Intelence (etravirine) / J&J - LARVOL DELTA

AI-driven discovery of antiretroviral drug bictegravir and etravirine as inhibitors against monkeypox and related poxviruses. (PubMed, Commun Biol) - "These findings support the repurposing of bictegravir and etravirine for treating mpox, especially for patients co-infected with HIV, warranting follow-up clinical investigation. The established AI pipeline and our antiviral drug discovery strategies bear major implications for responding to the ongoing mpox emergency and preparing for future poxvirus epidemics."

Journal • Human Immunodeficiency Virus • Infectious Disease

Switching from etravirine to doravirine in virologically suppressed people with HIV: results from the French multicentre SWEED observational study. (PubMed, J Antimicrob Chemother) - "Doravirine-based ART maintained virological suppression in PWH switching from etravirine-based ART, even in presence of prior NNRTI resistance. Its once-daily dosing, favourable safety profile, and minimal drug interactions support its use in long-term ART strategies."

Journal • Observational data • Human Immunodeficiency Virus • Infectious Disease • CD4

Potential treatment options following virological failure with long-acting injectable cabotegravir and rilpivirine: an analysis based on reported cases (EACS 2025) - "Purpose : Virological failure (VF) with long-acting injectable cabotegravir and rilpivirine (LAI-CAB/RPV) is rare but may lead to selection of resistance-associated mutations (RAMs) that limit future treatment options. Resistance to CAB/RPV was common, being more prevalent among people with A compared to non-A subtypes. Reduced susceptibility to alternative treatment options was more pronounced for INI (dolutegravir/bictegravir) than for NNRTI (doravirine/etravirine)."

Clinical • Human Immunodeficiency Virus • Infectious Disease

IMPACT OF PREEXISTING K103N ON THE EFFECTIVINES OF LA-CAB+RPV: REAL-LIFE RELATIVITY COHORT (EACS 2025) - "Purpose : K103N is a nonpolymorphic NNRTI resistance-associated mutation (RAM) selected in people with HIV (PWH) treated with nevirapine (NVP) or efavirenz (EFV). It reduces susceptibility to NVP and EFV by approximately 50-fold and 20-fold, respectively, but does not affect susceptibility to rilpivirine (RPV), etravirine (ETR), or doravirine (DOR)...BASELINE CHARACTERISTICS REGARDING THE PRESENCE OF K103N Conclusions : The presence of the K103N mutation was not associated with an increased risk of virological failure in PWH treated with LA-CAB+RPV. These findings suggest that a history of K103N should not preclude the use of this regimen."

Clinical • Human Immunodeficiency Virus • Infectious Disease

Exploring Potential for Repurposing Antiretroviral Drugs Etravirine and Efavirenz in Prostate and Bladder Cancer. (PubMed, Pharmaceuticals (Basel)) - " EFV and ETV exhibit selective anticancer activity in prostate and bladder cancer cells, with enhanced effects when combined. These findings support their potential as repurposed therapeutic agents and warrant further preclinical evaluation for prostate and bladder cancer therapy."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Bioisosterism-driven design of orally active, safe, and broad-spectrum biphenyl-DAPY derivatives as highly potent HIV-1 non-nucleoside reverse transcriptase inhibitors. (PubMed, Acta Pharm Sin B) - "Furthermore, this analog exhibited minimal adverse effects with significantly reduced cytotoxicity (CC50 = 195 μmol/L) and a high selectivity index (SI = 102,608), superior to those of etravirine (CC50 > 4.6 μmol/L, SI > 1436) and rilpivirine (CC50 = 3.98 μmol/L, SI = 3989). Additionally, A12 exhibited favorable oral bioavailability (F = 29.2%) and an extended elimination half-life (T 1/2 = 13.56 h), enabling convenient oral administration at minimal doses. These findings indicated that A12 could serve as a promising drug candidate for HIV treatment."

Journal • Human Immunodeficiency Virus • Infectious Disease

Network controllability analysis reveals the antiviral potential of Etravirine against hepatitis E virus infection. (PubMed, mSystems) - "Etravirine is a Food and Drug Administration-approved non-nucleoside reverse transcriptase inhibitor, used for the treatment of AIDS patients. This study reveals the potential of repurposing Etravirine for the treatment of HEV patients and illustrates the importance of computational biology in antiviral drug discovery."

Journal • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Liver Failure • PRKCB

Prevalence of HIV drug resistance, its correlates and common mutations among people living with HIV failing on ART in northern Uganda: A cross-sectional study. (PubMed, PLoS One) - "The study found a high HIVDR prevalence strongly associated with long ART duration which is likely to lead to increased ART treatment failure rates. The high Etravirine resistance and increasing Dolutegravir resistance are likely to complicate future treatment options while low Darunavir resistance makes it a future third-line treatment option. Strengthening routine resistance surveillance, timely VL monitoring, and adherence support are critical to mitigating drug resistance and preserving ART effectiveness among PLHIV in the West-Nile region."

Journal • Observational data • Retrospective data • Human Immunodeficiency Virus • Infectious Disease

Simultaneous Quantification of Doravirine, Lamivudine, and Tenofovir Disoproxil Fumarate in Human Plasma by UPLC-MS/MS: Method Development and Validation. (PubMed, Turk J Pharm Sci) - "A novel, high-throughput liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique has been developed that uses Etravirine (ETR) as the internal standard (IS) to simultaneously quantify Doravirine (DOR), Lamivudine (LAM), and Tenofovir Disoproxil Fumarate (TDF) in human plasma. The developed bioanalytical method, validated in accordance with ICH M10 guidelines, demonstrated high accuracy, precision, and reproducibility for the simultaneous quantification of DOR, LAM, and TDF. Its streamlined design and reliable performance make it a valuable tool for routine analysis."

Journal

Synthesis and biological evaluation of N-acyl diaryl pyrimidines (NDAPYs) as novel reverse transcriptase inhibitors. (PubMed, Bioorg Med Chem) - "In this study, we designed novel molecules by the addition of a N-acyl group to the C4-position of Rilpivirine/Etravirine basic scaffold, a well-known class of DAPYs, in order to provide more interactions with K103 and E138 in Reverse Transcriptase. This was leading, as expected, to better in vitro RT inhibition, and the compounds 12c (56 %) and 12 k (49 %) demonstrated three-fold higher potency than Doravirine (17 %)...However, the absence of correlation with cytotoxicity advocates an alternative mode of action that ought to be determined. Altogether, these studies indicate that the C4-position of diaryl pyrimidines could be important and warrants further investigated towards optimization of potential reverse transcriptase inhibitors."

Journal • Human Immunodeficiency Virus • Infectious Disease • Oncology

Screening of the FDA-approved drug library identifies CCL17 inhibitors that block arthritic pain. (PubMed, Sci Rep) - "In this study, we screened a panel of 1508 FDA-approved drugs and identified five drugs, namely fluoxetine, ractopamine, ponesimod, terbutaline and etravirine, which potently inhibited CCL17 production without adverse effects on cell viability and CCL22 formation in human monocytes and mouse macrophages. Significantly, therapeutic administration of these five drugs in an inflammatory arthritis model revealed that fluoxetine, ractopamine, ponesimod and terbutaline could inhibit arthritic pain, correlating with decreased CCL17 expression. Given the need for new and safe anti-inflammatory therapeutics to treat RA and the benefits of repurposing existing drugs for new indications, our findings reported here offer four new promising analgesics for treating inflammatory pain."

FDA event • IO biomarker • Journal • Preclinical • Immunology • Inflammation • Inflammatory Arthritis • Pain • Rheumatoid Arthritis • Rheumatology • CCL2 • CCL22 • CCR4 • CSF2 • IRF4 • STAT5 • STAT5AWqe

High level HIV drug resistance to second-generation non-nucleoside reverse transcriptase inhibitors: implications for long acting and third-line antiretroviral therapy in Tanzania (IAS-HIV 2025) - "BACKGROUND: Nevirapine and Efavirenz, first-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs served as the default first-line antiretroviral therapy (ART) for people living with HIV (PLHIV) in Tanzania between 2004 and 2018...Multivariable logistic regression identified factors associated with NNRTI-RAMs. Overall NNRTI resistance occurred in 31.9% (432/634) of study participants, with 70.1% having at least one RAM conferring resistance to both etravirine (ETR) and rilpivirine (RPV)... High-level resistance to second-generation NNRTIs suggest a compromise of their effectiveness in third-line ART regimens. The presence of RPV RAMs highlights careful selection when considering long-acting cabotegravir-rilpivirine therapy for PLHIV particularly those with adherence challenges to daily oral regimens. Notably, HIV disease stage II may be associated with an increased risk for developing RAMs, warranting further investigation."

Human Immunodeficiency Virus • Infectious Disease

Drug resistance mutations among people living with HIV and ART failure in Bangladesh: a cross-sectional study. (PubMed, Lancet Reg Health Southeast Asia) - "Seven participants showed resistance against Efavirenz, the common drug received from ART centres, and three of them were additionally resistant against Tenofovir Disoproxil Fumarate. Other drugs supplied by ART centres were also found resistant for participants; i.e. 6 against Emtricitabine, 6 against Lamivudine, and 1 against Etravirine...This study also advocates for exploring barriers to ART adherence and implementing personalized ART strategies in national ART programs. The Global Fund."

Journal • Observational data • Human Immunodeficiency Virus • Infectious Disease

HIV drug resistance, early treatment outcomes and impact of guidelines compliance after protease inhibitor-based second-line failure in a dedicated resistance clinic in western Kenya: a retrospective cohort study. (PubMed, J Int AIDS Soc) - "We found high levels of drug resistance and early VF following PI-based second-line failure in Kenya. Treatment guidelines compliance and switches to third-line, even within guidelines recommendations, improved early viral outcomes. Findings highlight the vulnerability of PLWH with advanced ART experience and resistance profiles, and the importance of following guidelines and improving access to third-line and drug resistance testing, particularly in the new ART era."

Compliance • Journal • Retrospective data • Human Immunodeficiency Virus • Infectious Disease

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors. (PubMed, J Vis Exp) - "The significant improvement suggests that the modified Etravirine holds promising potential as a novel agent in antiretroviral therapy. The obtained lower RMSD value, the enhanced amino acid interactions, and the highest binding free energy indicate that enumerated Etravirine could serve as a viable alternative for HIV/AIDS treatment."

Journal • Human Immunodeficiency Virus • Infectious Disease

HIV-1 cross-resistance to second-generation non-nucleoside reverse transcriptase inhibitors among individuals failing antiretroviral therapy in Cameroon: implications for the use of long-acting treatment regimens in low- and middle-income countries. (PubMed, JAC Antimicrob Resist) - "HIV-1 Sanger sequencing was performed on plasma and resistance-associated mutations (RAMs) to etravirine, rilpivirine and doravirine were interpreted using HIVdb program v.9.5.0 (HIVdb penalty scores were,  ≥60, high resistance; 15-59, intermediate resistance and  <15, susceptible) and the IAS-USA 2022 list. Among patients failing treatment in Cameroon, there is a high-level of cross-resistance to 2ndGenNNRTI due to wide exposure to 1stGenNNRTI. Thus, in LMICs sharing similar programmatic features, the use of NNRTI-sparing regimens should be prioritized as a public health approach, while second-generation-NNRTI long-acting regimens should be guided by genotyping or for clients without previous exposure to NNRTIs."

Journal • Human Immunodeficiency Virus • Infectious Disease

Molecular characterization and drug resistance pattern in pol gene of HIV-1 sub-subtypes circulating in Lahore, Pakistan. (PubMed, Virus Genes) - "Furthermore, the isolate QAU-AZ2 (OR086936) proposes variable degree of resistance to nevirapine (NVP), etravirine (ETR), rilpivirine (RPV), efavirenz (EFV), Doravirine (DOR); while no resistance against NNTRI and NTRI was observed in the remaining isolates. Further studies are required to (i) examine the function of identified amino acid substitutions through molecular docking, and (ii) sequence the complete pol gene of the viral isolates from Pakistani patients to determine possible drug resistance associated with amino acid substitutions."

Journal • Human Immunodeficiency Virus • Infectious Disease

Outcomes for Persons With Triple-Class Resistant HIV and a History of Virologic Failure (CROI 2025) - "Background The ANRS 139 TRIO trial provided evidence for the safety and efficacy of an antiretroviral therapy (ART) regimen containing raltegravir (RAL), etravirine (ETR), and darunavir/ritonavir (DRV/r) (combination called TRIO) for heavily treatment-experienced (HTE) people with HIV (PWH) with multidrug-resistance. Conclusions The most common outcome after starting TRIO was to switch to another ≥3 drug regimen. These patients had few options to switch to less burdensome regimens."

Human Immunodeficiency Virus • Infectious Disease

Drug resistance mutations to integrase inhibitors, proteinase, and reverse transcriptase inhibitors in newly diagnosed HIV-1 infections in Hebei province, China, 2018-2022. (PubMed, Front Cell Infect Microbiol) - "In the PR-RT gene coding region, E138EK/G was the most common (1.6%), followed by K103N (1.4%), G190GE/A/S (0.6%), K101E (0.5%), A98G (0.4%), and T215I/TS (0.3%), associated with the low- to high-level resistance to doravirine (DOR), efavirenz (EFV), etravirine (ETR), nevirapine (NVP), rilpivirine (RPV), and zidovudine (AZT)...G163GRS/EK, P145PS, Y143S, and T66A were associated with the resistance to elvitegravir (EVG) and raltegravir (RAL). S153SF and Q148QH were mainly related to the resistance to dolutegravir (DTG), bictegravir (BIC), and caboteravir (CAB)...The overall prevalence of HIV-1 PDR in Hebei is high, belonging to a moderate resistant level (5.0%-15.0%). It is necessary for us to strengthen the effective surveillance of PDR among treatment-naive patients, and we should adjust the treatment plan according to the results of PDR surveillance."

Journal • Human Immunodeficiency Virus • Infectious Disease

Discovery of Potential Anthelmintic Agents Against Gyrodactylus kobayashii Through Computer-Aided Drug Design and In Vivo Evaluation. (PubMed, J Fish Dis) - "Subsequent in vivo anthelmintic efficacy and acute toxicity assays in goldfish revealed etravirine as a potent candidate with an EC50 value of 0.55 mg/L and a therapeutic index (TI) greater than 18.18. Molecular dynamics simulations confirmed stable binding modes for flubendazole and mebendazole with β-tubulin, providing mechanistic insights into their anthelmintic activity. Overall, this study demonstrated the utility of CADD in identifying potential therapeutic agents against monogenean and underscored the importance of β-tubulin as a key target for anthelmintic therapy, contributing to the development of sustainable aquaculture practices."

Journal • Preclinical • Infectious Disease

Unraveling a novel therapeutic facet of Etravirine to confront Hepatocellular Carcinoma via disruption of cell cycle. (PubMed, Sci Rep) - "This captured the binding affinity of Steviolbioside towards CDK1 and Etravirine and Fludarabine towards CDK2. In this drug repurposing venture, Etravirine, a non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV, emerged as a promising candidate for HCC treatment. The findings warrant further preclinical and clinical investigations to ascertain the repurposable potential of Etravirine against HCC, particularly in patients with viral infections."

Journal • Hepatocellular Cancer • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor • CCNA2 • CDK1

Structure-based discovery of novel diarylpyrimidines as potent and selective Non-Nucleoside reverse transcriptase inhibitors: From CH(CN)-Biphenyl-Diarylpyrimidines to CNNH2-Biphenyl-Diarylpyrimidines. (PubMed, Eur J Med Chem) - "Furthermore, this analogue exhibited approximately 11-fold lower cytotoxicity (CC50 = 54 μM) than that of etravirine and rilpivirine. No acute toxicity or organ damage was observed at a dose of 2 g/kg. Overall, M44 represents a highly promising lead compound that warrants further optimization efforts to identify potential anti-HIV-1 drug candidates."

Journal • Human Immunodeficiency Virus • Infectious Disease

Predicted environmental concentration (PEC), environmental risk assessment (ERA) and prioritization of antiretroviral drugs (ARVs) in seawater from Guarujá (Brazilian coastal zone). (PubMed, Mar Environ Res) - "Regarding the results of the mixture of ARVs, the ERA showed a high acute and/or chronic risk for all five classes tested, i.e., (i) nucleoside/nucleotide reverse transcriptase inhibitors; ii) non-nucleoside reverse transcriptase inhibitors; iii) protease inhibitors; (iv) integrase strand transfer inhibitors; and (v) chemokine receptor antagonists. Ultimately, the final ranking of the OPBT approach was etravirine (the highest-priority ARV in seawater from Guarujá), followed by: nevirapine > efavirenz > ritonavir > lopinavir > maraviroc > atazanavir > darunavir > abacavir > dolutegravir > zidovudine > tenofovir > lamivudine."

Journal • Human Immunodeficiency Virus • Infectious Disease

SWEED: Switch From Etravirine to Doravirine as a Part of Antiretroviral Combination (clinicaltrials.gov) - P=N/A | N=109 | Completed | Sponsor: Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida | Recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Sep 2024

Trial completion • Trial completion date • Human Immunodeficiency Virus • Infectious Disease

Discovery of Dual Targeting GSK-3β/HIV-1 Reverse Transcriptase Inhibitors as Neuroprotective Antiviral Agents. (PubMed, ACS Chem Neurosci) - "We show for the first time that the approved drugs, etravirine and rilpivirine, possess GSK-3β activity (IC50 619 nM and 502 nM, respectively). We have also identified 3 lead molecules exhibiting IC50 < 1 μM (11726169, 12326205, and 12326207), with compound 11726169 being the most potent in vitro GSK-3β inhibitor (IC50 = 12.1 nM). We also describe the generation of machine learning models for GSK-3β inhibition and their validation with our data as an external test set and propose their use for the future optimization of such inhibitors."

Journal • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Dementia • Developmental Disorders • Human Immunodeficiency Virus • Infectious Disease • Mood Disorders • Movement Disorders • Psychiatry • Rare Diseases