Changes in Bone Mineral Density After 96 Weeks of Treatment With Atazanavir/Ritonavir or Lopinavir/Ritonavir Plus Tenofovir DF/Emtricitabine in Treatment-Naive Patients With HIV-1 Infection

Moyle, Graeme; Hardy, Hélène; Farajallah, Awny; McGrath, St John; Kaplita, Stephen; Ward, Douglas J.

doi:10.1097/qai.0000000000000383

Cited by 10 publications

(8 citation statements)

References 35 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Investigators in the CASTLE substudy reported a greater loss of trunk mean percent BMD in patients on LPV/r compared with those on ATV/r. While no statistically significant difference was seen overall in total body mean percent change between groups, when stratified by sex, greater total body mean percent BMD loss was seen in men on LPV/r compared with men on ATV/r, while no significant difference was seen among women [41*]. Although the evidence regarding the effects of PIs on bone health in treatment experienced patients is less robust, the SPIRAL-LIP study found a 0.01 g/cm 2 increase in the femoral neck BMD of virologically suppressed patients switched from a PI/r-based regimen to a RAL-based regimen, with no statistically significant difference in the total body or total hip BMD [43].…”

Section: The Bone Effects Of the Hiv Protease Inhibitorsmentioning

confidence: 99%

The protease inhibitors and HIV-associated bone loss

Moran

Weitzmann

Ofotokun

2016

Current Opinion in HIV and AIDS

View full text Add to dashboard Cite

Purpose of review HIV infection is an established risk factor for osteoporosis and bone fracture. Combination antiretroviral therapy (cART) increases bone resorption leading to an additional 2–6% bone mineral density (BMD) loss within the first 1–2 years of therapy. While tenofovir disoproxil fumarate is often blamed for antiretroviral drug-associated bone loss, evidence abounds to suggest that other agents, including the protease inhibitors (PI) have adverse bone effects. In the current review, we examine bone loss associated with PI use, describing the relative magnitude of bone loss reported for individual PIs. We also review the potential mechanisms associated with PI-induced bone loss. Recent findings As a class, PIs contribute to a greater degree of bone loss than other anchor drugs. HIV disease reversal and the associated immune reconstitution following cART initiation play an important role in PI-mediated bone loss in addition to plausible direct effects of PIs on bone cells. Summary PIs remain an important component of cART despite their adverse effects on bone. A better understanding of factors that drive HIV/cART-induced bone loss is needed to stem the rising rate of fracture in the HIV-infected population.

show abstract

Section: The Bone Effects Of the Hiv Protease Inhibitorsmentioning

confidence: 99%

The protease inhibitors and HIV-associated bone loss

Moran

Weitzmann

Ofotokun

2016

Current Opinion in HIV and AIDS

View full text Add to dashboard Cite

show abstract

“…In multivariate analysis, the loss of BMD at 96 weeks in patients treated with lopinavir/ritonavir was greater (by 2% in trunk and 1.3% in total body) than the loss observed in atazanavir/ritonavir‐treated patients. These investigators also observed a faster decline in BMD among older aged patients on these PI‐based regimens, with a 0.2% loss of total body BMD for every additional year of age . TDF in particular has been independently associated with a significant decrease in BMD at the hip (OR 2.8, 95% CI 1.3–5.9) and at the lumbar spine (OR 2.4, 95% CI 1.2–4.9) …”

Section: Toxicitymentioning

confidence: 82%

“…Mean BMD changes in the spine were −3.8% versus −1.8%, respectively (p<0.001), and changes in the hip were −3.7% versus −2.4%, respectively (p=0.005) . Another group compared BMD changes from baseline to week 96 of treatment with a combination of TDF/emtricitabine plus either atazanavir/ritonavir or lopinavir/ritonavir. In multivariate analysis, the loss of BMD at 96 weeks in patients treated with lopinavir/ritonavir was greater (by 2% in trunk and 1.3% in total body) than the loss observed in atazanavir/ritonavir‐treated patients.…”

Section: Toxicitymentioning

confidence: 99%

Antiretroviral Treatment Efficacy and Safety in Older HIV‐Infected Adults

2015

View full text Add to dashboard Cite

Highly active antiretroviral therapy (ART) and its widespread availability have revolutionized the landscape of HIV care and patient outcomes, transforming infection with HIV into a manageable chronic condition rather than a life-limiting disease. This transformation has created an older patient demographic. The effect that older age has on the outcomes of ART is not completely understood. Limited data are available in older individuals due to underrepresentation in clinical trials. To better understand this relationship, we conducted a literature search to assess the impact of older age on the outcomes of ART in the older HIV-infected population, including immunologic and virologic outcomes, mortality, disease progression, toxicity of ART, and pharmacokinetic considerations. In addition, package inserts of antiretroviral (ARV) medications were reviewed for efficacy, safety, and pharmacokinetic information pertaining to the older population. Most studies in older adults (50 yrs or older) demonstrated slower and blunted CD4 immune recovery but better virologic suppression in response to ART. Higher rates of mortality and faster disease progression have been observed in adults 50 years and older, particularly during the first year after ART initiation. HIV-infected patients aged 50 years and older appear to be at greater risk for certain ART-associated toxicities including nephrotoxicity, decline in bone mineral density and bone fracture, symptomatic peripheral neuropathy, and cardiovascular disease including myocardial infarction. The available literature suggests that clinicians should consider avoiding agents such as tenofovir disoproxil fumarate (TDF) in older patients with risk factors for renal impairment and/or osteoporosis. If TDF is used in patients aged 50 years or older, more frequent monitoring should be considered. Older age was a significant predictor for higher atazanavir exposure and higher lopinavir trough concentration at 24 weeks. The clinical implications of these findings are unknown. It is imperative that future development of novel ARV drug therapies includes a greater proportion of older subjects in clinical trials.

show abstract

“…Low nadir CD4 cell counts have been associated with larger declines in BMD [62]. It is probable that HIV-related immune activation may also be a causative factor, with cytokines such as OPG and RANKL (associated with osteoclast activation and bone resorption) being present at higher concentrations in untreated HIV-infected patients compared to those with treated HIV or non-HIV-infected controls [63].…”

Section: Tolerability and Toxicitymentioning

confidence: 99%

Tenofovir: What We Have Learnt After 7.5 Million Person-Years of Use

Ustianowski

Arends

2015

Infect Dis Ther

View full text Add to dashboard Cite

Tenofovir was licensed for use in patients with HIV in 2001 and since then has become a firmly established anti-retroviral in both guidelines and routine practice. Data have been presented from many pivotal studies—informing on its efficacy, use, and adverse features—and there are also over 7.5 million patient-years of experience to date. We explore the data on this nucleotide reverse transcriptase inhibitor in HIV presented since 2008—focusing on efficacy, side effects, and utility.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-015-0070-1) contains supplementary material, which is available to authorized users.

show abstract

Changes in Bone Mineral Density After 96 Weeks of Treatment With Atazanavir/Ritonavir or Lopinavir/Ritonavir Plus Tenofovir DF/Emtricitabine in Treatment-Naive Patients With HIV-1 Infection

Cited by 10 publications

References 35 publications

The protease inhibitors and HIV-associated bone loss

The protease inhibitors and HIV-associated bone loss

Antiretroviral Treatment Efficacy and Safety in Older HIV‐Infected Adults

Tenofovir: What We Have Learnt After 7.5 Million Person-Years of Use

Contact Info

Product

Resources

About