Title

Durable suppression 2 years after switch to DTG+RPV 2-drug regimen: SWORD 1&2 studies

Presenter

Michael Aboud

Authors

M. Aboud¹, C. Orkin², D. Podzamczer³, J. Bogner⁴, D. Baker⁵, M.-A. Khuong-Josses⁶, D. Parks⁷, K. Angelis⁸, L. Kahl¹, E. Blair⁹, M. Underwood⁹, B. Wynne⁹, K. Vandermeulen¹⁰, M. Gartland⁹, K. Smith⁹

Institutions

¹ViiV Healthcare, Brentford, United Kingdom, ²Royal London Hospital, London, United Kingdom, ³Ciudad Sanitaria y Universitaria de Bellvitge, Barcelona, Spain, ⁴Leiter der Sektion Klinische Infektiologie, Munich, Germany, ⁵East Sydney Doctors, Sydney, Australia, ⁶CHG - Hôpital Delafontaine, Saint Denis Cedex, France, ⁷Central West Clinical Research, St Louis, United States, ⁸GlaxoSmithKline, Stockley Park, United Kingdom, ⁹ViiV Healthcare, Research Triangle Park, United States, ¹⁰Janssen Pharmaceutica, Beerse, Belgium

Background: Reducing long-term cumulative toxicity becomes more important in an era of near normal life expectancy for PLWHIV. Treatment modalities that reduce long term cumulative ARV exposure in the form of 2-drug regimens (2DR) are an area of active research. At 48 weeks, efficacy of DTG+RPV as a 2DR for maintenance of virologic suppression was non-inferior to 3DRs in SWORD 1&2. Improvements in bone, renal biomarkers and neutral effects on inflammatory biomarkers were demonstrated. We summarize outcomes through week 100.
Methods: Two identical open-label, global, phase III, non-inferiority studies evaluated efficacy and safety of switching from CAR to DTG+RPV once daily in HIV-1-infected adults, with HIV-1 RNA< 50c/mL (VL< 50c/mL) for >6 months and no history of virologic failure. Participants were randomized 1:1 to switch immediately to DTG+RPV (Early Switch group) or continue CAR. Participants randomised to CAR with confirmed suppression at Week (Wk)48 switched to DTG+RPV at Wk52 (Late Switch group). Secondary endpoints included proportion of participants with VL< 50c/mL at Wk100 using Snapshot algorithm for ITT exposed (ITTe) population and safety evaluations.
Results: 1024 participants were randomized and exposed (DTG+RPV 513; CAR 511), across both studies. At Wk100 in the Early Switch group, 456 (89%) had VL < 50c/mL; low rate of snapshot virologic non-response was observed (3%); 6 (1.2%) participants met Confirmed Virologic Withdrawal (CVW) criterion. The Early Switch group demonstrated a stable safety profile consistent with each individual component; 34 participants (7%) experienced AEs leading to withdrawal. At Wk100 in Late Switch group, 444 (93%) had VL < 50c/mL; 2 (< 1%) participants met CVW criterion. Safety profile of the Late Switch group was comparable to the Early Switch group at Wk48 (Table 1). One participant with RPV resistance at CVW (Early Switch group, Wk100) had pre-existing NNRTI mutations at baseline. No participants developed INSTI resistance.
Conclusions: The novel once daily 2DR of DTG+RPV demonstrated durable maintenance of HIV suppression through Week 100, following switch from 3DR in virologically suppressed HIV-1-infected adults. The safety profile of DTG+RPV was consistent with their respective labels. A DTG+RPV 2DR offers potential for reduction in cumulative ARV exposure, without increased risk of virologic failure.

[Pooled SWORD-1 and SWORD-2 Efficacy and Key Safety Results at Week 100 (ITTe) ]

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