Greater change in bone turnover markers for efavirenz/emtricitabine/tenofovir disoproxil fumarate versus dolutegravir + abacavir/lamivudine in antiretroviral therapy-naive adults over 144 weeks
| Autor: | Charles B. Hicks, Pablo Tebas, Catherine Granier, Sherene Min, Princy Kumar, Keith A. Pappa, Brian Wynne |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Oncology
Adult Male Serum medicine.medical_specialty Efavirenz Bone density Adolescent Immunology Osteoporosis osteocalcin HIV Infections Pharmacology Emtricitabine Bone remodeling chemistry.chemical_compound bone markers Young Adult Abacavir Internal medicine Antiretroviral Therapy Highly Active medicine Immunology and Allergy Humans Vitamin D Aged Aged 80 and over business.industry abacavir efavirenz Abacavir/Lamivudine Clinical Science Middle Aged medicine.disease tenofovir dolutegravir Infectious Diseases chemistry Anti-Retroviral Agents Dolutegravir Female Bone Remodeling business Biomarkers medicine.drug |
| Zdroj: | AIDS (London, England) |
| ISSN: | 1473-5571 0269-9370 |
| Popis: | Understanding long-term consequences of exposure to individual antiretroviral therapy (ART) components is important in making an initial HIV treatment selection. Initiation of ART is associated with a decrease in bone mineral density (BMD). This initial bone loss is greater with some antiretrovirals, in particular, protease inhibitors [1–4] and tenofovir disoproxil fumarate (TDF) [1,5–9]. The impact on bone health of the integrase strand transfer inhibitor (INSTI) class has not been well characterized. Few studies to date have evaluated the effects of INSTI-containing regimens [either raltegravir (RAL) or elvitegravir] on bone composition over 48 weeks or longer. BMD outcomes tended to be more favorable when RAL was administered as part of a protease inhibitor-sparing or TDF-sparing regimen [6,10–12]; elvitegravir was administered as part of a TDF-containing fixed-dose combination and showed similar decreases in BMD as a TDF-containing, protease inhibitor-based comparator regimen [13]. Dolutegravir (DTG) is the most recently approved INSTI, and no studies to date have evaluated long-term changes in BMD in individuals initiating a DTG-based regimen. Measuring BMD in large, randomized trials is complex, as many sites do not have access to appropriate radiological facilities. As a consequence, most studies of BMD are done by monitoring changes after initiation of ART in a subset of the larger study, limiting the generalizability of conclusions and the participation to individuals seen in tertiary medical centers in the developed world. Bone remodeling occurs throughout life. Changes in biochemical markers of bone remodeling [e.g. both resorption markers: type 1 collagen cross-linked C-telopeptide (CTx) and urinary N-telopeptide; and formation markers: serum bone-specific alkaline phosphatase (BSAP), osteocalcin, and procollagen type 1 N-terminal propeptide (P1NP)] can be used to predict the risk of fracture independently from bone density and the rapidity of bone loss in patients with untreated osteoporosis [14]. In the ASSERT study (NCT00549198), which compared abacavir/lamivudine (ABC/3TC) with TDF/emtricitabine (FTC) administered with efavirenz (EFV), results showed a significantly greater decline in BMD and a significant increase in bone turnover markers (BTMs) in the TDF/FTC arm over 96 weeks [8]. Changes in bone markers have been associated with changes in BMD in HIV-positive individuals: in the RADAR study (NCT00677300) and SMART Body Composition substudy (NCT00027352), early increases in CTx, osteocalcin, BSAP, or P1NP predicted decreases in BMD at 48 weeks [6,15]. The objective of this analysis is to evaluate the changes in BTMs in the SINGLE study (ING114467) through 144 weeks of treatment with either DTG + ABC/3TC or EFV/FTC/TDF. |
| Databáze: | OpenAIRE |
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