between HIV therapy and fracture risk is far from straightforward, US research
presented to the International AIDS Society conference (IAS 2011) in Rome suggests.
An analysis including
over 56,000 HIV-positive military veterans who received care between 1988 and
2009 failed to find any significant association between antiretroviral
treatment and fragility fractures.
Incidence of fractures
increased after the introduction of effective HIV therapy, but the researchers
believe that this could simply be because more patients were surviving into
However, when analysis
was restricted to patients who received care after 1996, an association was
found with tenofovir (Viread, also in
the combination pills Truvada and Atripla) and lopinavir/ritonavir (Kaletra). Even so, the investigators
stress that traditional risk factors such as smoking and diabetes were much
It is now well known
that bone mineral density is reduced in patients with HIV. The exact causes are
controversial, but appear to include traditional risk factors, especially older
age, HIV infection, and possibly therapy with some antiretroviral drugs.
significance of this reduced bone mineral density is also unclear. Some (but
not all studies) have found that it is associated with an increased risk of
so-called fragility fractures (a fracture that occurs from a fall from standing height or less, usually to the wrist, vertebrae or hip).
Investigators from the US Department of Veterans’ Affairs conducted a
retrospective study involving patients who received care between 1988 and 2009.
Data were gathered on
the incidence of fragility fractures, and the patients’ medical records were
examined and information extracted on traditional, HIV-related, and
antiretroviral-related risk factors.
Incidence of fractures
increased from 1.61 events per 100 person-years in the pre-treatment era to
4.06 events per 100 person-years after the introduction of combination HIV
Fracture rates were
significantly higher among men, smokers, individuals with diabetes, and those
co-infected with hepatitis C virus (all p < 0.0001).
The first set of
statistical analysis showed a significant association between fragility
fractures and traditional risk factors including white race (p < 0.0001),
older age (p < 0.0001), smoking (p = 0.003), lower body mass index (p =
0.007), and hepatitis C co-infection (p < 0. 0001).
Cumulative exposure to
antiretroviral therapy was significant in univariate analysis (p = 0.02), but
fell just short of significance in the adjusted model (p = 0.77).
An analysis of the
entire cohort of patients found a significant association between fragility
fracture risk and tenofovir therapy (p < 0.001), as well as treatment with Kaletra (p = 0.015). However, both
associations ceased to be significant after controlling for traditional risk
The investigators then
restricted their analysis to people who received care after 1996, following the
introduction of effective combination HIV treatment.
association was found with tenofovir therapy, even after controlling for
traditional risk factors, each year of treatment increasing the risk by
approximately 12% (hazard ratio [HR] = 1.12; 95% CI, 1.02-1.21, p = 0.011).
After controlling for
other risk factors, there was also a significant association with Kaletra, therapy with this drug
increasing the risk of fragility fractures by 8% (HR = 1.08; 95% CI, 1.01-1.15,
p = 0.026).
When the two drugs
were used together, the risk of fractures was further increased.
Despite these finding,
the investigators were circumspect about the association between antiretroviral
therapy and the risk of fractures.
Most importantly, the
risk associated with cumulative exposure to HIV therapy was modest when
compared to those associated with traditional risk factors, especially white
race, ageing and smoking.
They also suggest that
the higher fracture rates in the treatment era, and the significant association
with tenofovir and Kaletra, could
simply be because people with HIV are living longer.
Although they believe
that the large sample size was a major strength of their study, they also note
a number of limitations. These include the retrospective design, and the fact that no
information was available on the patients’ bone mineral density.
exposure likely does not account for the increased risk in the HAART era,”
conclude the investigators.