Greater change in bone turnover markers for efavirenz/emtricitabine/tenofovir disoproxil fumarate versus dolutegravir + abacavir/lamivudine in antiretroviral therapy-naive adults over 144 weeks.
OBJECTIVE
Antiretroviral therapy initiation has been linked to bone mineral density and bone biomarker changes. We assessed long-term bone turnover biomarker effects over 144 weeks in patients initiating dolutegravir (DTG) + abacavir/lamivudine (ABC/3TC) versus efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF).


METHODS
Patients randomized in SINGLE received DTG (50 mg once daily) + ABC/3TC or fixed-dose combination EFV/FTC/TDF. We evaluated vitamin D serum levels and bone turnover markers (BTMs), including type 1 collagen cross-linked C-telopeptide (CTx), osteocalcin, bone-specific alkaline phosphatase (BSAP), and procollagen type 1 N-terminal propeptide (P1NP), at baseline and weeks 48, 96, and 144.


RESULTS
Among the 833 enrolled patients (68% white, 85% men), baseline median age was 35 years (range 18-85), median CD4 was 338 cells/μl, and median BMI was 24 kg/m. Fifty-three percent of patients smoked, and 6% reported baseline vitamin D use, with no meaningful differences between groups. Relative to baseline, CTx, osteocalcin, BSAP, and P1NP increased; vitamin D decreased in both groups at weeks 48, 96, and 144. Changes from baseline typically peaked at weeks 48 or 96 and for the four analytes, excluding vitamin D, with the EFV/FTC/TDF group having significantly greater changes from baseline at all time points.


CONCLUSIONS
DTG + ABC/3TC in antiretroviral therapy-naive patients resulted in significantly lower increases in BTMs (CTx, osteocalcin, BSAP, P1NP) compared with EFV/FTC/TDF over 144 weeks. The observed changes are consistent with results from other smaller, randomized trials. These differences in BTMs likely correlate with changes in bone mineral density over time.
aUniversity of Pennsylvania, Philadelphia, Pennsylvania bGeorgetown University School of Medicine, Washington, District of Columbia cUniversity of California San Diego Owen Clinic, San Diego, California, USA dGlaxoSmithKline, London, UK eGlaxoSmithKline, Philadelphia, Pennsylvania fGlaxoSmithKline, Research Triangle Park, North Carolina gViiV Healthcare, Research Triangle Park, North Carolina, USA.
Pablo
P
Tebas
Princy
P
Kumar
Charles
C
Hicks
Catherine
C
Granier
Brian
B
Wynne
Sherene
S
Min
Keith
K
Pappa
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects* / Q000379:methods*; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D044967:Serum / Q000737:chemistry; D014807:Vitamin D / Q000097:blood; D055815:Young Adult
D044966:Anti-Retroviral Agents; D015415:Biomarkers; D014807:Vitamin D