HIV-negative persons receiving Pre-Exposure Prophylaxis (PrEP)

 PrEP is recommended in HIV-negative persons who are at high-risk for HIV infection.¹³ The recommended regimen for PrEP involves a fixed-dose combination of oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). Given the association of TDF with bone loss, concern exists about bone toxicity in those receiving PrEP.  A sub-study from an earlier trial of PrEP conducted in San Francisco, showed a small but significant decrease in BMD from baseline, greater at the femoral neck.⁴⁰ These changes occurred in the first 12 months of tenofovir therapy with no further decline at 24 months. A similar decrease in BMD was seen in a pre-exposure prophylaxis study in Botswana, involving both men and women.⁴¹

 More recent data comes from a DXA sub-study of the Pre-exposure Prophylaxis Initiative (iPrEx), a large trial conducted using FTC/TDF.⁴² This study found that BMD decreased in those randomised to FTC/TDF in the spine and at the hip.  In the spine, the net difference was -0.91% and the net difference at the hip was -0.61%. Changes in BMD at week 24 correlated inversely with intracellular tenofovir diphosphate.  In this study, almost 50% of the study subjects were aged less than 25 years of age, making the study findings less applicable to older HIV-infected populations.  Further studies to examine the risk of bone loss in those receiving PrEP are required.  In the meantime, those commencing PrEP should be informed of this potential risk.

 Children and adolescents

 In this population, the impact of HIV and its therapy on developing bones may be different from adult populations.  The assessment of potential effects needs to be counterbalanced by the expected changes in bone throughout childhood and adolescence.⁴⁴ Most studies of perinatally infected children have shown lower than expected bone mass.⁶ The prevalence of low BMD may be lower in high-income settings than in middle-income settings, perhaps explained by lower nadir CD4+ T cell count, poorer nutritional status and more advanced HIV disease stage.⁴⁴

 Studies have reported variable effects of ART on bone density in this population.  Most data are provided by switch or salvage studies with little data available from treatment-naïve populations.  In children, tenofovir and boosted protease inhibitors are most often associated with low BMD. ^44,45 The impact of in utero exposure to antiretroviral agents is an area of ongoing investigation. Recent studies suggest that in utero exposure to TDF has minimal effect on infant bone mass.⁴⁵ Current WHO guidelines continue to support the use of TDF containing regimens in pregnancy.⁴⁶ Maintaining good bone health is essential in children.  This includes obtaining adequate nutrition and physical activity and avoiding cigarette smoking.⁴⁸