Multidisciplinary Collaborative Integrated Management of Increasingly Prominent HIV Complications in the Post-cART Era

L Lin; TS Li

Disclosures

HIV Medicine. 2020;21(11):683-691. 

In This Article

Effects of HIV and cART on Bone Metabolism

People living with HIV are prone to the clinical characteristics of low bone mass and high bone turnover rate due to the virus infection itself and cART. Different ethnic groups differ in fracture rate, bone density and bone structure. We found that, compared with healthy individuals, Chinese HIV-1 patients had lower bone conversion rate and lumbar primordial bone mineral density (BMD) before cART, with further bone loss after cART initiation. BMD of the lumbar spine, femoral neck and total hip in PLWH decreased significantly within 48 weeks of cART, remained stable at 48–96 weeks, and the annual percentage decline ranged from 1.78% to 3.28%. Levels of collagen type 1 cross-linked C-telopeptide (β-CTX) and procollagen type 1 N-terminal propeptide (P1NP) in PLWH were lower at baseline, and both were elevated within 48 weeks of cART and remained stable during the following 48 weeks. Patients with HIV had a higher baseline parathyroid hormone (PTH) and a significant increase within 96 weeks of cART. There was no statistically significant reduction in 25-OH vitamin D (25OHD).[24] The resulting vitamin D deficiency with secondary hyperparathyroidism is common in this population.

The BMD of AIDS patients decreased by 2–6% in the first 2 years after initiation of cART therapy, similar to a 2-year menopause, and the incidence of fracture in this group was 30–70% higher than that in non-infected persons. The effects of TDF on bone may be related to the direct effects on bone cells or the indirect effects of secondary hyperparathyroidism and failure of calcium phosphate homeostasis leading to inadequate bone mineralization.[25] Compared with other nucleoside reverse transcriptase inhibitors, BMD had a 1–2% greater decline in patients undergoing the TDF regimen.[26]

In our study of the treatment-experiment cohort of PLWH in China, we found that, as assessed by CTX, bone resorption was significantly increased in patients undergoing the TDF + LPV/r regimen.[27] The PI is potentially caused by bone loss through either the activation of osteoclasts or the inhibition of osteoblasts.[26] However, we believed that TDF was a major driver of the observed increase in bone resorption. In the treatment-naïve cohort, we found that exposure to TDF-based cART may lead to increasing vitamin D binding protein levels, decreased bioavailability of 25OHD, and increased iPTH compensation.[28] Supplementation with vitamin D may alleviate bone loss associated with the use of ART such as TDF. This is a prospective study being conducted by the CACT to untangle the toxicity of osteoporosis caused by long-term treatment with TDF. The number of PLWH receiving TDF treatment is still increasing in China; however, diagnosis and treatment of osteoporosis and fractures still vary in different regions. Therefore, it is increasingly important to include TDF-based treatment in future studies to assess the impact of cART on bone disease in HIV-infected Chinese patients.

HIV infection and the use of TDF are high-risk factors for fracture; more attention should be given to bone health in these patients. For patients with bone disorders, TDF should be avoided, and ABC can be considered to either replace TDF or a simplified treatment regimen. Moreover, a comprehensive assessment of both bone mass and bone metabolism was conducted in conjunction with endocrinologists to intervene and improve the bone health of patients with AIDS.

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