A low baseline CD4
cell count is associated with loss of bone mineral density (BMD) during the
early years of HIV therapy, US investigators report in the online edition of Clinical Infectious Diseases. Results of
three studies conducted between 1998 and 2007 were included in their analysis.
DEXA-scan monitoring showed that immune suppression before starting HIV therapy
was a risk factor for loss of BMD during treatment.
“We found a strong
and independent association between low baseline CD4+ count and total BMD loss
in the first two years of treatment,” write the authors. “We did not find any
evidence that the extent of immune reconstitution…was associated with BMD
change after controlling for baseline CD4+ count.” The investigators believe
their findings underline the importance of early HIV treatment.
HIV infection is
associated with loss of bone mineral density and an increased risk of
fractures. Loss of bone continues after HIV therapy is started, and decreases
in BMD of between 2 and 6% typically occur in the first two years of
The reasons for
this are not clear. To gain a better understanding of the causes,
investigators examined BMD in approximately 800 people who underwent whole
body DEXA scanning before starting HIV therapy and again after 96 weeks.
The participants in the study had a
median age of 39 years and 83% were male. Baseline BMI was 25 kg/m2. Median baseline CD4 cell count
and viral load were 208 cells/mm3 and 63,000 copies/ml,
respectively. Almost two-thirds of participants (62%) started HIV therapy with a
regimen based on a protease inhibitor and 27% received tenofovir (Viread, also in Truvada and Atripla).
These drugs have been associated with reduced BMD in other research.
The mean loss of
total BMD at week 96 was 2%. Baseline CD4 cell count was strongly associated
with BMD loss. Participants with a pre-therapy CD4 cell count of below 50 cells/mm3
lost 3% more BMD than people with a baseline CD4 cell count above 500
cells/mm3 (p < 0.001) and approximately 2% more BMD than people
with CD4 counts between 350 and 499 cells/mm3.
relative, but not absolute, CD4 cell count 16 weeks after starting therapy
was initially shown to increase BMD loss (-2.3% per tenfold increase, p <
0.001). However, this association disappeared after controlling for baseline
CD4 cell count.
After taking into
account confounding factors, a low baseline CD4 cell count remained strongly
associated with BMD loss at week 96. Individuals with a pre-therapy count below
50 cells/mm3 lost 2.27% more BMD at this follow-up point compared to
people with a baseline CD4 count above 500 cells/mm3 (p <
“We found that
even after controlling for multiple confounders such as BMI that there was a
robust relationship between low baseline CD4+ count and greater bone loss after
ART [antiretroviral therapy] initiation,” comment the authors. “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.”
Older age (each
additional year, p < 0.001), female sex (p = 0.007), low BMI (p < 0.001)
and a high HIV viral load (p = 0.002) were also associated with greater bone
initial regimen included tenofovir lost on average 1.38% more BMD at week 96 (p
< 0.001) compared to people taking an alternative drug. Individuals taking
a protease inhibitor lost approximately 1% more BMD at follow-up (p = 0.001)
compared to individuals taking an alternative class of drugs.
There was also a
significant interaction between lower CD4 cell count and higher viral load and
BMD loss (p = 0.043). In patients with a higher viral load, the negative effect
of a low CD4 cell count on BMD was greater than in individuals with a lower viral
note that the BMD changes found in their study were relatively “modest” and of
unknown clinical significance. They also emphasise that they did not have data
on some factors associated with bone loss such as tobacco and alcohol use,
testosterone and vitamin D levels, and use of medicines that can affect BMD.
authors conclude: “low pre-treatment CD4+ count, but not early CD4+ change with
ART was a strong and independent risk factor for bone loss after ART initiation,
providing further evidence for the benefits of early initiation of ART.”