|ART is a contributing factor to loss of bone density in people with HIV, |
but the reasons for it are not yet understood. Image: aidsinfo.nih.gov
Contemporary antiretroviral therapy (ART) has transformed the lives of people living with HIV (PLWH) dramatically, with life expectancy near normal and their quality of life improved.
However, it has been known for some time that people with HIV are at greater risk of loss of bone density and fractures, with ART a contributing factor. Professor Jenny Hoy, Professor Director of HIV Medicine at the Alfred Hospital and Monash University, recently conducted a review of all available randomised trial data in which fractures were measured to evaluate the problem.
The review, conducted with a US researcher, was published in ‘Current Opinion of HIV and AIDS’ last year in an edition devoted to issues associated with HIV and bone with input from all those working in the field.
It found that HIV infection is clearly associated with an increased risk of fracture compared with age-matched and sex-matched individuals, likely due to the increased prevalence of low bone mass.
Elevated rates of fracture were most pronounced in older people with HIV – those in their sixties, seventies and eighties. Understanding those at greatest risk will enable interventions to be put in place to prevent the fractures, the study said. The impact of a fracture can be serious; a major hip fracture for example, can mean a lower survival rate for an elderly person, and higher rates of hospitalisation and pneumonia.
The review found that an increased fracture rate was associated with traditional risk factors (low Body Mass Index, smoking and alcohol), HIV-related factors (low CD4+ cell count, immunodeficiency) and increased ART-related bone turnover. Faster bone turnover means the bone has less chance to build a matrix so it has defects that make it less strong and more prone to fractures, Professor Hoy said.
The overall benefits of ART however, including to cardiovascular disease, cancers and survival rates, outweighed the adverse effect of ART on bone health, she said. “Everything gets better except your bones.”
Professor Hoy’s team in Infectious Diseases has previously demonstrated that if you stopped using the particular type of ART that causes bone loss and replaced it with another drug, that bone loss can be regained. A recent study elsewhere suggested bone loss could also be mitigated with the addition of anti-osteoporosis drugs to the treatment regimen.
“But I’d like to understand why it happens,” Professor Hoy said. “We don’t know what it is in the drug that causes the bone loss.
“If we understood what turns the bone loss on and off then we could target that better, rather than using a global anti-osteoporosis drug. It would be better to find that cause and act on that.”
For Professor Hoy, who has been interested in the link between ART and bone loss since she first observed it in 2000, that is the ultimate challenge.
The START study (‘Strategic Timing of Antiretroviral Treatment’), a randomised, controlled clinical trial of 4,685 HIV-positive adults, recommended that people diagnosed with HIV infection should be offered ART immediately rather than when their CD4+ cell count reached a certain level, meaning that more people will be using ART for longer periods of time.
Professor Hoy and a colleague from Sydney were principal investigators on the START Bone Mineral Density substudy, which enrolled 424 people from the parent START study. This work was funded by two NIH grants with some contribution from an NHMRC grant.
The results of the study were presented at the European AIDS conference. People randomised to start ART immediately experienced a mean 2.2% loss of bone over 12 months compared with 0.3% in the deferred ART arm. This is the same amount of bone loss with low dose prednisolone and in older people means an increased risk of fracture.
Recent changes to global HIV treatment guidelines, based on the findings of a major international study, have made researching the effects of long-term ART on bone health even more important, Professor Hoy said. “We have no cure for HIV, so ART is life-long.”
Hoy J, Young B. Do people with HIV infection have a higher risk of fracture compared withthose without HIV infection? Curr Opin HIV AIDS. 2016 May;11(3):301-5. doi: 10.1097/COH.0000000000000249.