P166

Dolutegravir, emtricitabine/tenofovir alafenamide fumarate absorption in a gastrectomized HIV-positive patient

C. Alcantarini, M. Ferrara, M. Tettoni, F. Lipani, S. Biffi, A. Di Stefano, M. Trunfio, A. Lazzaro, V. Avataneo, J. Cusato, A. De Nicolò, A. D’Avolio, A. Calcagno, G. Di Perri and S. Bonora. Unit of Infectious Diseases, Department of Medical Sciences, University of Turin Background o The absorption of orally delivered antiretroviral (ARV) drugs depends on several factors such as gastrointestinal motility and gastric pH [1]. o Limited data are available in literature about the absorption of ARV agents, when gastric surface is widely reduced because of gastric surgery as gastrectomy [2]. o Aim of our study was to investigate Dolutegravir (DTG)+Emtricitabine/Tenofovir alafenamide fumarate (F/TAF) plasma exposure in a gastrectomized HIV-patient due to gastric adenocarcinoma.

Materials and methods o We report a case of a 59-year-old HIV positive man followed in our Outpatient Clinic since 1989, with a good immunovirological profile (CD4+ T cells : 889/mcl; 35.5%, ratio 0.8; HIV-RNA undetectable). o He was affected by an infiltrative and ulcerated adenocarcinoma of the stomach and for this reason switched to DTG+F/TAF due to lack of drug-drug interactions (DDIs) with chemotherapy. o The patient underwent a 4/5 gastrectomy with consequent total parenteral nutrition and parenteral medication for few days and nasogastric tube positioned for about a week. o Ten days after nasogastric tube removal, with natural resumption of feeding and oral intake of antiretroviral therapy, the patient was monitored with determination of 12 hours-plasmatic DTG (plDTG), FTC (plFTC), tenofovir (plTFV) and TAF (plTAF) concentrations (C12) using mass spectrometry (UHPLC-MS/MS) FDA and EMA validated method. Results plDTG, plFTC, plTFV and plTAF C12 resulted to be respectively o Table 1 ARVs plasmatic concentrations (ng/mL) 3051 ng/mL, 210 ng/mL, 5 ng/mL and 1 ng/mL, comparable to those reported in literature [3-5]. Drug C12 Reference range o No other comorbidities were reported: normal liver function, BMI 25 DTG 3051 2120 kg/m2 and normal renal function (eGFR:97.8 mL/min/1.73 m² according to CKD-EPI calculator). FTC 210 180

o Moreover, no potential DDIs between ARVs and his concomitant TFV 5 10 medication (Rosuvastatin, Ramipril, Aspirin, Bisoprolol) were observed. TAF 1 ≤1 o After one month, viral load was still undetectable with good tolerability of ARV regimen.

Conclusions o In patients with gastrectomy, ARVs absorption could be unpredictable. This is the first DTG and F/TAF evaluation of in the context of gastrectomy due to an oncological disease. o In this case ARVs plasma exposure was adequate to maintain an immunovirological response. o More data are needed to better investigate other ARV regimens recently available in combined fixed dose, not only in the oncological setting, but also in other conditions affecting gastric absorption (i.e. bariatric surgery). References

1. Schanker LS, Shore PA, Brodie BB, Hogben CAM. Absorption of drugs from the stomach. J Pharmacol 1957;120:528-539 2. Boffito M, Lucchini A, Maiello A, Dal Conte I, Hoggard PG, Back DJ, Di Perri G. Lopinavir/ritonavir absorption in a gastrectomized patient. AIDS 2003;17(1):136-137 3. https://www.hiv-druginteractions.org/prescribing-resources Dolutegravir and emtricitabine fact sheets 4. Vemlidy Summary of Product Characteristics, Gilead Sciences. Dec 2017 and subsequent versions 5. Begley B, Das M, Zhong L, Ling J, Kearney BP, Custodio JM, PhD Pharmacokinetics of tenofovir alafenamide when coadministered with other HIV antiretrovirals J Acquir Immune Defic Syndr 2018;78 (4):465-472