Bone Mineral Density in HIV-Negative Men Participating in a Tenofovir Pre-Exposure Prophylaxis Randomized Clinical Trial in San Francisco

San Francisco Department of Public Health, San Francisco, California, United States of America.
PLoS ONE (Impact Factor: 3.23). 08/2011; 6(8):e23688. DOI: 10.1371/journal.pone.0023688
Source: PubMed

ABSTRACT Pre-exposure prophylaxis (PrEP) trials are evaluating regimens containing tenofovir-disoproxil fumarate (TDF) for HIV prevention. We determined the baseline prevalence of low bone mineral density (BMD) and the effect of TDF on BMD in men who have sex with men (MSM) in a PrEP trial in San Francisco.
We evaluated 1) the prevalence of low BMD using Dual Energy X-ray Absorptiometry (DEXA) in a baseline cohort of 210 HIV-uninfected MSM who screened for a randomized clinical trial of daily TDF vs. placebo, and 2) the effects of TDF on BMD in a longitudinal cohort of 184 enrolled men. Half began study drug after a 9-month delay to evaluate changes in risk behavior associated with pill-use. At baseline, 20 participants (10%) had low BMD (Z score≤-2.0 at the L2-L4 spine, total hip, or femoral neck). Low BMD was associated with amphetamine (OR = 5.86, 95% CI 1.70-20.20) and inhalant (OR = 4.57, 95% CI 1.32-15.81) use; men taking multivitamins, calcium, or vitamin D were less likely to have low BMD at baseline (OR = 0.26, 95% CI 0.10-0.71). In the longitudinal analysis, there was a 1.1% net decrease in mean BMD in the TDF vs. the pre-treatment/placebo group at the femoral neck (95% CI 0.4-1.9%), 0.8% net decline at the total hip (95% CI 0.3-1.3%), and 0.7% at the L2-L4 spine (95% CI -0.1-1.5%). At 24 months, 13% vs. 6% of participants experienced >5% BMD loss at the femoral neck in the TDF vs. placebo groups (p = 0.13).
Ten percent of HIV-negative MSM had low BMD at baseline. TDF use resulted in a small but statistically significant decline in BMD at the total hip and femoral neck. Larger studies with longer follow-up are needed to determine the trajectory of BMD changes and any association with clinical fractures. NCT00131677.

Download full-text


Available from: Kenneth Mayer, Sep 27, 2015
23 Reads
  • Source
    • "In any case, only people with normal creatinine clearance should receive TDF, and both glomerular and tubular functions need to be monitored regularly during TDF treatment. Similarly, small reductions in bone-mineral density have been reported in healthy participants of PrEP trials receiving a TDF-containing PrEP regimen, but the clinical relevance of this currently remains unknown [19]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Following US Food and Drugs Administration approval in July 2012 of daily oral tenofovir and emtricitabine for pre-exposure prophylaxis (PrEP) to prevent HIV infection in high-risk individuals in the USA, there has been much controversy about the implementation of this PrEP regimen in other countries throughout the world, and in Europe in particular. In this review, we focus on the challenges and opportunities of a daily oral PrEP regimen to curb the rising incidence of HIV infection in high-risk groups, and particularly in men who have sex with men. A number of issues would need to be addressed before PrEP could be implemented, including assessing the real effectiveness and cost-effectiveness of daily PrEP, the sustainability of daily adherence, the risk of selecting resistance, the long-term safety, and the risk of change in sexual behavior that might offset the benefit of PrEP. Alternatives to a daily oral PrEP regimen are being explored.
    BMC Medicine 08/2013; 11(1):186. DOI:10.1186/1741-7015-11-186 · 7.25 Impact Factor
  • Source
    • "Topical and oral ART as pre-exposure prophylaxis has proven to be a highly ef fi cacious strategy to prevent HIV transmission (Grant et al. 2010 ; Abdool Karim et al. 2010 ) , but this approach has had various limitations. Some of these studies were stopped prematurely due to futility (van der Straten et al. 2012 ) and others have raised concerns about systemic toxicity like bone loss with oral tenofovir use (Liu et al. 2011 ) . Strategies that employ daily oral ART pre-exposure prophylaxis also may not be cost-effective (Keller and Smith 2011 ) . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Plasmacytoid dendritic cells (pDCs) are innate immune cells that are specialized to produce interferon-alpha (IFNα) and participate in activating adaptive immune responses. Although IFNα inhibits HIV-1 (HIV) replication in vitro, pDCs may act as inflammatory and immunosuppressive dendritic cells (DCs) rather than classical antigen-presenting cells during chronic HIV infection in vivo, contributing more to HIV pathogenesis than to protection. Improved understanding of HIV-pDC interactions may yield potential new avenues of discovery to prevent HIV transmission, to blunt chronic immune activation and exhaustion, and to enhance beneficial adaptive immune responses. In this chapter we discuss pDC biology, including pDC development from progenitors, trafficking and localization of pDCs in the body, and signaling pathways involved in pDC activation. We focus on the role of pDCs in HIV transmission, chronic disease progression and immune activation, and immunosuppression through regulatory T cell development. Lastly, we discuss potential future directions for the field which are needed to strengthen our current understanding of the role of pDCs in HIV transmission and pathogenesis.
    Advances in Experimental Medicine and Biology 01/2013; 762:71-107. DOI:10.1007/978-1-4614-4433-6_3 · 1.96 Impact Factor
  • Source
    • "We did not find a significant correlation between tenofovir exposure > 1 year and BMD in HIV-subjects, unlike previous reports [39,40]. Recent data showed that the introduction of tenofovir or emtricitabine/tenofovir was associated with a 0.8 %–1.1 % decrease in BMD which occurred mainly within the first year in high-risk HIV-infected individuals [41]. In our study the small number of enrolled HIV subjects and the long exposure to different antiretroviral drugs made it difficult to show the real impact of tenofovir exposure on BMD health. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite the reported high prevalence of osteoporosis in the human immunodeficiency virus (HIV)-population, there have been no previous studies examining dairy calcium intake and bone mineral density (BMD) in HIV-subjects.We assessed the prevalence of low BMD in HIV-infected and uninfected subjects and analyzed the effects of calcium intake, lifestyle and HIV-related risk factors on BMD. One hundred and twelve HIV-infected subjects were consecutively enrolled. Seventy- six HIV-uninfected subjects matched for age and sex were enrolled as the control group. The HIV-subjects were interviewed about lifestyle habits and completed a weekly food-frequency questionnaire to estimate calcium intake. HIV-RNA, CD4+ T-cell count and data on antiretroviral therapy were also recorded. Both biochemical bone turnover markers and BMD, assessed by dual-energy radiographic absorptiometry (DXA) were recorded in the HIV-cases and controls. We also calculated the 10-year fracture risks using the WHO FRAX equation. Osteoporosis prevalence was significantly higher in the HIV-cases than controls (p < 0.05). BMI values were positively correlated with BMD (p < 0.05). Vitamin D levels were lower in the HIV-subjects (p < 0.02). No correlation was found with daily calcium intake.BMI values were significantly correlated with dairy intake quartiles (p < 0.003). In HIV-subjects, the mean of FRAX score was 1.2 % for hip and 4.7 % for major osteoporotic fractures. On multivariate analysis of the lumbar spine DXA T-score, age (p < 0.005) and HIV/hepatitis C virus co-infection (p < 0.0001) were negatively correlated with BMD, while yogurt intake was a protective predictor of BMD (p < 0.05). In the femur DXA T-score, age (p < 0.01), nadir CD4 + T-cell count < 200 cells/μL (p < 0.05) and drug addiction ( p < 0.0001) were negatively correlated with BMD. Among the foods rich in calcium, yogurt was a protective predictor of BMD in HIV-subjects. HIV/HCV co-infection, nadir CD4 + T-cell count < 200 cells/μL and drug addiction were independent predictors of severe BMD. Promoting behavioral changes in food intake and lifestyle, aimed at the primary prevention of bone disease in the chronically-infected subjects seems to be essential for implementing medical intervention in these cases.
    BMC Infectious Diseases 08/2012; 12(1):192. DOI:10.1186/1471-2334-12-192 · 2.61 Impact Factor
Show more