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Low CD4 Count at Start of HIV Treatment Linked to Greater Bone Loss


People who had low CD4 T-cell counts when they started antiretroviral therapy (ART) were significantly more likely to experience bone loss after ART initiation, especially if they also had high viral load, researchers reported in the August 13, 2013, advance edition of Clinical Infectious Diseases.

Many researchers have reported low bone mineral density (BMD) in people with HIV, but it is not yet clear whether this is due to HIV infection itself, resulting inflammatory or metabolic changes, immune reconstitution, antiretroviral drug toxicities, or a combination of these and possibly other factors. Studies generally see a BMD decrease of about 2%-6% during the first months or years on ART, which then levels off. The link between bone loss and fractures in this population is also not well understood.

Philip Grant fromStanford University and colleagues analyzed bone loss among participants in 3 trials of treatment-naive people with HIV, looking at the influence of pre-treatment immune deficiency, immune recovery on ART, hepatitis C virus (HCV) coinfection, exposure to specific antiretrovirals including protease inhibitors and tenofovir (Viread, also in several coformulations), and a variety of other factors.

The analysis included a total of 796 patients starting ART for the first time between 1998 and 2007. Most (83%) were men, a majority were white, and the median age was 39 years. At baseline they had relatively advanced HIV disease, with a median CD4 count of 208 cells/mm3 and a median viral load of 63,000 copies/mL. About two-thirds started a protease inhibitor-based regimen and about one-quarter included tenofovir.

Participants underwent whole-body dual-energy X-ray absorptiometry (DEXA) scans to assess bone density at baseline and at 96 weeks after ART initiation. The researchers evaluated correlations between baseline CD4 count, absolute and relative CD4 cell changes after 16 weeks on ART, and BMD changes over 96 weeks.


  • The overall mean bone mineral density loss was 2% after 96 weeks on ART.
  • Baseline CD4 count was significantly associated with 96-week bone density loss in a multivariate analysis.
  • Participants with baseline CD4 counts <50 cells/mm3 had significantly greater bone loss -- 3% more -- than people with >500 cells/ mm3.
  • A greater relative increase in CD4 cells at week 16 was significantly associated with a greater decrease in BMD, but this was not the case for absolute CD4 cell gains.
  • The association between relative CD4 cell increases and greater bone loss no longer held, however, after controlling for baseline CD4 count.
  • Other factors independently associated with greater bone loss in a multivariate analysis included older age, female sex, lower body mass index, higher HIV viral load, and use of protease inhibitors or tenofovir.
  • The effects of CD4 count and viral load interacted, such that lower CD4 counts had a greater negative effect on bone density among people with higher HIV RNA levels.

"Low pre-treatment CD4+ count, but not greater CD4+ count increase, is a strong and independent risk factor for bone loss after ART initiation," the study authors concluded. 

"The underlying reason for the relationship between low baseline CD4+ count and bone loss with ART initiation is not known but suggests a potential role for the immune system in skeletal maintenance," they added.

"ART initiation at higher CD4+ counts may reduce the burden of osteoporosis and fragility fractures," they advised.



PM Grant, D Kitch, GA McComsey, et al. Low Baseline CD4+ Count is Associated with Greater Bone Mineral Density Loss after ART Initiation. Clinical Infectious Diseases. August 13, 2013 (Epub ahead of print).