EACS2023: 360 Real-world effectiveness and tolerability of doravirine-based antiretroviral therapy in people with HIV: a nationwide matched cohort study P.G.A. Oomen , F.W.N.M. Wit , K. Brinkman , S.M.E. Vrouenraets , T. Mudrikova , B.J. van Welzen , M. van der Valk , on behalf of the ATHENA National Observational Cohort Study University Medical Center Utrecht, Department of Infectious Diseases, Utrecht, Netherlands, Stichting hiv Monitoring, Amsterdam, Netherlands, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Department of Infectious Diseases, Amsterdam, Netherlands, Onze Lieve Vrouwe Gasthuis, Department of Internal Medicine and Infectious Diseases, Amsterdam, Netherlands General data Abstract category: Antiretroviral therapy – observational studies Abstract body Purpose: Assess real-world effectiveness and tolerability of switching to doravirine (DOR)-based triple antiretroviral-therapy(ART) in treatment-experienced people with HIV-1(PWH) with two years follow-up. Method: We conducted a nationwide prospective cohort study of PWH without prior virological failure ≥12 months stable on a non-DOR triple or dual therapy regimen switching to DOR (cases). They were matched 1:2 to individuals continuing a nonDOR regimen. Matching was performed on age, sex, HIV acquisition category, time since ART initiation, calendar time, pre-ART CD4 count, pre-ART HIV-1 RNA plasma viral load (pVL), and class of anchor drug prior to switch. The primary outcome was protocol-defined virological failure (PDVF) (pVL ≥200 cop/mL) with a non-inferiority margin of +5% in the intention to treat (ITT) population at week 104, with participants switching ART or becoming lost to follow-up considered as PDVF. In the on treatment (OT) population, those who switched ART or lost to follow-up were censored from that moment onwards. As secondary outcome, tolerability was assessed. Results: In total, 590 cases and 1180 controls were included (Table 1). Eleven (1.9%) cases and 26 (2.2%) controls had a pVL ≥200 cop/mL during the study. Both in ITT and OT analyses, non-inferiority was reached (ITT risk difference -0.68% (upper limit of the one-sided 95% confidence interval +2.95); OT risk difference -0.46% (upper limit of the one-sided 95% confidence interval +1.05)). All cases with pVL>200 cop/ml re-suppressed without ART switch: no confirmed virological failure (twice pVL ≥200 cop/mL) was observed in them. Hundred-and-five (17.8%) cases and 210 (17.8%) controls switched ART regimen (Fig.1). In 73 (12.4%) cases, DOR was discontinued due to toxicity, with insomnia and nausea the most common adverse effects (both 1.2% of cases). Table 1. Baseline characteristics of cases and controls Cases (n= 590) Controls (n= 1180) p-value Age, years 49.8 (40.8 – 57.3) 49.5 (41.1 – 56.2) 0.476° Sex (at birth) - Female - Male 66 (11.2) 524 (88.8) 132 (11.2) 1048 (88.8) >0.999~ Region of origin* - Netherlands / Western - Sub-Sahara Africa - Caribbean / Latin America - Other 433 (73.4) 31 (5.3) 76 (12.9) 50 (8.5) 887 (75.2) 89 (7.5) 126 (10.7) 78 (6.6) 0.009~ HIV acquisition category* - MSM - Heterosexual - Other 472 (80.0) 96 (16.3) 22 (3.7) 944 (80.0) 193 (16.4) 43 (3.6) >0.999^ Time since HIV diagnosis, years 11.0 (6.8 – 15.2) 10.8 (7.0 - 15.2) 0.861° Time since ART initiation, years 8.9 (5.6 – 12.3) 8.8 (5.7 – 12.3) 0.955° Pre-ART pVL (cop/mL)* 114000 (38800 – 357770) 100000 (37500 -300000) 0.374° Pre-ART CD4 count (cells/mm )* 300.0 (180.0 - 420.0) 291.0 (190.0 - 410.0) 0.899° pVL at study entry (cop/mL) - Detectable, below 200 cop/mL - Undetectable 25 (4.2) 565 (95.8) 49 (4.2) 1131 (95.8) 0.933~ CD4 count at study entry (cells/mm ) 747.0 (568.0 – 959.0) 720.0 (549.0 – 940.0) 0.075° Prior AIDS diagnosis - No - Yes 493 (83.6) 97 (16.4) 977 (82.8) 203 (17.2) 0.687~ History of cardiovascular disease* - No - Yes 570 (96.6) 20 (3.4) 1123 (95.2) 52 (4.4) 0.198^ History of non-AIDS-defining malignancy* - No - Yes 569 (96.4) 21 (3.6) 1128 (95.6) 47 (4.0) 0.306^ Number of prior ART regimens - 0-2 - 3-5 - >5 219 (37.1) 309 (52.4) 62 (10.5) 839 (71.1) 289 (24.5) 52 (4.4) <0.001~ ART class before study inclusion - Dual therapy - INSTI-based triple therapy - NNRTI-based triple therapy - PI-based triple therapy 6 (1.0) 326 (55.3) 202 (34.2) 56 (9.5) 12 (1.0) 652 (55.3) 404 (34.2) 112 (9.5) >0.999~ Reasons for switching to DOR - ART simplification - Cost saving - Toxicity - Other 161 (27.3) 54 (9.2) 218 (36.9) 157 (26.6) NA All categorical data are expressed as number (percentage of total population) and all continuous data are expressed as median (interquartile range). ~ Chi-square test; ^ Fisher`s Exact test; ° Wilcoxon test; # Students` T test * Missing data: region of origin 2 (0.4%) cases and 4 (0.4%) controls; HIV acquisition category 10 (1.7%) cases and 20 (1.7%) controls; pre-ART pVL 55 (9.3%) cases and 19 (3.2%) controls; pre-ART CD4+ count 54 (9.2%) cases and 23 (1.9%) controls; history of cardiovascular disease 5 (0.4%) controls; history of non-AIDS-defining malignancy 5 (0.4%) controls. Abbreviations: AIDS, acquired immunodeficiency syndrome; ART, antiretroviral therapy; cop, copies; DOR, doravirine; INSTI, integrase strand transfer inhibitor, MSM, men who have sex with men; no., number; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor, pVL, plasma viral load; PWH, people with HIV. Conclusions: Switching to DOR-based ART in well-suppressed PWH was non-inferior regarding effectiveness and tolerability compared with matched PWH on non-DOR regimens after two years in a real-world setting. 1 2,3 4 4 1 1 2,3 1 2 3 4 + + 3 + 3
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