- |||||||||| raltegravir / Generic mfg.
Journal: Analysis of raltegravir analogs to enhance inhibitory efficiency against HIV integrase. (Pubmed Central) - May 14, 2025
The analysis of inhibitor potentials against the HIV-1 integrase enzyme through molecular dynamics simulation reveals that RAL5 has strong inhibitory potential for treating viral diseases. These findings contribute to the promotion of therapeutic intervention methods in this field.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, raltegravir / Generic mfg., Vitekta (elvitegravir) / Japan Tobacco, Gilead
Journal: Investigation of Integrase Inhibitor Resistance Mutations in gp41 in Clinical Samples. (Pubmed Central) - May 13, 2025
These findings contribute to the promotion of therapeutic intervention methods in this field. While off-target INSTI substitutions may arise in vivo, there is currently insufficient evidence to recommend expanding INSTI resistance testing to include Env.
- |||||||||| Clinical, Journal: Dolutegravir-based Antiretroviral Therapy in People With HIV With Solid Organ Transplantation: A Single-arm Pilot Clinical Trial (DTG-SOT). (Pubmed Central) - Apr 21, 2025
P4
People with HIV with plasma viral load <50?copies/mL during ?12 months and receiving stable raltegravir-based ART during ?6 months were switched to tenofovir disoproxil fumarate/emtricitabine or lamivudine/abacavir + DTG and followed up for 48 weeks...Pharmacokinetic parameters changed, albeit not significantly, before and after ART, for mycophenolic acid (maximum [Cmax] +63%, trough [Cmin] +53%, area under the curve [AUC] +16%; n = 7) and cyclosporine A (Cmax -64%, Cmin +14%, AUC -47%; n = 2), with smaller changes for tacrolimus (Cmax +14%, Cmin -29%, AUC -9%; n = 7)...Switching to DTG-based ART was effective in people with HIV SOT recipients. More studies are needed to evaluate DTG safety in this setting.
- |||||||||| Cabenuva (cabotegravir long acting/rilpivirine long acting) / J&J, GSK, ViiV Healthcare, Pfizer, Shionogi
PK/PD data, Journal: Physiologically-based pharmacokinetic modelling of long-acting injectable cabotegravir and rilpivirine in pregnancy. (Pubmed Central) - Apr 12, 2025
Model predictions suggest that monthly long-acting cabotegravir could maintain antiviral efficacy throughout pregnancy, but that bimonthly administration may require careful clinical evaluation. Both monthly and bimonthly long-acting rilpivirine may not adequately maintain antiviral efficacy in pregnancy.
- |||||||||| PK/PD data, Journal: Pharmacokinetic approaches to standardize antiviral exposure in cerebrospinal fluid. (Pubmed Central) - Mar 28, 2025
PK modeling successfully standardized ARV CSF concentrations to a given time point (i.e., CMAX or CTrough) to allow estimation of CSF penetration. This approach provides uniformity for the assessment of exposure, for the estimation of whether desired therapeutic drug goals are obtained in the CSF, and for further studies to investigate whether CSF exposure metrics calculated using this method are associated with measures of HIV persistence.
- |||||||||| Preclinical, Journal: In Vitro and Clinical Evaluations of UGT1A1-, P-gp-, OATP1B1-, and BCRP-Mediated Drug-Drug Interactions of Belumosudil, a Potent ROCK2 Inhibitor. (Pubmed Central) - Mar 27, 2025
P1
Cmax and AUC0-last for rosuvastatin calcium increased by 3.6-fold and 4.6-fold, respectively, suggesting a clinically relevant interaction with drugs that are substrates of OATP1B1 or BCRP. There was no impact of coadministration with raltegravir, dabigatran etexilate, or rosuvastatin calcium on belumosudil pharmacokinetics, and belumosudil was well tolerated.
- |||||||||| Journal: Major role of dolutegravir in the emergence of the S147G integrase resistance mutation. (Pubmed Central) - Mar 4, 2025
In this French study, S147G emerged principally in patients on dolutegravir regimens, in association with up to five other INSTI resistance mutations. This accumulation of mutations suggests a replicative advantage on HIV strains under dolutegravir selection pressure, suggesting that caution is required when interpreting dolutegravir resistance in the presence of such S147G resistance patterns, even in patients prescribed dolutegravir twice daily.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD)
Factors Associated With Virologic Suppression in People Living With HIV and Tuberculosis in Brazil (Poster Hall) - Mar 3, 2025 - Abstract #CROI2025CROI_1412;
Conclusions In this analysis from the Brazilian national HIV/TB program, we found that initiating dolutegravir-based regimen was associated with virologic suppression 1 year after ART initiation in PWH treated for TB. Markers of HIV advanced disease and social vulnerability were negatively associated with ART effectiveness, which emphasizes the need to offer person-centred interventions to most vulnerable populations.
- |||||||||| Incident Diabetes Among People With HIV After Switching to Integrase Strand Transfer Inhibitors (Poster Hall) - Mar 3, 2025 - Abstract #CROI2025CROI_1369;
Conclusions Switching from an NNRTI or PI to an INSTI was associated with an increased risk of incident DM in this diverse cohort of PWH from multiple sites across North America. These findings inform antiretroviral prescribing and tailored risk-benefit approach for PWH, especially those with clinical concern for new-onset DM.
- |||||||||| Edurant (rilpivirine) / J&J, Isentress (raltegravir) / Merck (MSD)
Molecular Epidemiology of HIV-1 Transmitted Drug Resistance Among Subtypes Circulating in Italy (Poster Hall) - Mar 3, 2025 - Abstract #CROI2025CROI_914;
However, the impact of the detected TDR on the susceptibility to currently recommended first-line regimens is negligible. NGS genotyping can improve the characterization of transmission networks of resistance, allowing the detection of TC harbouring minority-resistant species not detectable with Sanger.
- |||||||||| GS-1720 / Gilead
In Vitro Resistance Profile for GS-1720, a Potent Once-Weekly Oral InSTI in Clinical Development (Poster Hall) - Mar 3, 2025 - Abstract #CROI2025CROI_534;
Conclusions GS-1720 exhibits an in vitro resistance profile comparable to the best-in-class INSTI bictegravir, including high barrier to resistance and minimal cross-resistance within the INSTI class. These observations support the ongoing clinical development of GS-1720 as a novel once-weekly oral INSTI.
- |||||||||| Isentress (raltegravir) / Merck (MSD)
Longitudinal Changes in Neuronal Markers and Associations With ART Initiation and Cognitive Function (Poster Hall) - Mar 3, 2025 - Abstract #CROI2025CROI_495;
Methods Biomarker concentrations were assessed at baseline (W0) and after 96 weeks (W96) in individuals randomised to commence darunavir/r and either tenofovir-DF/emtricitabine (triple-ART, n=119) or raltegravir (dual-ART, n=119) in a previously reported cognitive sub-study of NEAT-001/ANRS143...Biomarker changes were statistically significantly associated with CD4 increase (GFAP, CXCL10, sCD14, neopterin, NfL; p<0.002) but not NPZ-score. Conclusions Improvements in biomarkers of neuronal health following 2 years of ART were associated predominantly with improvements in CD4 count and partly by randomised drug arm, but not with cognitive function changes.
- |||||||||| Isentress (raltegravir) / Merck (MSD)
Visualizing the Cell Biology of HIV Latency and Reactivation (San Francisco Ballroom A) - Mar 3, 2025 - Abstract #CROI2025CROI_204;
Strikingly, the localization of proviruses to the PNC was blocked by integrase inhibitor raltegravir, which showed that this was due to spatial genome rearrangements...HIV proviruses in latently infected memory T cells from patients also accumulated in the PNC and showed identical patterns of nuclear rearrangements after cellular reactivation. Conclusions In contrast to transformed cells where proviruses are found primarily at the nuclear periphery, in primary memory T cells, P-TEFb highly restricts HIV transcription, and the nuclear architecture undergoes rearrangements that shape the transcriptional silencing and reactivation of proviral HIV.
- |||||||||| Isentress (raltegravir) / Merck (MSD)
Journal: Outcomes following prenatal exposure to raltegravir-containing antiretroviral therapy: a multi-cohort European study. (Pubmed Central) - Feb 25, 2025
Conclusions In contrast to transformed cells where proviruses are found primarily at the nuclear periphery, in primary memory T cells, P-TEFb highly restricts HIV transcription, and the nuclear architecture undergoes rearrangements that shape the transcriptional silencing and reactivation of proviral HIV. These findings add to the evidence base around safety of raltegravir use in pregnancy, though ongoing safety monitoring is needed to rule out risk of rare outcomes.
- |||||||||| Pifeltro (doravirine) / Merck (MSD), Isentress (raltegravir) / Merck (MSD)
Trial completion date, Trial primary completion date: DORAL: HIV-1 Infected Patients, Phase II Trial, Dual Combination Doravirine/Raltegravir Open Label (clinicaltrials.gov) - Jan 10, 2025
P2, N=150, Recruiting,
Thus, our study suggests that the T218I and T218S natural polymorphisms are unlikely to undermine the effectiveness of cabotegravir as a treatment and pre-exposure prophylaxis strategy. Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025
- |||||||||| Isentress (raltegravir) / Merck (MSD)
Journal: Clearance of archived integrase strand transfer inhibitors resistance mutations in people with virologically suppressed HIV infection. (Pubmed Central) - Dec 11, 2024
Most (95%) had experienced VF on a raltegravir-containing regimen...In multivariable analysis, the duration of viral replication and the level of HIV-RNA during prior VF were significantly associated with the persistence of INSTIs-RM, with odds ratios of 1.05 per week of replication (95% CI, 1.00-1.11; P?=?0.024) and 8.26 per log10 copies/mL (95% CI, 1.46-46.59; P?=?0.017). We observed a clear trend towards the clearance of archived INSTIs-RM after a long period of virological control leading to changes in the resistance profile in cellular DNA, raising the possibility of studies assessing the recycling of INSTI classes even in the presence of a history of resistance.
- |||||||||| Isentress (raltegravir) / Merck (MSD)
Journal: Repurposing raltegravir for reducing inflammation and treating cancer: a bioinformatics analysis. (Pubmed Central) - Dec 6, 2024
However, further in silico analysis has indicated that Raltegravir demonstrates a commendable interaction with the active site amino acids and exhibits the most favorable pharmacokinetic properties compared to others. Considering the results of bioinformatics tools, it can be concluded that Raltegravir as an antiviral drug could be repurposed to prevent severe inflammatory response and tumorigenesis resulting from ADAM17 malfunction.
- |||||||||| Isentress (raltegravir) / Merck (MSD)
Journal: Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Raltegravir Potassium. (Pubmed Central) - Nov 13, 2024
Raltegravir potassium can be assigned to BCS class II or IV since this compound has low solubility and uncertain permeability. Therefore, according to the ICH M9 guideline, it is not recommended to apply BCS-based biowaiver to approval of immediate release solid dosage forms of raltegravir potassium, either for new generic versions or when moderate to major changes in composition and/or the manufacturing method of the product are made.
- |||||||||| Vocabria (cabotegravir oral) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD)
ERVK integrase-driven DNA damage leads to motor deficits (Poster Hall at the Palais de Congres Montreal; 517b/c) - Nov 7, 2024 - Abstract #ALSMND2024ALS_MND_398;
Reduced movement in ERVK IN transgenics was corrected by treatment with integrase inhibitors Raltegravir or Cabotegravir, demonstrating that ERVK IN enzyme activity is tied to motor disturbances in this model Sex-specific differences in lifespan, behaviour, and drug responsiveness were also apparent. ERVK
- |||||||||| Women living with HIV: how far to fulfil the gap? () - Oct 26, 2024 - Abstract #HIVGlasgow2024HIV_Glasgow_307;
Moreover, they were characterized by higher burden of comorbidities, in particular obesity and diabetes. That led to multiple vicious circles, enhanced by different cultural, social and economic determinants: treatment choice of 3DR versus dual regimen, difficulties in screening and management of comorbidities, lower rate of cancer screening.
- |||||||||| Antiretroviral therapy in pregnancy in England in 2019?2022: common regimens and treatment modifications () - Oct 26, 2024 - Abstract #HIVGlasgow2024HIV_Glasgow_130;
Among pregnancies conceived on ART, most common (reported in >5%) first regimens were efavirenz (EFV) + tenofovir disoproxil fumarate (TDF) + emtricitabine (FTC) (13.5% [267/1974]), rilpivirine (RPV) +TDF+FTC (11.6% [228/1974]), darunavir/ritonavir (DRV/r) +TDF+FTC (8.0% [158/1974]), dolutegravir (DTG) + lamivudine (3TC) + abacavir (ABC) (7.7% [152/1974]), and raltegravir (RAL) +TDF+FTC (6.4% [127/1974]). Where ART was initiated during pregnancy (55.7% [234/420] diagnosed antenatally), median gestational age at start was 15 weeks (IQR 12
- |||||||||| Isentress (raltegravir) / Merck (MSD)
Postnatal prophylaxis among infants born to women living with HIV in England, 2018?2022 () - Oct 26, 2024 - Abstract #HIVGlasgow2024HIV_Glasgow_128;
Although caution is required due to limitations of currently available surveillance data in determining risk strata, these data provide the first partial evidence for good clinical adherence to current policies on risk strata and PNP, as well as the possible power to monitor practice using observational data. Potential modifications to ISOSS data collection tailored to upcoming guidelines would ensure any limitations are minimized.
- |||||||||| bictegravir (GS-9883) / Gilead, Isentress (raltegravir) / Merck (MSD)
PK/PD data, Journal: Ideal Time to Conduct a Pharmacokinetic Investigation After Delivery to Fully Capture the Effect of Pregnancy on Drug Exposure. (Pubmed Central) - Oct 23, 2024
Pharmacokinetic investigations on hepatically cleared drugs should not be conducted before the fifth week after delivery to fully characterize the effect of pregnancy on drug exposure. Because physiological changes remain after delivery, early measurements can underestimate the pregnancy effect on pharmacokinetics, leading to suboptimal dosing recommendations during pregnancy.
- |||||||||| Xiannuoxin (simnotrelvir) / Simcere, Shanghai Inst. of Materia Medica, Crixivan (indinavir sulfate) / Merck (MSD), Isentress (raltegravir) / Merck (MSD)
Journal: Evaluation of inhibition effect and interaction mechanism of antiviral drugs on main protease of novel coronavirus: Molecular docking and molecular dynamics studies. (Pubmed Central) - Oct 19, 2024
The interaction mechanism between antiviral drugs and main protease was analyzed in detail by calculating the root mean square displacement (RMSD), root mean square fluctuation (RMSF) and interaction residues properties. The results showed that the six drugs with high flexibility (Remdesivir, Simnotrelvir, Sofosbuvir, Ledipasvir, Indinavir and Raltegravir) had strong binding strength with 3CLpro, and the last four antiviral drugs can be used as potential candidates for main protease inhibitors.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare, Isentress (raltegravir) / Merck (MSD)
Review, Journal: Pre- and Post-Exposure Prophylaxis for HIV in Patients Taking Anti-Seizure Medications. (Pubmed Central) - Sep 23, 2024
This narrative review aims to be a resource for all clinicians prescribing ASMs so that they can create a welcoming environment to enable successful treatment of seizures and reduce the risk of HIV infection in people at risk. In addition, we highlight knowledge gaps and areas of unmet need that can be addressed with future studies.
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