Dataset Information

Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine.

ABSTRACT: Those receiving tenofovir/emtricitabine (TDF-FTC) had greater bone loss compared with abacavir/lamivudine (ABC-3TC) in a randomized simplification trial (STEAL study). Previous studies associated increased bone turnover and bone loss with initiation of antiretroviral treatment, however it is unclear whether change in bone mineral density (BMD) was a result of specific drugs, from immune reconstitution or from suppression of HIV replication. This analysis determined predictors of BMD change in the hip and spine by dual-energy x-ray absorptiometry in virologically suppressed participants through week 96.Bone turnover markers (BTMS) tested were: formation [bone alkaline phosphatase, procollagen type 1 N-terminal propeptide (P1NP)]; resorption (C-terminal cross-linking telopeptide of type 1 collagen [CTx]); and bone cytokine-signalling (osteoprotegerin, RANK ligand). Independent predictors of BMD change were determined using forward, stepwise, linear regression. BTM changes and fracture risk (FRAX®) at week 96 were compared by t-test. Baseline characteristics (n = 301) were: 98% male, mean age 45 years, current protease-inhibitor (PI) 23%, tenofovir/abacavir-naïve 52%. Independent baseline predictors of greater hip and spine bone loss were TDF-FTC randomisation (p ? 0.013), lower fat mass (p-trend ? 0.009), lower P1NP (p = 0.015), and higher hip T score/spine BMD (p-trend ? 0.006). Baseline PI use was associated with greater spine bone loss (p = 0.004). TDF-FTC increased P1NP and CTx through Wk96 (p<0.01). Early changes in BTM did not predict bone loss at week 96. No significant between-group difference was found in fracture risk.Tenofovir/emtricitabine treatment, lower bone formation and lower fat mass predicted subsequent bone loss. There was no association between TDF-FTC and fracture risk.

SUBMITTER: Haskelberg H

PROVIDER: S-EPMC3376146 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine.

Haskelberg Hila H Hoy Jennifer F JF Amin Janaki J Ebeling Peter R PR Emery Sean S Carr Andrew A STEAL Study Group

PloS one 20120615 6

<h4>Background</h4>Those receiving tenofovir/emtricitabine (TDF-FTC) had greater bone loss compared with abacavir/lamivudine (ABC-3TC) in a randomized simplification trial (STEAL study). Previous studies associated increased bone turnover and bone loss with initiation of antiretroviral treatment, however it is unclear whether change in bone mineral density (BMD) was a result of specific drugs, from immune reconstitution or from suppression of HIV replication. This analysis determined predictors ...[more]

PMID: 22719882

Similar Datasets

Project description:BackgroundThe use of fixed-dose combination nucleoside reverse-transcriptase inhibitors (NRTIs) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 (HIV-1) infection, but which NRTI combination has greater efficacy and safety is not known.MethodsIn a randomized, blinded equivalence study involving 1858 eligible patients, we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection: abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine plus efavirenz or ritonavir-boosted atazanavir. The primary efficacy end point was the time from randomization to virologic failure (defined as a confirmed HIV-1 RNA level > or = 1000 copies per milliliter at or after 16 weeks and before 24 weeks, or > or = 200 copies per milliliter at or after 24 weeks).ResultsA scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy, according to the NRTI combination, among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more. At a median follow-up of 60 weeks, among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the time to virologic failure was significantly shorter in the abacavir-lamivudine group than in the tenofovir DF-emtricitabine group (hazard ratio, 2.33; 95% confidence interval, 1.46 to 3.72; P<0.001), with 57 virologic failures (14%) in the abacavir-lamivudine group versus 26 (7%) in the tenofovir DF-emtricitabine group. The time to the first adverse event was also shorter in the abacavir-lamivudine group (P<0.001). There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48.ConclusionsIn patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the times to virologic failure and the first adverse event were both significantly shorter in patients randomly assigned to abacavir-lamivudine than in those assigned to tenofovir DF-emtricitabine. (ClinicalTrials.gov number, NCT00118898.)

Project description:BackgroundTherapy with tenofovir is associated with lower bone mineral density (BMD), higher markers of bone turnover and increased fracture risk in HIV-infected adults. Bone structural parameters generated by hip structural analysis may represent a separate measure of bone strength, but have not been assessed in HIV.MethodsDual-energy X-ray absorptiometry (DXA) scans from 254 HIV-infected adults randomised to simplify their existing dual nucleoside analogue reverse transcriptase inhibitor therapy to coformulated tenofovir-emtricitabine or abacavir-lamivudine were analysed using DXA-derived hip structural analysis software. Hip structural parameters included femoral strength index, section modulus, cross-sectional area, and cross-sectional moment of inertia. We used one-way ANOVA to test the relationship between nucleoside analogue type at baseline and structural parameters, multivariable analysis to assess baseline covariates associated with femoral strength index, and t-tests to compare mean change in structural parameters over 96 weeks between randomised groups.ResultsParticipants taking tenofovir at baseline had lower section modulus (-107.3 mm2, p = 0.001), lower cross-sectional area (-15.01 mm3, p = 0.001), and lower cross-sectional moment of inertia (-2,036.8 mm4, p = 0.007) than those receiving other nucleoside analogues. After adjustment for baseline risk factors, the association remained significant for section modulus (p = 0.008) and cross-sectional area (p = 0.002). Baseline covariates significantly associated with higher femoral strength index were higher spine T-score (p = 0.001), lower body fat mass (p<0.001), lower bone alkaline phosphatase (p = 0.025), and higher osteoprotegerin (p = 0.024). Hip structural parameters did not change significantly over 96 weeks and none was significantly affected by treatment simplification to tenofovir-emtricitabine or abacavir-lamivudine.ConclusionIn this population, tenofovir use was associated with reduced composite indices of bone strength as measured by hip structural analysis, but none of the structural parameters improved significantly over 96 weeks with tenofovir cessation.Trial registrationClinicalTrials.gov NCT00192634.

Project description:In the United States, emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) is a preferred nucleoside reverse transcriptase inhibitor (NRTI) backbone with lamivudine/abacavir (3TC/ABC) as a commonly used alternative. For patients infected with human immunodeficiency virus (HIV-1) virologically suppressed on a boosted protease inhibitor (PI) + 3TC/ABC regimen, the merits of switching to FTC/TDF as the NRTI backbone are unknown.SWIFT was a prospective, randomized, open-label 48-week study to evaluate efficacy and safety of switching to FTC/TDF. Subjects receiving 3TC/ABC + PI + ritonavir (RTV) with HIV-1 RNA < 200 c/mL ?3 months were randomized to continue 3TC/ABC or switch to FTC/TDF. The primary endpoint was time to loss of virologic response (TLOVR) with noninferiority measured by delta of 12%. Virologic failure (VF) was defined as confirmed rebound or the last HIV-1 RNA measurement on study drug ?200 c/mL.In total, 311 subjects were treated in this study (155 to PI + RTV + FTC/TDF, 156 to PI + RTV + 3TC/ABC). Baseline characteristics were similar between the arms: 85% male, 28% black, median age, 46 years; and median CD4 532 cells/mm(3). By TLOVR through week 48, switching to FTC/TDF was noninferior compared to continued 3TC/ABC (86.4% vs 83.3%, treatment difference 3.0% (95% confidence interval, -5.1% to 11.2%). Fewer subjects on FTC/TDF experienced VF (3 vs 11; P = .034). FTC/TDF showed greater declines in fasting low-density lipoproteins (LDL), total cholesterol (TC), and triglycerides (TG) with significant declines in LDL and TC beginning at week 12 with no TC/HDL ratio change. Switching to FTC/TDF showed improved NCEP thresholds for TC and TG and improved 10-year Framingham TC calculated scores. Decreased estimated glomerular filtration rate [corrected] (eGFR) was observed in both arms with a larger decrease in the FTC/TDF arm.Switching to FTC/TDF from 3TC/ABC maintained virologic suppression, had fewer VFs, improved lipid parameters and Framingham scores but decreased eGFR. CLINICALTRIALS.GOV IDENTIFIER: NCT00724711.

Dataset Information

Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine.

Publications

Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets