CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

669

24-Month Outcomes on Second-Line Antiretroviral Therapy in South Africa: A Target Trial Emulation Jennifer A. Brown 1 , Lara Lewis 1 , Yukteshwar Sookrajh 2 , Lungile Hobe 3 , Thulani Ngwenya 4 , Johan van der Molen 1 , Kwabena Asare 1 , Kwena Tlhaku 1 , Mlungisi Khanyile 1 , Thokozani Khubone 2 , Nigel Garrett 1 , Jienchi Dorward 1 1 Centre for the AIDS Programme of Research in South Africa, Durban, South Africa, 2 eThekwini Municipality Health Unit, Durban, South Africa, 3 Mseleni Hospital, Mseleni, South Africa, 4 Bethesda Hospital, Bethesda, South Africa Background: The WHO recommends dolutegravir (DTG) instead of ritonavir boosted lopinavir (LPV/r) in second-line antiretroviral therapy (ART), and recycled tenofovir disoproxil fumarate (TDF)/emtricitabine or lamivudine (XTC) instead of zidovudine (AZT)/XTC as backbone. However, there is little long term data from routine, low-resource settings, where DTG resistance may be emerging. We compared 24-month outcomes with these 3 regimens. Methods: We analysed routinely collected, de-identified data from people with HIV at 125 public primary care clinics in KwaZulu-Natal, South Africa. We emulated a target trial among adults switching to second-line AZT/XTC/LPV/r, AZT/XTC/DTG, or TDF/XTC/DTG between December 2019 and February 2021 after viral failure with TDF/XTC/efavirenz. The co-primary endpoints were i) loss to follow-up (LTFU) including death through 24 months (time-to-event) and ii) viraemia >50 copies/mL at 24 months. We used logistic regression with inverse probability of treatment weights in intention-to-treat (ITT) analyses and with inverse probability of censoring weights in per protocol analyses, with bootstrapped confidence intervals (CIs). Results: Of 2144 people, 917 (42.8%) switched to AZT/XTC/LPV/r, 343 (16.0%) to AZT/XTC/DTG, and 884 (41.2%) to TDF/XTC/DTG. Median age was 36 years (IQR 30-43), 1245 (58.1%) were female and median time with viraemia ≥1000 copies/ mL was 371 days (IQR 235-588). ART changed during follow-up for 24.2%, 24.5%, and 15.4% of those switched to AZT/XTC/LPV/r, AZT/XTC/DTG, and TDF/ XTC/DTG, respectively. In ITT analysis of LTFU (N=2144), the standardised risk was higher with AZT/XTC/LPV/r (33.5%; adjusted risk difference [aRD] 6.7%, 95% CI 0.2 to 12.3; strong evidence) and with TDF/XTC/DTG (32.4%; aRD -5.7%, 95% CI -11.3 to 1.4%; weak evidence) than with AZT/XTC/DTG (26.7%), and similar between AZT/XTC/LPV/r and TDF/XTC/DTG. The standardised risk of viraemia in those retained in care with a VL result (N=1190) was higher with AZT/XTC/LPV/r (48.0%) than AZT/XTC/DTG (39.6%; aRD 8.4%, 95% CI -0.2 to 16.9; weak evidence) or TDF/XTC/DTG (39.0%; aRD 9.0%, 95% CI 2.9 to 15.1; strong evidence), and similar for AZT/XTC/DTG and TDF/XTC/DTG. Per protocol analyses gave similar results ( Table ). Conclusions: Compared with AZT/XTC/LPV/r, people on second-line DTG had less viraemia, with no evidence of worse viraemia with recycled TDF. Interventions to improve LTFU and viraemia with second-line therapy are needed, and drug resistance surveillance remains essential.

670

Dolutegravir With Either Doravirine or Rilpivirine: Two-Drug Antiretroviral Therapy Outcomes Rachel Denyer 1 , Morgan Byrne 2 , Clayton Nance II 1 , Daniel Seeger 1 , Natella Rakhmanina 4 , Anne Monroe 2 , Debra Benator 1 , for the DC Cohort Executive Committee 1 Veterans Affairs Medical Center, Washington, DC, USA, 2 George Washington University, Washington, DC, USA, 3 Children's National Hospital, Washington, DC, USA Background: Dual nucleos(t)ide reverse transcriptase inhibitor (NRTI)-free regimens are an attractive choice for simplification of antiretroviral therapy (ART) in treatment-experienced patients. Fixed-dose formulation of rilpivirine (RPV) plus dolutegravir (DTG) is recommended for ART optimization, while Doravirine (DOR) plus DTG is a more recent NRTI-free option. We aimed to compare virologic suppression (VS) in treatment-experienced persons with HIV following switch to DTG+DOR versus DTG+RPV. Methods: We analyzed DC Cohort study participants ≥18 years during the period Jan 2017-June 2024. Participants with at least 1 year of DC Cohort enrollment were included if prescribed either DTG+DOR or DTG+RPV for ≥60 days. We collected demographics (age, sex, gender, race/ethnicity), chronic kidney disease (CKD) diagnosis, insurance type and viral load data. CD4 count and VS (HIV RNA<200 copies/mL) at regimen initiation was defined as the lab closest to regimen start date (within prior 12 months). In participants with VS pre-switch, Kaplan-Meier curves were used to show the probability of continued VS (HIV RNA<200 copies/mL) from 7 days post-switch until the earliest of 24 months post-switch or regimen cessation. Results: A total of 466 participants were included in the analysis (DTG+DOR group: N = 31; DTG+RPV group: N = 435) with median regimen duration 2.1 years (IQR: 1.0-4.1). The median age was 58.3 years (IQR: 50.5–64.5), and the majority were male (75.8%) and identified as Black (78.8%), with 40.1% with a prior CKD diagnosis. At regimen initiation, VS was observed in 77.4% of the DTG+DOR group versus 86.2% of the DTG+RPV group and median CD4 count was 634 cells/mm³ (IQR: 481–812) in the DTG+DOR group and 595 cells/mm³ (IQR: 432–853) in the DTG+RPV group. DTG+DOR recipients more frequently had public insurance (87.1%) and received care at academic sites (83.9%) than the DTG+RPV group (60.0% and 55.2%, respectively). Among 347 participants with VS at regimen initiation and post-switch VL data, a higher proportion maintained VS on DTG+RPV (308 of 327, 94.1%) compared to DTG+DOR (14 of 20, 70.0%). Log-rank testing indicates a significant difference between Kaplan Meier curves for each regimen (Figure; p= 0.0001). Conclusions: Observed differences in VS following switch to DRG+RPV and DTG+DOR may be due to differences in participant characteristics, adherence, viral resistance patterns, and the dual regimens. Further studies are needed to evaluate efficacy of dual NRTI-free regimens in real-world settings.

Poster Abstracts

671

Is It Effective to Switch Regimen in PWH With Low-Level Viremia in the Current Era? Tommaso Clemente 1 , Pierluigi Reali 1 , Riccardo Lolatto 1 , Girolamo Piromalli 1 , Rebecka Papaioannu Borjesson 1 , Flavia Passini 2 , Diana Canetti 1 , Elena Bruzzesi 2 , Emanuela Messina 1 , Silvia Nozza 2 , Antonella Castagna 1 , Vincenzo Spagnuolo 1 1 IRCCS San Raffaele Scientific Institute, Milan, Italy, 2 San Raffaele Vita-Salute University, Milan, Italy Background: Antiretroviral treatment (ART) management during HIV low level viremia (LLV) is still unclear. Our aim was to evaluate outcomes after LLV in people with HIV (PWH) according to ART switch.

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