Bone mineral density changes in protease inhibitor-sparing vs. nucleoside reverse transcriptase inhibitor-sparing highly active antiretroviral therapy: data from a randomized trial*

Abstract

ObjectiveThe aim of the study was to compare changes in bone mineral density (BMD) over 144 weeks in HIVinfected patients initiating nucleoside reverse transcriptase inhibitor (NRTI)-sparing or protease inhibitor-sparing highly active antiretroviral therapy (HAART). MethodsSixty-three HAART-naïve patients were randomized to zidovudine/lamivudine 1 efavirenz or lopinavir/ritonavir 1 efavirenz. We performed dual energy X-ray absorptiometry (DEXA) at baseline and at weeks 24, 48, 96 and 144 to evaluate lumbar spine and femoral neck (hip) BMD. ResultsAt baseline, 33 patients (55.9%) had low BMD (T-score o À 1.0) and of these eight had osteoporosis (T-score o À 2.5). Spine BMD declined in both arms until week 24, before stabilizing. In the NRTIsparing arm, the mean percentage change from baseline was À 2.7% [95% confidence interval (CI) À 3.9 to À 1.4] at week 24 and À 2.5% (95% CI À 5.4 to 0.3) at week 144, compared with À 3.2% (95% CI À 4.4 to À 2.1) and À 1.9% (95% CI À 3.5 to À 0.3) in the protease inhibitor-sparing arm. Hip BMD declined until week 48 before stabilizing. In the NRTI-sparing arm, BMD had decreased by À 5.1% (95% CI À 7.1 to À 3.1) at week 48 and À 4.5% (95% CI À 6.9 to À 2.1) at week 144, compared with À 6.1% (95% CI À 8.2 to À 4.0) and À 5.0% (95% CI À 6.8 to À 3.1) in the protease inhibitor-sparing arm. There were no significant differences between arms. Low baseline CD4 cell count was independently associated with spine (P 5 0.007) and hip (P 5 0.04) BMD loss and low body mass index with hip BMD loss (P 5 0.03). ConclusionSpine and hip BMD declined rapidly 24 to 48 weeks after initiating HAART, independent of the assigned drug class, but thereafter BMD values remained stable.Keywords: bone mineral density, highly active antiretroviral therapy, HIV, nucleoside reverse transcriptase inhibitors, osteoporosis, protease inhibitors IntroductionThe introduction of highly active antiretroviral therapy (HAART) has altered the morbidity and mortality of HIVinfected patients substantially. Younger persons diagnosed with HIV infection may face more than 30 years of antiretroviral treatment [1], and therefore it has become increasingly important to understand the potential longterm toxicities associated with HAART. Correspondence: Dr Ann-Brit Hansen, Department of Infectious Diseases M5132, Copenhagen University Hospital, Blegdamsvej 9, Rigshospitalet, 2100 Copenhagen, Denmark. Tel: +45 30299306; e-mail: ann-brit.eg. hansen@rh.regionh.dk DOI: 10.1111DOI: 10. /j.1468DOI: 10. -1293DOI: 10. .2010 (2011), 12, 157-165 157.x r 2010 British HIV Association HIV MedicineIt is well documented that the prevalence of osteopenia and osteoporosis is increased in HIV-infected persons. In a recent review it was estimated that up to two-thirds of all HIV-infected patients have reduced bone mineral density (BMD), and 15% have osteoporosis as defined by a T-score of o2.5. Compared with an HIV-negative person, an HIVinfected person is 3-to-4 times more likely to have osteoporosis, and some data indicate that the prevalence...

Effects of vitamin D deficiency and combination antiretroviral therapy on bone in HIV-positive patients

“…In Simplification with fixed-dose Tenofovir-Emtricitabine or AbacavirLamivudine in adults with suppressed HIV replication, a cART simplification study in patients with undetectable HIV RNA levels, reductions in BMD were observed in patients randomized to tenofovir/emtricitabine, with improvements in the abacavir/lamivudine arm; osteopenia and osteoporosis were encountered at a higher rate in the tenofovir/emtricitabine arm (8.54 vs. 4.37 events per 100 person-years in the abacavir/lamivudine arm) [44]. Rapid reductions of 2-6% in BMD during the first 24-48 weeks, with subsequent stabilization or improvement up to 192 weeks, have been observed in several studies comparing different cART regimens [28,49,[57][58][59][60][61]. Greater reductions in spine and hip BMD at 48 and/or 96 weeks were observed in patients randomized to tenofovir/emtricitabine versus abacavir/lamivudine [49,57], atazanavir/ritonavir versus efavirenz [57], and lopinavir/ritonavir/zidovudine/lamivudine versus lopinavir/ritonavir/nevirapine [28].…”

An increased risk of osteoporosis in a HIV-infected patient in the era of HAART. Case report analysis

“…Available data suggest that while BMD may initially decline modestly after the start of HAART, there is then a gradual recovery in BMD over time. This may reflect the observation that BMD declines as HIV diseases progress and that this decline may be stopped and probably gradually corrected with successful HAART [21,22]. A recent study shows that patients taking HAART are at increased risk of developing osteopenia and osteporosis [23].…”

Switching antiretroviral regimes for the treatment of HIV: safety implications

“…[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]. Three trials directly compared TDF/FTC with ABC/3TC and found greater decreases in BMD with TDF/FTC-based treatment [40,43,48].…”