- |||||||||| Dovato (dolutegravir/lamivudine) / ViiV Healthcare
Enrollment open: DOLCE: Dolutegravir-Lamivudine for na (clinicaltrials.gov) - Sep 27, 2021 P4, N=230, Recruiting, 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir. Not yet recruiting --> Recruiting
- |||||||||| emtricitabine / Generic mfg.
Clinical, Journal: A case series of emtricitabine-induced pure red cell aplasia. (Pubmed Central) - Sep 16, 2021 This study provides strong circumstantial evidence that emtricitabine plays an important role in the pathogenesis of reversible PRCA. The mechanisms through which emtricitabine induces PRCA remain unclear and require further study.
- |||||||||| zidovudine / Generic mfg.
Journal: Nucleoside Reverse Transcriptase Inhibitor (NRTI) Interaction with Human Equilibrative Nucleoside Transporters 1 and 2. (Pubmed Central) - Sep 10, 2021 This provides a method to assess the influence of nucleoside reverse transcriptase inhibitors (NRTIs) on natively expressed transporter function. Determining substrate selectivity of the ENTs in HeLa cells can be effectively translated into the activity of these transporters in Sertoli cells that comprise the blood-testis barrier, thereby assisting targeted drug development of compounds capable of circumventing the blood-testis barrier.
- |||||||||| Prezista (darunavir) / J&J, Tivicay (dolutegravir) / ViiV Healthcare
Trial completion date, Trial primary completion date: Body Composition Sub-study of the D2EFT Trial (clinicaltrials.gov) - Sep 2, 2021 P4, N=300, Recruiting, This is most notable within the CNS where drug biodistribution may be more limited with the final goal of better understanding ARV-associated efficacy and potential toxicity. Trial completion date: Jan 2022 --> Jan 2024 | Trial primary completion date: Jan 2022 --> Jan 2023
- |||||||||| rifampicin / Generic mfg.
Journal: SARS-CoV-2 RdRp Inhibitors Selected from a Cell-Based SARS-CoV-2 RdRp Activity Assay System. (Pubmed Central) - Aug 28, 2021 Moreover, the Z-factor of this system was calculated to be 0.798, suggesting the reproducibility and reliability of the high-throughput screening system. Finally, we screened nucleoside and nucleotide analogs and identified adefovir dipivoxil, emtricitabine, telbivudine, entecavir hydrate, moroxydine and rifampin as novel SARS-CoV-2 RdRp inhibitors and therapeutic candidates for COVID-19 This system provides an effective high-throughput screening system platform for developing potential prophylactic and therapeutic drugs for COVID-19 and emerging coronavirus infections.
- |||||||||| Tybost (cobicistat) / Gilead, Tivicay (dolutegravir) / ViiV Healthcare, Vemlidy (tenofovir alafenamide) / Gilead
Clinical, Journal: Residual viremia in HIV-infected patients who continue a 2-drug or switch to a 3-drug integrase strand transfer inhibitor-based regimen. (Pubmed Central) - Aug 8, 2021 In this randomized, single-center, open-label, 96-week, superiority, controlled trial of 50 HIV-infected patients with HIV-RNA <50 copies/mL on a two-drug regimen based on dolutegravir plus one reverse transcriptase inhibitor, switching to a single tablet regimen of cobicistat, elvitregravir, emtricitabine plus tenofovir alafenamide did not appear to mitigate the burden of residual viremia, both at week 48 and at week 96. The immunological changes observed during follow-up and the safety of the two regimens were similar.
- |||||||||| emtricitabine / Generic mfg.
Journal: Application of a Scavenger Receptor A1 Targeted Polymeric Prodrug Platform for Lymphatic Drug Delivery in HIV. (Pubmed Central) - Aug 4, 2021 As a proof-of-concept, the HIV antiviral emtricitabine (FTC) was conjugated to the polymer's succinyl groups via ester bonds, with a drug loading of 14.2% (wt/wt)...In a pharmacokinetic study in rats, the prodrug achieved ~7 to 19-fold higher concentrations in lymphatic tissues compared to FTC control, supporting lymphatic-targeted drug delivery. We believe the SR-A1-targeted macromolecular PLS prodrug platform has extraordinary potential for treatment of infectious diseases.
- |||||||||| emtricitabine / Generic mfg.
Journal: Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure. (Pubmed Central) - Jul 3, 2021 The prevalence of resistance mutations to lamivudine and emtricitabine in pDNA in a cohort of youths perinatally infected with HIV who remain with undetectable VL, previously lamivudine and/or emtricitabine experienced, was infrequent. Our results indicate that ART including lamivudine or emtricitabine may also be safe and successful in youths with perinatal HIV with previous experience of and resistances to these drugs detected in plasma.
- |||||||||| tenofovir disoproxil fumarate / Generic mfg., probenecid / Generic mfg.
PK/PD data, Journal: Probenecid-Boosted Tenofovir: A PBPK model informed strategy for on-demand HIV pre-exposure prophylaxis. (Pubmed Central) - Jun 22, 2021 This model predicted an increase in TFV plasma exposure by 60%, which was within 15% of the observed clinical PK data, and a 3-fold decrease in renal cells exposure following coadministration of a 600mg TDF dose with 2g probenecid. Compared to multiple-dose regimens, a single-dose PRO-boosted TDF regimen may be effective for HIV PrEP and improve adherence and safety by minimizing TFV-induced nephrotoxicity by reducing TFV accumulation in renal cells.
- |||||||||| tenofovir disoproxil fumarate / Generic mfg., emtricitabine/tenofovir disoproxil fumarate / Generic mfg., emtricitabine / Generic mfg.
Clinical, Journal: Intracellular Tenofovir and Emtricitabine Concentrations in Younger and Older Women with HIV Receiving Tenofovir Disoproxil Fumarate/Emtricitabine. (Pubmed Central) - Jun 22, 2021 BMI was positively associated with IL-6 in both age groups, and negatively associated with TFVdp in women ≤45 years. After adjustment, age remained significant for sCD163, while Black race, BMI, and renal function remained significant for several IMs and ENs, suggesting that factors associated with aging, but not age itself, govern intracellular TDF/FTC pharmacology.
- |||||||||| Isentress (raltegravir) / Merck (MSD)
Journal: Virologic failure after 48 weeks of raltegravir-based regimen in low HIV-1 incidence setting. (Pubmed Central) - Jun 5, 2021 Emergence of primary mutations in the integrase gene can account for virologic failure in less than half of patients on raltegravir-based regimen. Low adherence to treatment, pre-existing accessory mutations, and resistance to reverse transcriptase inhibitors may have some role in virologic outcome.
- |||||||||| emtricitabine / Generic mfg.
Journal: Solubility Data, Solubility Parameters and Thermodynamic Behavior of an Antiviral Drug Emtricitabine in Different Pure Solvents: Molecular Understanding of Solubility and Dissolution. (Pubmed Central) - May 11, 2021 The x values of ECT were estimated maximum in polyethylene glycol-400 (PEG-400; 1.41 × 10), followed by ethylene glycol, Transcutol-HP, propylene glycol, methanol, water, isopropanol, ethanol, 1-butanol, dimethyl sulfoxide, 2-butanol and EA (1.28 × 10) at T = 318.2 K. "Apparent thermodynamic analysis" showed an "endothermic and entropy-driven dissolution" of ECT. Overall, PEG-400 was found as the best/ideal solvent for solubility/miscibility of ECT compared to other solvents studied.
- |||||||||| Journal: Cascade of ART Adherence in Virologically-Suppressed Persons Living with HIV. (Pubmed Central) - Apr 7, 2021
These findings demonstrate a wide range of ART adherence and drug exposure associated with viral suppression, indicating that modern regimens are pharmacologically forgiving. Additional research is needed to understand the biologic effects of variable adherence and drug exposure beyond plasma virologic suppression.
- |||||||||| emtricitabine / Generic mfg.
[VIRTUAL] IN VIVO EVALUATION OF LONG-ACTING BIODEGRADABLE EMTRICITABINE IMPLANTS () - Mar 18, 2021 - Abstract #CROI2021CROI_587; The relevance of human target exposures in rat studies are unclear, but concentrations remained above the reported FTC EC90 for 14, 10 and 7 days for POP1, POP2 and POP3, respectively. Ongoing studies seek to optimise exposures that can be achieved for FTC and POP implants manufactured from other antiretroviral drugs.
- |||||||||| emtricitabine / Generic mfg.
[VIRTUAL] EMTRICITABINE TRIPHOSPHATE IN DRIED BLOOD SPOTS PREDICTS FUTURE VIREMIA IN PWH () - Mar 18, 2021 - Abstract #CROI2021CROI_214; This relationship, although diminished by including TFV-DP in the model, demonstrates the ability of a short-term adherence measure to predict future viremia. The mismatch in FTC-TP in DBS in PWH reporting 100% 3-day adherence suggests PWH who report high recent adherence, but who have an undetectable FTC-TP, could benefit from ART adherence counseling regarding their risk of future viremia.
- |||||||||| tenofovir disoproxil fumarate / Generic mfg., zidovudine / Generic mfg.
Clinical, Journal: Tenofovir resistance in early and long-term treated patients on first-line antiretroviral therapy in eight low- and middle-income countries. (Pubmed Central) - Mar 13, 2021 The mismatch in FTC-TP in DBS in PWH reporting 100% 3-day adherence suggests PWH who report high recent adherence, but who have an undetectable FTC-TP, could benefit from ART adherence counseling regarding their risk of future viremia. Dual resistance to TDF+XTC occurred in more than 40% of the people with viral non-suppression receiving tenofovir-based first-line ART, supporting WHO recommendation to optimize the nucleoside backbone in second-line treatment and cautioning against single drug substitutions in people with unsuppressed VL.
- |||||||||| acyclovir / Generic mfg., emtricitabine / Generic mfg.
PK/PD data, Journal: Physiologically Based Pharmacokinetic Models to Predict Maternal Pharmacokinetics and Fetal Exposure to Emtricitabine and Acyclovir. (Pubmed Central) - Feb 12, 2021 The comparison of different emtricitabine PBPK models suggested an overall similar predictive performance in the third trimester, but the comparison of different approaches for estimating placental drug permeability revealed large differences. These models can enhance the understanding of the PK behavior of renally excreted drugs, which may ultimately inform pharmacotherapeutic decision making in pregnant women and their fetuses.
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