CROI 2016 Abstract eBook
Results: In individuals receiving cART with HCV genotype (GT) 1 and 4 (n=92), no clinically significant DDI were expected in 41%with sofosbuvir/ledipasvir, 25%with paritaprevir/ ritonavir/ombitasvir plus dasabuvir, 37%with grazoprevir/elbasvir and 61%with sofosbuvir plus daclatasvir. DDIs requiring DAA or antiretroviral dose adjustment or additional monitoring for toxicity were noted in 34%with sofosbuvir plus daclatasvir, 7%with paritaprevir/ritonavir/ombitasvir plus dasabuvir and 26%with sofosbuvir/ledipasvir. Contra- indicated antiretroviral agents were noted in 47%with paritaprevir/ritonavir/ombitasvir plus dasabuvir and 45%with grazoprevir/elbasvir, but only 5%with sofosbuvir/ledipasvir and 0%with sofosbuvir plus daclatasvir. In individuals receiving cART with HCV GT 2 or 3 (n=45), no clinically significant DDI were expected in 67% and DDI requiring DAA dose adjustment were noted in 33%with sofosbuvir plus daclatasvir, allowing co-administration in 100%. Conclusions: Potential DDIs will impact on DAA prescribing in HIV/HCV co-infection. HCV infection can be safely and successfully treated provided DDI are recognised and managed appropriately. 452 Real-Life Renal Safety of Boosted TDF in HIV/HCV Patients on SOF/LDV M.J. Vivancos-Gallego ; A. Moreno; María Jesús Pérez-Elias; A. Díaz de Santiago; Carmen Quereda-Rodriguez; J.L. Casado; Sara Bañón; M. Sánchez-Conde; M.L. Mateos; Santiago Moreno Hosp Universitario Ramón y Cajal, Madrid, Spain Background: Ledipasvir increases tenofovir (TDF) exposures. In individuals taking EVG/COBI/TDF/FTC or TDF with a ritonavir (RTV)-boosted HIV PI, higher TDF exposures may increase the risk of renal toxicity. Methods: To evaluate the renal safety of 12 or 24 weeks of Sofosbuvir/Ledispasvir (SOF/LDV), according to boosted TDF exposure, in a cohort of 159 HIV/HCV co-infected patients at a tertiary center in Madrid (Spain). We included all consecutive patients with complete renal function and overall safety follow-up data during therapy. Results: FromMarch 2015, 159 patients started SOF/LDV. HAART included TDF/FTC in 53 (33%); of them, 35 (66%) patients did not receive a boosted TDF regimen, whereas a “boosted TDF” regimen was used in 18 (34%): EVG/COBI/FTC/TDF in 10 (55%), FTC/TDF plus a RTV-boosted PI in 7 (39%), and simultaneous EVG/COBI/FTC/TDF and darunavir in one (5%). At baseline there were no significant differences with respect to demographic data, genotype or HCV viral load, eGFR (CKD-EPI), or % of subjects with eGFR<70mil/min. Of note, more patients on boosted TDF received a 24w course of SOF/LDV (28% vs 0%, p=0.005). During therapy we did not find significant differences in Creatinine or eGFR between both groups, nor in the rates of eGFR<70ml/min at the end of SOF/LDV: 2 patients (6%) in the non-boosted TDF group vs 3 patients (17%) in the TDF-boosted group (p=0.32). None of the 53 patients on TDF reached eGFR below 50ml/min, and only one patient on boosted- TDF (5%) stopped TDF due to renal impairment after 74 days of therapy (eGFR 56 ml/min). Conclusions: In our “real life” population, SOF/LDV did not significantly worsen renal function in patients on “boosted TDF” (EVG/COBI/FTC/TDF or TDF with a RTV-boosted HIV PI).
453 Interactions Between ABT-493 Plus ABT-530 Combination and Rilpivirine or Raltegravir Matthew P. Kosloski 1 ; Sandeep Dutta 1 ; Bifeng Ding 1 ; StanleyWang 2 ; Jens Kort 1 ;Wei Liu 1 ; Rajneet K. Oberoi 1 1 AbbVie Inc, North Chicago, IL, USA; 2 AbbVie Inc, Redwood City, CA, USA
Background: ABT‐493 (protease inhibitor discovered by AbbVie and Enanta) and ABT‐530 (NS5A inhibitor) are direct acting antivirals developed as a combination regimen for treatment of chronic hepatitis C virus genotype 1‐6 infection. Rilpivirine, a non‐nucleoside reverse transcriptase inhibitor (NNRTI), and raltegravir, a HIV‐1 integrase inhibitor are often used with other antiretroviral agents in the HIV‐HCV co‐infected population. Phase 1 drug‐drug interaction (DDI) studies were conducted to evaluate pharmacokinetics,tolerability, and safety of ABT‐493 + ABT‐530 co‐administered with rilpivirine or raltegravir. Methods: Both rilpivirine and raltegravir DDI studies utilized open label, randomized, multiple‐dose, non‐fasting study designs. In each study, healthy adult subjects received ABT‐493 300 mg QD + ABT‐530 120 mg QD and rilpivirine 25 mg QD (N=24) or raltegravir 400 mg BID (N=12) alone or in combination. Intensive pharmacokinetic assessments were performed for ABT‐493, ABT‐530, rilpivirine, and raltegravir on multiple days throughout the study. Effects of ABT‐493 + ABT‐530 on rilpivirine or raltegravir pharmacokinetics and vice versa were assessed by a repeated‐measures analysis using SAS. Safety was evaluated via assessment of adverse events, vital signs, ECGs and clinical laboratory tests. Results: Coadministration with multiple ABT‐493 and ABT‐530 doses increased rilpivirine Cmax and AUCinf by 105% and 84%, respectively, relative to rilpivirine alone; raltegravir C max and AUC 12 were increased by 34% and 47%, respectively, relative to raltegravir alone. ABT‐493 and ABT‐530 exposure following multiple QD doses, as determined by C max and AUC 24 , were similar when coadministered with rilpivirine or Raltegravir relative to administration of ABT‐493 + ABT‐530 alone (≤13% difference). All adverse events were mild in severity and assessed as not related to study drugs. No clinically significant vital signs, ECG or laboratory measurements were observed during the course of each study.
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