The push for drug holidays among people with HIV
experiencing long-term side-effects of anti-HIV therapy suggests that some
people may have begun treatment too early, according to leading HIV physician
and researcher, Professor David Cooper.
Speaking at a community forum on body fat changes and
metabolic disorders known as lipodystrophy at St Vincent’s Hospital, Sydney,
Professor Cooper said, "I often wonder if the people who are taking drug
holidays are the people who shouldn’t have been on the drugs in the first
place."
He said that people who had severe immune damage
before starting therapy should not be taking drug holidays. But they might be
persuaded to do so, Professor Cooper said, because people who treated early are
rethinking the costs and benefits of their treatment. While he acknowledged that
the early treatment group may benefit from ceasing treatments, Professor Cooper
said that this move may be dangerous for others with more advanced HIV
disease.
Treatment conservatism vindicated
The experience of lipodystrophy suggests the value of
a cautious approach to new treatments, according to Professor Cooper. Such
treatment conservatism was demonstrated in the UK. "There’s a much lower uptake
in the UK of aggressive treatment compared to the US. But the death rate in the
UK plummeted. The reason that it plummeted was because the people who were at
greatest risk of getting sick and dying went on treatment because it worked. So
I think that sometimes more conservative approaches are probably better and
reduce the possibility of long-term toxicities."
Over 50 people, many with clear physical signs of
lipodystrophy, most noticeably sunken cheeks, attended the forum. Many were
involved in St Vincent’s’ ground-breaking study of lipodystrophy.
Treatments spokesperson for the Australian National
Association for people with HIV/AIDS, Peter Canavan, described lipodystrophy as
a syndrome which once again marked bodies as HIV-infected. He said that this has
had a dramatic impact on the social and sexual lives of people living with
HIV.
It’s the drugs, stupid
St Vincent’s researchers believe that lipodystrophy
and metabolic disorders seen among people with HIV are due to antiretroviral
therapy. They argue that cases of this syndrome among uninfected people treated
with post-exposure prophylaxis and infected people treated during seroconversion
rule out the possibility that HIV is causing the syndrome.
However, the St Vincent’s team does acknowledge that
the nucleoside analogues as well as protease inhibitors are associated with the
syndrome. "I don’t think we have seen anyone who has classic lipodystrophy with
HIV who has never been treated", Professor Cooper said. "We have certainly seen
people who are on nucleosides only – AZT, d4T, ddI - with lipodystrophy but the
rate at which that’s happened is far lower than in people who are on nucleosides
and proteases."
Professor Cooper said that a number of studies now
link d4T and AZT to body fat changes. But St Vincent’s is not planning a study
in which people switch from these two drugs because the data is preliminary.
Furthermore, Professor Cooper said that d4T and AZT are both powerful drugs and
a switch may leave people vulnerable to viral rebound.
Nevertheless, for people with lipodystrophy who are
not taking protease inhibitors, the drug dilemma is difficult. "You’ve got to
substitute another drug and you don’t know that that (new drug) is not going to
be worse," Professor Cooper said.
Anecdotal reports of improvements in body fat and
metabolic disorders have led to the hope that switching drugs may reverse the
syndrome, although this is not yet proven. The St Vincent’s team has collected
six-month data on 80 people with lipodystrophy who were randomised to either
continue PI therapy, or switch to a non-PI regimen. Analysis of the data is now
underway and results are expected in a few months.