EACS2023: 932 Fostemsavir in association with doravirine for the treatment of heavily treatment-experienced (HTE) PLWH with multi-drug resistant (MDR) HIV-1 infection: data from clinical practice P.F. Salvo , R.J. Steiner , A. Sanfilippo , G. Baldin , E. Visconti , A. D'angelillo , F. Raffaelli , A. Dusina , S. Di Giambenedetto , A. Borghetti Università Cattolica del Sacro Cuore, Security and Bioethics Department, Infectious Diseases Section, Rome, Italy, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, UOC Malattie Infettive, Rome, Italy General data Abstract category: Antiretroviral therapy – observational studies Abstract body Purpose: Fostemsavir and doravirine are novel molecules for the treatment of HIV-1 infection. The aim of the study was to evaluate their viroimmunological efficacy and clinical tolerability in clinical practice. Method: Only HTE-PLWH with MDR HIV-1 infection and detectable levels of HIV-1 RNA were selected. We prescribed fostemsavir to these patients, in combination with an optimized background therapy (OBT) containing doravirine and at least 1 other active antiretroviral molecule, collecting clinical and viroimmunological data at baseline (BL) and after 4 and 12 weeks of treatment. Moreover, we quantified the total blood-associated HIV-DNA, as a biomarker of the HIV cellular reservoir, by droplet digital PCR. Results: We enrolled 10 HTE-PLWH. Characteristics of the population N = 10 (100.0%) Gender (n, %) - Male 6 (60.0%) - Female 4 (40.0%) Age, years (Median, IQR) 62.5 (61 - 64.5) Time since HIV diagnosis, years (Median, IQR) 31 (29 - 34) Time of exposure to ART, years (Median, IQR) 28 (26.5 - 30) Zenith HIV-RNA, Log10 cps/mL 5.70 (5.35 - 5.75) Nadir CD4 cells count, cells/mmc 62 (10 - 248) CDC stage C (n, %) 8 (80.0%) After 4 weeks of follow-up one patient (12.5%) achieved virological suppression with target non detectable (TND), while two patients achieved HIV-RNA levels < 30 cp/mL. HIV-DNA decreased in all patients (-0.57 log x 10 PBMC; 95% CI -0.79;-0.35; Wilkoxon matched-pairs signed-rank test p=0.001). A non-statistically significant decrease in CD4 cell count was observed (-108 cells/mL, 95% CI -242; +26; Wilkoxon matched-pairs signed-rank test p=0.383). Two discontinuations occurred after 4 weeks of follow-up, due to treatment-related gastrointestinal side effects. After 12 weeks, HIV-RNA was <30 cp/mL in only 2 participants. HIV-DNA decreased in 4 participants (50%) with a mean decay of -0.28 log x 10 PBMC; 95% CI -0.69; 0.13; Wilkoxon matched-pairs signed-rank test p=0.114). In the other 4 participants HIV-DNA increased (0.13 log x 10 PBMC; 95% CI 0.01; 0.25; Wilkoxon matched-pairs signed-rank test p=0.686). All participants showed a decrease in CD4 cell count, non-statistically significant (-240 cells/mL; 95% CI -414; -66; Wilkoxon matched-pairs signed-rank test p=0.234). Conclusions: Fostemsavir in association with doravirine seemed to show good antiviral potency against MDR HIV-1. However, observations from our experience raise concern due to the apparently unfavourable immunological profile and tolerability, prompting the need for further evaluations. General conditions 1. I confirm that I previewed this abstract and that all information is correct. I accept that the content of this abstract cannot be modified or corrected after the submission deadline and I am aware that it will be published exactly as submitted.: Yes 2. I confirm that the submission of the abstract constitutes my consent to publication (e.g. conference website, programmes, other promotions, etc.). : Yes 3. I herewith confirm that the contact details saved in this system are those of the corresponding author, who will be notified about the status of the abstract. The corresponding author is responsible for informing the other authors about the status of the abstract.: Yes 4. I agree that all data provided may be used (saved, stored, processed, transmitted and deleted) in compliance with the privacy policy to provide the services described.: Yes 1 1 1 2 2 1 2 2 2,1 2 1 2 10 6 10 6 10 6 177
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