Bone density, microarchitecture and tissue quality after 1 year of treatment with dolutegravir/abacavir/lamivudine

Abstract

Background Bone mineral density (BMD) decreases with ART initiation with a tenofovir disoproxil fumarate-containing regimen, although bone tissue quality increases. The impact of dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC)-based ART initiation on bone health parameters is not clear. Objectives To study the impact of DTG/ABC/3TC-based therapy on bone health parameters in ART-naive individuals with HIV after 48 weeks of treatment. Methods An observational, prospective and analytical study of treatment-naive patients with HIV undergoing a DTG/ABC/3TC-based regimen at 48 week follow-up. Changes in bone strength parameters (BMD, bone microarchitecture and bone tissue quality) were assessed with non-parametric methods. Results Sixteen HIV-infected ART-naive patients starting DTG/ABC/3TC were included. BMD in the lumbar spine showed a significant decrease of −2.25% (P = 0.007) and −4.1% in the femoral neck (P = 0.007). Bone microarchitecture, as measured by trabecular bone score, also decreased significantly by −2.5% (P = 0.03). In contrast, bone quality [bone material strength index (BMi)], as measured by microindentation, significantly increased with respect to baseline after 48 weeks of treatment, showing better bone properties of +6.53% (P < 0.001). No significant changes were found in bone turnover markers. In addition, a positive significant correlation between the CD4/CD8 cell count ratio at baseline and changes in BMSi after 48 weeks of treatment was observed (Spearman’s rho = 0.4974; P = 0.04). Conclusions After a 48 week treatment with DTG/ABC/3TC-based ART, BMD and trabecular bone score decreased while bone tissue quality, as measured by microindentation, improved significantly. The state of the immune system at ART initiation is related to bone quality recovery. An overarching approach to assess bone toxicity in ART-treated patients is needed.

Changes in bone quality after switching from a TDF to a TAF based ART: A pilot randomized study

“…Similarly, after switching from a triple therapy including TDF in virologically suppressed PLWH with low BMD -1.0 T-score at weeks 24 and 48, raltegravir in combination with a boosted PI has also been linked to a significant rise in BMD at both the spine and hip ( 20 ). Similar results have been reported with BIC ( 18 ) or DTG ( 10 ). Consequently, TDF is the most likely responsible of the changes in bone quality reported in this study.…”

“…Interestingly, we found that the switch to a TAF regimen was associated with a significant improvement of bone quality of 5%. This increase is similar to those observed in naïve HIV individuals that start ABC-3TC-based regimen (10) or TDF-based regimen (9).…”

“…Interestingly, we found in a previous study that starting antiretroviral treatment improved bone quality despite the fact that bone mineral density decreased in the first weeks of treatment ( 9 , 10 ) likely as a consequence of the control of the viral replication along with the immune reconstitution. In this study PLWHIV under chronic treatment with a TDF-based therapy experienced a median increase of 5% in BMSi values, showing an improvement in bone quality.…”

“…Sample size was calculated according to previous publications ( 8 – 10 ). Accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 12 participants in each arm were needed to recognize a difference greater than or equal to 5 BMSi units as statistically significant.…”

The anti-HIV drug abacavir stimulates β-catenin activity in osteoblast lineage cells

“…However, it is unclear whether this is due to cessation of TDF or positive effects of ABC and DTG. PLWH initiating ABC ( 13–15 ) or DTG ( 16 ) lose BMD, but this could be due to the rapid rise in CD4+ cells post cART-mediated immune reconstitution. ( 17 ) ABC and DTG are not used in pre-exposure prophylaxis (PrEP), therefore their HIV-independent effects on bone are unknown.…”