse events: Update on Adverse Effects of HIV Integrase Inhibitors. (Pubmed Central) - Jan 3, 2021
This is worrying since patients from African descent are at higher risk of cardio-vascular events and increased body mass index (BMI) can cause further increase metabolic risk. There is possibly an additional effect of tenofovir alafenamide (TAF) on weight increase.Discrepancies between clinical trials - with low rates of adverse events - and reports from real-life settings might be due partly to under-representation of some groups of patients in clinical trials, and/or the short duration of follow-up, since some adverse effects may only occur after prolonged exposure.Preliminary data on safety of bictegravir (BIC), from clinical trials and non-trial settings, are very reassuring and seem to show lower rates of adverse events compared to DTG.Elvitegravir/cobicistat (EVG/cobi) need to be used with caution in patients with other co-morbidities given potential for polypharmacy, as it is the case for aging patients, because of the high potential of drug-drug interactions due to effects of the cobicistat booster.We are awaiting the release of cabotegravir (CAB), which could represent a good option for patients struggling with adherence, despite injection site reactions.Pharmacogenetics is a promising way to explore adverse effects occurrence in the INSTI class.
- |||||||||| Isentress (raltegravir) / Merck (MSD)
Review, Journal: Therapeutic potential of oxadiazole or furadiazole containing compounds. (Pubmed Central) - Jan 1, 2021
There are different examples of commercially available drugs which consist of 1,3,4-oxadiazole ring such as nitrofuran derivative (Furamizole) which has strong antibacterial activity, Raltegravir as an antiviral drug and Nesapidil drug is used in anti-arrhythmic therapy. This present review summarized some pharmacological activities and various kinds of synthetic routes for 2, 5-disubstituted 1,3,4-oxadiazole, and their derived products.
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