48 week bone marker changes with Dolutegravir (DTG) plus Abacavir/Lamivudine (ABC/3TC) vs. Tenofovir/Emtricitabine/Efavirenz (EFV/TDF/FTC): the SINGLE trial

  • Y Yazdanpanah
  • M-A Khuong-Josses
  • L Hocqueloux
  • G Pialoux
  • J Durant
  • B Wynne
  • C Granier
  • P Tebas
  • K Pappa
  • S Min
Open Access
Poster presentation

Keywords

Bone Mineral Density Bone Turnover Osteocalcin Bone Turnover Marker Bone Marker 

Background

DTG is a once-daily integrase inhibitor that in combination with ABC/3TC, demonstrated superior efficacy with favorable tolerability over TDF/FTC/EFV (SINGLE study) at 48 weeks. EFV is associated with reduced Vitamin D levels through CYP450 enzyme induction; TDF has been associated with decreased bone mineral density (BMD). Antiretroviral treatment (ART) initiation is characterized by initial rapid decline in bone mineral density (BMD) that subsequently stabilizes. Bone turnover markers are increased during these BMD changes.

Methods

In the double-blind SINGLE study (table 1) we measured markers of bone turnover (bone-specific alkaline phosphatase, C-termial telopeptide type 1 collagen, osteocalcin, and procollagen type 1 N-propeptide) & Vitamin D at baseline (BL) and at 48 weeks. ANCOVA analyses were adjusted for the following factors age, sex, HIV RNA, CD4+ cell count, BL biomarker level, BMI, smoking status, and Vitamin D supplementation.

Table 1

 

DTG+ABC/3TC change from baseline* (N=414)

TDF/FTC/EFV change from baseline* (N=419)

Geometric Mean Ratio**

[95% CI for the ratio] p-value

Bone-specific alkaline phosphatase

15%

60%

0.720

[0.685-0.756] <0.001

C-terminal telopeptide for type 1 collagen

33%

68%

0.789

[0.747-0.832] <0.001

Osteocalcin

22%

48%

0.827

[0.779-0.878] <0.001

Procollagen type 1 N-propeptide

30%

66%

0.784

[0.749- 0.821] <0.001

Vitamin D (25-hydroxy-Vitamin D)

-7%

-10%

1.036

[0.970-1.107] P=0.292

*adjusted percent change from baseline=100 X adjusted geometric mean of (week 48/baseline)-100

**GMR= (DTG+ABC/3TC+100) / (TDF/FTC/EFV+100)

Results

833 subjects were analyzed: 84% males; 68% whites. Mean BL VL: 4.7 log10 c/mL; 32% VL>100,000 c/mL and mean BL CD4 cell count = 350 cells/mm3. Bone markers increased in both groups but the increases were significantly greater in subjects treated with TDF/FTC/EFV. Vitamin D levels decreased in both treatment groups; the differences were not significant between groups.

Conclusions

After 48 weeks, significantly greater changes from baseline were observed for all bone markers in subjects receiving TDF/FTC/EFV, indicating more active bone turnover when compared to changes seen in subjects receiving DTG + ABC/3TC. These differences may correlate with known TDF-associated changes in BMD over time and further study of the potential advantages of a DTG+ABC/3TC regimen appear warranted.

Copyright information

© Yazdanpanah et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors and Affiliations

  • Y Yazdanpanah
    • 1
  • M-A Khuong-Josses
    • 1
  • L Hocqueloux
    • 1
  • G Pialoux
    • 1
  • J Durant
    • 1
  • B Wynne
    • 1
  • C Granier
    • 1
  • P Tebas
    • 1
  • K Pappa
    • 1
  • S Min
    • 1
  1. 1.Bichat Claude-Bernard Hospital - APHPParisFrance

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