Strong evidence that d4T (stavudine, Zerit)
contributes to the body fat changes seen frequently in people on anti-retroviral
treatment was presented at an international workshop on adverse drug effects in
HIV last week.
Five cohort studies from France, Italy, Australia and
the US found a significant association between d4T treatment and fat loss from
the face, arms, legs or buttocks. Two of these cohort studies, from the US and
Australia, found that the length of time on d4T increased the risk of fat loss.
The Australian report found that each year of d4T treatment increased the risk
of fat loss from the arms or legs by 256%.
However, one cohort study from France found no
association, and an analysis of a large trial of d4T/ddI similarly found no
association.
One study found that all nucleoside analogues were
implicated to some extent; two studies found that taking 3TC was also associated
with fat loss, and one study found that length of time on AZT was linked to risk
of fat loss.
The mechanism by which d4T or other nucleosides might
cause fat loss is unclear. One suggestion is that nucleoside analogues may
damage the DNA of adipocytes (fat cells) that store fat in the limbs. Until now
it had been thought that protease inhibitors might be responsible for the loss
of fat in people receiving HAART, but the First International Workshop on
Adverse Drug Reactions and Lipodystrophy in HIV Infection heard that this form
of fat loss is also being seen in some people who have never taken protease
inhibitors.
Another explanation offered is that the association
between d4T treatment and fat loss may be a surrogate marker for length of time
on successful therapy, or duration of HIV infection. One study found that people
with higher CD4 counts when starting therapy were at lower risk of experiencing
fat loss, but not every cohort study investigated these potential links. If this
were the case, it is not surprising that d4T is more strongly linked than AZT to
fat loss, because d4T is now more widely prescribed than AZT, and has been for
several years.
A detailed report on these findings, discussing the
data from each cohort, is available at href="http://www.hivandhepatitis.com/html/confrprt2.html">http://www.hivandhepatitis.com/html/confrprt2.html