- |||||||||| [VIRTUAL] Sonidegib in a patient with multiple basal cell carcinoma and HIV infection (ePoster Terminal 1) - Sep 20, 2020 - Abstract #ADO2020ADO_126;
So far, there is only one case report of the use of Sonic hedgehog inhibitors in combination with antiretroviral therapy for HIV infection in which vismodegib was administered in combination with emtricitabine, rilpivirine and tenofovir [1]. Our case shows for the first time an impressive therapeutic success with sonidegib in comedication with ritonavir, daltegravir and darunavir.
- |||||||||| Journal: Virological Failure and Acquired Genotypic Resistance Associated With Contemporary Antiretroviral Treatment Regimens. (Pubmed Central) - Sep 10, 2020
Six companion drugs were used in 93.3% of regimens: efavirenz, elvitegravir/c, dolutegravir, b-darunavir, rilpivirine, and raltegravir...In multivariable analyses, younger age, lower CD4 count, higher virus load, and b-atazanavir were associated with increased VF risk; lower CD4 count, higher virus load, and nevirapine were associated with increased HIVDR risk...Despite the frequent use of contemporary ART regimens, VF and HIVDR continue to occur. Further efforts are required to improve long-term ART virological responses to prevent the consequences of ongoing HIV-1 replication including virus transmission and HIVDR.
- |||||||||| Edurant (rilpivirine) / J&J, Rekambys (rilpivirine LA) / J&J
[VIRTUAL] Antiviral Activity and Safety of Long-acting Cabotegravir (CAB LA) Plus Long-acting Rilpivirine (RPV LA), Administered Every 2 Months (Q2M), in Hiv-positive Subjects: Results from the POLAR Study (On Demand) - Sep 10, 2020 - Abstract #IDWeek2020IDWEEK_2535;
LATTE participants who completed 312 weeks on study, with plasma HIV-1RNA< 50c/mL at screening, were eligible for POLAR and offered the option to switch to CAB LA+RPV LA Q2M or to the oral fixed dose combination of dolutegravir (DTG)/rilpivirine (RPV) once daily, for continued maintenance of HIV-1RNA suppression. CAB LA+RPV LA, administered Q2M, resulted in durable virologic suppression, an acceptable tolerability profile, and high levels of participant satisfaction over the first 12 mo of treatment in POLAR.
- |||||||||| Preclinical, Journal: Anti-HIV and anti-HCV drugs inhibit p-glycoprotein efflux activity in Caco-2 cells and precision-cut rat and human intestinal slices. (Pubmed Central) - Aug 20, 2020
Lopinavir, ritonavir, saquinavir, atazanavir, maraviroc, ledipasvir, and daclatasvir inhibited the efflux of a model ABCB1 substrate, rhodamine 123 (RHD123), in Caco-2 cells and rat-derived PCIS...Abacavir, zidovudine, tenofovir disoproxil fumarate, etravirine, and rilpivirine did not inhibit intestinal ABCB1...Our data help clarify the molecular mechanisms responsible for reported increases in the bioavailability of ABCB1 substrates including antivirals and drugs prescribed to treat co-morbidity. These results could help guide the selection of combination pharmacotherapies and/or suitable dosing schemes for patients infected with HIV and/or HCV.
- |||||||||| bictegravir (GS-9883) / Gilead
[VIRTUAL] Weight Gain Associated With Antiretroviral Therapy () - Aug 14, 2020 - Abstract #IDWeek2020IDWEEK_2249;
As PWH are living longer on effective ARV therapy, monitoring for weight gain is required as obesity contributes to morbidity and mortality from cardiovascular disease and metabolic diseases. Key factors for weight gain in our clinic population include male gender, baseline diagnosis of hypertension, use of TAF, bictegravir use, and rilpivirine use.
- |||||||||| Pifeltro (doravirine) / Merck (MSD), Tivicay (dolutegravir) / ViiV Healthcare
[VIRTUAL] Dolutegravir and Doravirine in Combination: When Standard Antiretroviral Regimens are Unacceptable () - Aug 14, 2020 - Abstract #IDWeek2020IDWEEK_1223;
Doravirine is attractive for this population as it can be used in renal impairment, moderate hepatic impairment, is unaffected by timing of meals, and (unlike rilpivirine) has no interaction with proton pump inhibitors. Dolutegravir is included in NRTI-sparing regimens that HHS guidelines suggest should be considered in older PWH, especially with CKD.
- |||||||||| Edurant (rilpivirine) / J&J
Clinical, Journal: Concentration-response model of rilpivirine in a cohort of HIV-1-infected naive and pre-treated patients. (Pubmed Central) - Aug 12, 2020
The concentration-response relationship of rilpivirine was satisfactorily described for the first time using an original population pharmacodynamic model. Simulations performed using the final model showed that the currently used 50 ng/mL rilpivirine trough plasma concentration efficacy target might need revision upwards, particularly in pre-treated patients.
- |||||||||| Edurant (rilpivirine) / J&J
Journal: Sex and Gender Differences in Rilpivirine based ART - Data from the HIVCENTER Frankfurt. (Pubmed Central) - Aug 2, 2020
While virologic overall response rates to rilpivirine based ART were high for both treatment-experienced and -naïve patients the proportion of discontinuations was significantly higher in women (24.2% vs. 11.7%; p = 0.024; ODDS-Ratio = 2.41; CI 1.12 - 5.18). Although the total number of patients with virologic failure was low (4.1%), the higher rate of ART discontinuations in female patients receiving RPV require close monitoring in the first months of treatment addressing special needs of women living with HIV.
- |||||||||| Prezista (darunavir) / J&J, Tivicay (dolutegravir) / ViiV Healthcare
Clinical, Journal, Real-World Evidence: Real-World Experience with Dolutegravir-Based Two-Drug Regimens. (Pubmed Central) - Jul 30, 2020
Prior to commercial availability of the single-tablet 2DRs, DTG 2DR components were primarily used in treatment-experienced patients for treatment simplification and avoidance of long-term toxicities. Many of these patients achieved and maintained virologic suppression, with low discontinuation rates.
- |||||||||| Edurant (rilpivirine) / J&J, Prezcobix (darunavir/cobicistat) / Gilead, J&J, Tivicay (dolutegravir) / ViiV Healthcare
Trial completion date, Trial primary completion date: Effect on HIV Medications on EPC Cells (clinicaltrials.gov) - Jul 23, 2020
P=N/A, N=30, Recruiting,
Many of these patients achieved and maintained virologic suppression, with low discontinuation rates. Trial completion date: Sep 2020 --> Dec 2020 | Trial primary completion date: Jun 2020 --> Oct 2020
- |||||||||| Pifeltro (doravirine) / Merck (MSD)
Review, Journal: Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty years. (Pubmed Central) - Jul 10, 2020
In this paper, we review the development of NNRTIs in the last two decades using the above optimization strategies, including their structure-activity relationships, molecular modeling, and their binding modes with HIV-1 reverse transcriptase (RT). Future directions and perspectives on the design and associated challenges are also discussed.
- |||||||||| Prezista (darunavir) / J&J, Tivicay (dolutegravir) / ViiV Healthcare
Journal: Trends in HIV-1 Drug Resistance Mutations from a U.S. Reference Laboratory from 2006 to 2017. (Pubmed Central) - Jul 9, 2020
Sequences with ≥1 darunavir DRM declined from 18.1% to 4.8% by 2017...Prevalence of elvitegravir-associated DRMs T66A/I/K, E92Q, S147G, and the dolutegravir-associated DRM R263K increased...These trends may inform the need for baseline genotypic resistance testing. The detection of treatment-emergent DRMs in serially-tested patients confirms the value of genotypic testing following virologic failure.
- |||||||||| Edurant (rilpivirine) / J&J
Journal: Suppression of Zika Virus Infection in the Brain by the Antiretroviral Drug Rilpivirine. (Pubmed Central) - Jun 28, 2020
Histopathological examination of the brains from infected animals revealed that RPV reduced ZIKV RNA levels in the hippocampus, frontal cortex, thalamus, and cerebellum. Repurposing of NNRTIs, such as RPV, for the inhibition of ZIKV replication offers a possible therapeutic strategy for the prevention and treatment of ZIKV-associated disease.
- |||||||||| emtricitabine/tenofovir disoproxil fumarate / Generic mfg., Tivicay (dolutegravir) / ViiV Healthcare, abacavir/lamivudine / Generic mfg.
Journal: Factors Associated With Weight Gain in People Treated With Dolutegravir. (Pubmed Central) - Jun 28, 2020
At 6 and 12 months, weight gain was highest among PWH on TDF/FTC+DTG and TAF/FTC+DTG...Higher weight (HR, 0.97 by 1 kg; 95% CI, 0.96 to 0.99) and female gender (HR, 0.54; 95% CI, 0.33 to 0.88) were protective against weight gain. Naïve PWH with lower CD4 counts and those on TAF/FTC or TDF/FTC backbones were at higher risk of weight increase in the course of DTG-based ART.
- |||||||||| [VIRTUAL] Neutrophilic eccrine hidradenitis as a result of nucleoside reverse transcriptase Inhibitor () - Jun 20, 2020 - Abstract #AADVMX2020AAD-VMX_196;
NEH is a rare neutrophilic dermatosis that primarily occurs in patients with acute myeloid leukemia undergoing chemotherapy, most commonly with cytarabine.(1,2) Rarely, it has been reported as a paraneoplastic phenomenon.(2) Additionally, there are few reported cases of NEH in patients with HIV receiving nucleoside reverse transcriptase inhibitors (NRTI) and one case of a patient with HIV receiving both integrase and protease inhibitors.(3-5) NEH has also been reported in one patient with HIV not receiving antiretroviral therapy.(6) In our patient, evaluation for underlying malignancy was negative, however, a medication review revealed that he was treated with a combination antiretroviral agent of rilpivirine, tenofovir, and the NRTI emtricitabine for at least one year prior to onset of NEH, which we attribute as the cause of his NEH. Thus, while the pathogenesis of NEH remains unclear, it is important for clinicians to consider this neutrophilic dermatosis in HIV patients treated with NRTIs.
- |||||||||| bictegravir (GS-9883) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare
Review, Journal: Non-Nucleoside Reverse Transcriptase Inhibitors Join Forces with Integrase Inhibitors to Combat HIV. (Pubmed Central) - Jun 19, 2020
In the treatment of acquired immune deficiency syndrome (AIDS), the diarylpyrimidine (DAPY) analogs etravirine (ETR) and rilpivirine (RPV) have been widely effective against human immunodeficiency virus (HIV) variants that are resistant to other non-nucleoside reverse transcriptase inhibitors (NNRTIs)...In a separate development, HIV integrase strand transfer inhibitors (INSTIs) have shown efficacy in treating AIDS, including raltegravir (RAL), elvitegravir (EVG), cabotegravir (CAB), bictegravir (BIC), and dolutegravir (DTG)...Here, highly resistant emergent mutations and efficacy data on these novel treatments are reviewed. Overall, ETR or RPV, in combination with INSTIs, may be treatments of choice as long-term maintenance therapies that optimize efficacy, adherence, and safety.
- |||||||||| cabotegravir (GSK1265744) / ViiV Healthcare, Edurant (rilpivirine) / J&J
Clinical, Journal: Antiretroviral adherence for adolescents growing up with HIV: understanding real life, drug delivery and forgiveness. (Pubmed Central) - Jun 13, 2020
Pragmatically, such regimens tolerate the intermittent adherence so characteristic of adolescence, preserving immune function, without the rapid evolution of resistance. The potential role of long-acting injectable ART, specifically cabotegravir and rilpivirine, is discussed and future strategies including ultra-long-acting drug-delivery systems and broadly neutralising monoclonal antibodies explored.
- |||||||||| Edurant (rilpivirine) / J&J
Clinical, P3 data, Journal: Efficacy and safety of dolutegravir-rilpivirine for maintenance of virological suppression in adults with HIV-1: 100-week data from the randomised, open-label, phase 3 SWORD-1 and SWORD-2 studies. (Pubmed Central) - Jun 12, 2020
P3
The potential role of long-acting injectable ART, specifically cabotegravir and rilpivirine, is discussed and future strategies including ultra-long-acting drug-delivery systems and broadly neutralising monoclonal antibodies explored. The combination of dolutegravir plus rilpivirine sustained virological suppression of HIV-1, was associated with a low frequency of virological failure, and had a favourable safety profile, which support its use as a nucleoside reverse transcriptase inhibitor-sparing and protease inhibitor-sparing alternative to three-drug regimens that reduces overall exposure to ART.
- |||||||||| efavirenz / Merck (MSD), Generic mfg., Edurant (rilpivirine) / J&J, nevirapine / Generic mfg.
Biomarker, Journal: NNRTI Hyper-Susceptibility and Resistance: Mutational Analysis of Residue 181 in HIV-1 Reverse Transcriptase. (Pubmed Central) - Jun 10, 2020
Furthermore, inhibitor-bound Y181F RT-T/P was less efficient than the WT complex in incorporating the next correct dNTP, and this could be attributed to increased mobility of Y181F RT on the T/P substrate. Collectively, our data highlight the key role that Y181 in RT plays in NNRTI binding.
- |||||||||| Edurant (rilpivirine) / J&J
Biomarker, Clinical, Journal, Tumor Mutational Burden: Impact of the mutational load on the virological response to a first-line rilpivirine-based regimen. (Pubmed Central) - Jun 8, 2020
There is quantifiable evidence that determining a mutational load threshold can be used to identify those patients on a first-line regimen containing rilpivirine who are at risk of virological failure. The clinical management of HIV-infected patients can be improved by evaluating the frequency of mutant variants at a threshold of < 20% together with the plasma HIV-1 viral load at the time of resistance genotyping.
- |||||||||| Tivicay (dolutegravir) / ViiV Healthcare
Clinical, Journal: Lung Transplant in HIV-Infected Patients. Single Centre Experience. (Pubmed Central) - May 30, 2020
The clinical management of HIV-infected patients can be improved by evaluating the frequency of mutant variants at a threshold of < 20% together with the plasma HIV-1 viral load at the time of resistance genotyping. The experience of the first five VIH LT patients in Spain shows that LT is feasible without increasing the risk of infectious or immunological complications.
- |||||||||| Edurant (rilpivirine) / J&J, Cabenuva (cabotegravir long acting/rilpivirine long acting) / J&J, GSK, ViiV Healthcare, Pfizer, Shionogi
Enrollment closed: More Options for Children and Adolescents (MOCHA): Oral and Long-Acting Injectable Cabotegravir and Rilpivirine in HIV-Infected Children and Adolescents (clinicaltrials.gov) - May 27, 2020
P1/2, N=155, Active, not recruiting,
These results are very reassuring for doravirine use in naive patients. Recruiting --> Active, not recruiting
- |||||||||| Pifeltro (doravirine) / Merck (MSD)
Journal: The journey of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) from lab to clinic. (Pubmed Central) - May 9, 2020
In this perspective, we focus on the six NNRTIs and lessons learned from their journey through development to clinical studies. It demonstrates the obligatory need of understanding the physicochemical and biological principles (lead optimization), resistance mutations, synthesis and clinical requirements for drugs.
- |||||||||| Edurant (rilpivirine) / J&J, lamivudine / Generic mfg., Odefsey (emtricitabine/rilpivirine/tenofovir alafenamide) / Gilead, J&J
Journal: Evaluating emtricitabine + rilpivirine + tenofovir alafenamide in combination for the treatment of HIV-infection. (Pubmed Central) - May 6, 2020
Finally, adverse effects and drug-drug interaction data with FTC/RPV/TAF are discussed.Expert opinion: TAF/FTC/RPV can be used as an initial regimen for people living with HIV whose HIV RNA 200 cells/mm when INSTI-based regimens are not a treatment option. Future antiretroviral therapy development may focus on dual therapy-based regimens containing RPV, particularly as long-acting formulations.
- |||||||||| Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate) / Gilead, BMS, Merck (MSD)
Clinical, Journal: Lipidomics Reveals Reduced Inflammatory Lipid Species and Storage Lipids after Switching from EFV/FTC/TDF to RPV/FTC/TDF: A Randomized Open-Label Trial. (Pubmed Central) - Apr 30, 2020
Patients ≥ 18 years old on EFV co-formulated with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) with HIV-RNA < 50 copies/mL for ≥6 months were randomized to continue EFV/FTC/TDF (n = 14) or switch to RPV/FTC/TDF (n =15)...Patients on RPV/FTC/TDF showed a decrease in the global amount of storage lipids (-0.137 log [fold-change] EFV vs. 0.059 log [fold-change] RPV) but an increase in lysophosphatidylcholines (LPCs) and total steroids. Compared with EFV, RPV increased metabolites with anti-inflammatory properties and reduced the repository of specific lipotoxic lipids.
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