The safety profile for DTG 50 mg once daily in INI-naive individuals was comparable to RAL- and DRV/r-containing regimens and generally favorable compared with EFV-containing regimens.

Background: Switching to the 2-drug regimen dolutegravir + rilpivirine demonstrated noninferiority vs continuing a 3-drug or 4-drug current antiretroviral regimen (CAR) at week 48 and maintained high levels of virologic suppression to week 148 in the SWORD studies. We report inflammation and atherogenesis biomarkers postswitch to dolutegravir + rilpivirine.

Aim: SWORD-1 and SWORD-2 phase 3 studies concluded that switching virologically suppressed participants with HIV-1 from their current three-or four-drug antiretroviral regimen (CAR) to the two-drug regimen of once-daily dolutegravir (DTG, 50 mg) and rilpivirine (RPV, 25 mg) was safe, well tolerated and noninferior for maintaining HIV-1 suppression at week 48 and highly efficacious to week 148. A secondary objective was to characterize drug exposure and exposure-efficacy/safety relationships.Methods: Adults with plasma HIV-1 RNA <50 copies/mL were randomized to switch to once-daily DTG + RPV on day 1 or to continue CAR for 52 weeks before switching. Trough plasma concentrations (C0) of DTG and RPV, the proportion of participants with HIV-1 RNA <50 copies/mL and adverse events to week 100 were summarized and subjected to exposure-response analyses in the overall population, in the subset of participants who switched from CAR containing enzyme-inducing drugs and by age category (≥50 and <50 years). The relationship between C0avg (individual average C0 across visits) and efficacy/safety was investigated.Results: Although week 2 DTG and RPV C0 were lower in participants switching from enzyme-inducing antiretroviral drugs, C0 and C0avg stayed above in vitro antiviral protein binding-adjusted IC90 and to week 100 with viral suppression >89%. DTG or RPV C0avg showed no relationship with virologic failures or safety. Participants ≥50 years had similar C0avg and safety response to younger participants. Conclusion:No clinically relevant relationship between DTG or RPV exposures and virologic or safety response was observed, confirming the DTG + RPV switch for participants as a safe and effective treatment.The primary efficacy and safety results of SWORD-1 and SWORD-2, two multicentre phase 3 trials conducted by more than 125 physician investigators in 13 countries, were previously published in Lancet. 1 Dr Josep Llibre and Dr Chien-Ching Hung, the two investigator signatories for the SWORD-1 and SWORD-2 study reports, were the lead authors on the primary manuscript, along with other high enrolling authors. The present manuscript reports on a secondary analysis: the integration of pharmacokinetic (PK) and pharmacodynamic (PD) data from the SWORD studies. The collation of these PK/PD results does not reflect the direct work of physician investigators, therefore the principal investigators are not included as authors of this manuscript.Clinical trial registration: ClinicalTrials.gov, NCT02429791 (SWORD-1) and NCT02422797 (SWORD-2).

BackgroundHIV infection and antiretroviral therapy (ART), particularly tenofovir (TDF), is associated with loss of bone mineral density (BMD). The SWORD studies demonstrated noninferiority of the 2-drug regimen (2DR) dolutegravir (DTG) + rilpivirine (RPV) to continuing current triple-therapy ART (CAR) at 48 weeks and continued viral suppression on DTG+RPV through Week 148. A substudy of SWORD 1 and 2 evaluated a change in BMD by DEXA for those participants who switched from triple ART containing TDF to DTG+RPV. The primary analysis reported at 48 weeks showed a significant increase in total hip and lumbar spine BMD and a significant decrease in bone turnover markers in patients receiving DTG+RPV compared with CAR. Here we present data through Week 148.MethodsHIV-infected adult patients with HIV-1 RNA < 50 c/mL received ART containing TDF for ≥6 months prior to randomization to DTG+RPV (Early Switch group, ES) or CAR on Day 1 (Baseline, BL) through Week 48 in SWORD-1/2. CAR patients suppressed at Week 48 switched to DTG+RPV at Week 52 (Late Switch group, LS). Hip and lumbar spine BMD were measured by DEXA scans read centrally. Secondary endpoints include a change in BMD and bone turnover markers through Week 148.ResultsFollowing switch to DTG+RPV significant increases were observed for total hip in the ES and LS groups through 100 weeks with a non-significant increase at Week 148 in ES (Figure 1a). Lumbar spine BMD significantly increased from BL at 48 weeks post switch, remained increased, though not significantly from BL through Week 148 (Figure 1b). The BMD of the LS group was similar to that of the ES group through 100 weeks exposure. The majority of patients remained in their pre-switch T-score category or improved a category for both hip and spine through Wk148 (Table 1). Through Wk148, BMI increased minimally and bone turnover markers significantly decreased (P < 0.001 to 0.042 across markers) from BL/LS BL except Type I Collagen C-Telopeptide at Wk148 in the LS group (P = 0.279).ConclusionSwitch to the DTG+RPV 2DR was associated with sustained improvements in BMD through Week 148, along with a reduction in bone markers. The favorable effects on skeletal health were observed despite the ageing of study patients and other factors decreasing BMD. A switch to DTG+RPV in suppressed patients provides a robust option for preserving bone health while continuing suppressive HIV treatment. Disclosures All authors: No reported disclosures.

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