Comparison of Bone and Renal Effects In HIV-infected Adults Switching to Abacavir or Tenofovir Based Therapy in a Randomized Trial

Abstract

IntroductionOur objective was to compare the bone and renal effects among HIV-infected patients randomized to abacavir or tenofovir-based combination anti-retroviral therapy.MethodsIn an open-label randomized trial, HIV-infected patients were randomized to switch from zidovudine/lamivudine (AZT/3TC) to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). We measured bone mass density (BMD) and bone turnover biomarkers (osteocalcin, osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), alkaline phosphatase, type I collagen cross-linked C-telopeptide (CTx), and osteoprotegerin). We assessed renal function by estimated creatinine clearance, plasma cystatin C, and urinary levels of creatinine, albumin, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL). The changes from baseline in BMD and renal and bone biomarkers were compared across study arms.ResultsOf 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. BMD was measured in 33, 26, and 27 patients at baseline, week 24, and week 48, respectively. In TDF/FTC-treated patients we observed significant reductions from baseline in hip and lumbar spine BMD at week 24 (−1.8% and −2.5%) and week 48 (−2.1% and −2.1%), whereas BMD was stable in patients in the ABC/3TC arm. The changes from baseline in BMD were significantly different between study arms. All bone turnover biomarkers except osteoprotegerin increased in the TDF/FTC arm compared with the ABC/3TC arm, but early changes did not predict subsequent loss of BMD. Renal function parameters were similar between study arms although a small increase in NGAL was detected among TDF-treated patients.ConclusionSwitching to TDF/FTC-based therapy led to decreases in BMD and increases in bone turnover markers compared with ABC/3TC-based treatment. No major difference in renal function was observed.Trial registrationClinicaltrials.gov NCT00647244

Renal Concerns in the Treatment of Chronic Hepatitis B with Tenofovir

“…New markers of tubular dysfunction, such as neutrophil gelatinase-associated lipocalin (NGAL), may be used to evaluate kidney damage during TDF therapy (40)(41)(42). In the past, various studies have been published demonstrating the usefulness of NGAL as an early biomarker of tubular damage in HIV-infected patients treated with TDF (43)(44)(45)(46). Conversely, the body of evidence in HBV patients, at present, is equivocal.…”

Switching antiretroviral regimes for the treatment of HIV: safety implications

“…However, TDF is currently the antiretroviral drug most associated with BMD loss. [37,42,43]. Results from several randomized clinical trials among antiretroviral naive patients have shown that initiation of cART is associated with a decrease in bone mineral density (BMD) of 2%-6% at both the hip and the spine, which occurs within the first year of treatment, with stabilization thereafter [40,[43][44][45][46][47][48][49].…”

“…Results from several randomized clinical trials among antiretroviral naive patients have shown that initiation of cART is associated with a decrease in bone mineral density (BMD) of 2%-6% at both the hip and the spine, which occurs within the first year of treatment, with stabilization thereafter [40,[43][44][45][46][47][48][49]. Three trials directly compared TDF/FTC with ABC/3TC and found greater decreases in BMD with TDF/FTC-based treatment [40,43,48]. Also, in a randomized clinical trial with patients with osteoporosis or osteopaenia, switching from TDF to ABC was followed by an increase of BMD in femur but not in spine [1,37].…”

Bone Disease in HIV: Recommendations for Screening and Management in the Older Patient

“…Multiple randomized ART trials have documented significantly greater bone loss in patients initiating, or switching to, a tenofovir disoproxil fumarate (tenofovir DF)-containing ART regimen [30][31][32][33][34][35][36] compared with abacavir-containing regimens. In those with low BMD, switching from tenofovir DF to a raltegravir-containing regimen was associated with an increase in BMD [37].…”