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Background: Loss of bone mineral density (BMD) has been attributed to traditional risk factors for osteoporosis, HIV infection and antiretroviral therapy (ART), in particular tenofovir (TDF). 202094, a sub-study of the international, multicenter SWORD 1 & 2 studies, evaluated change in BMD (by DEXA) following switch from a triple ART regimen containing TDF to the 2-drug regimen (2DR) dolutegravir (DTG) + rilpivirine (RPV). Week 48 SWORD data demonstrated maintenance of suppression with DTG+RPV and noninferiority to continuing current ART (CAR).
Methods: Subjects were HIV-infected adults, with HIV-1 RNA< 50c/mL and who received ART containing TDF both for ≥ 6 months prior to randomization to DTG+RPV or CAR on Day 1 through Week 48 in SWORD-1/2. Hip and lumbar spine BMD were measured by DEXA scans which were centrally read. The primary endpoint was the percentage change in total hip BMD. Secondary endpoints included change in lumbar spine BMD and bone turnover markers. The ANCOVA BMD analysis of the intent-to-treat population adjusted for baseline parameters (see Table 1).
Results: The results at Week 48 are shown in Table 1. DTG + RPV patients had an increase from Baseline to Week 48 in hip (1.34%) and spine BMD (1.46%) which differed statistically significantly (p=0.014, p=0.039, respectively) from CAR patients. (Table 1). Consistent with this, DTG + RPV patients had a decrease from Baseline to Week 48 in bone specific alkaline phosphatase, procollagen type 1-N-propeptide, osteocalcin and Type I Collagen C-Telopeptide bone turnover markers which differed statistically significantly from the CAR group (p range from < 0.001 to 0.029 across markers).

Treatment Assignment in Parent SWORD StudyDTG + RPVCARp value
Evaluable subjects at Baseline and Week 48(a)4635 
Primary Endpoint: Total Hip(b) BMD
Mean adjusted % change from Baseline to Week 48 (95% CI)(c)1.34 (0.68, 2.01)0.05 (-0.71, 0.82) 
Difference in adjusted % change from Baseline to Week 48 between treatment groups (95% CI) and p value(c)1.29 (0.27, 2.31)p = 0.014
Secondary Endpoint: Lumbar Spine(d)BMD
Mean adjusted % change from Baseline to Week 48 (95% CI)(c)1.46 (0.65, 2.28)0.15 (-0.79, 1.09) 
Difference in adjusted % change from Baseline to Week 48 between treatment groups (95% CI) and p value(c)1.32 (0.07, 2.57)p = 0.039
a. Subjects having evaluable BMD data at both Baseline and Week 48 had their DEXA scans performed within the predefined time period for the study visit b. Total hip includes the femoral neck, trochanter and intertrochanter areas c. BMD is expressed as areal density. Estimates and associated p-values are from an ANCOVA model adjusted for Baseline BMD value, age at study entry, and Baseline BMI d. Lumbar spine includes the first lumbar vertebra (L1) to the fourth lumbar vertebra (L4)
[202094 Week 48 Results: ITT-Exposed Population]


Conclusions: Switch to the 2 drug-regimen of DTG+RPV is associated with significant improvement in bone mineral density and markers of bone health compared to continuation of a TDF-based 3 drug regimen, and provides a robust option for preserving bone health while continuing suppressive HIV treatment.