Treatment with the HIV integrase inhibitor
raltegravir (Isentress) is associated
with an increased risk of skeletomuscular side-effects, according to Australian
research published in the online edition of the Journal of Acquired Immune Deficiency Syndromes. Toxicities
included muscle pain and muscle weakness and wasting. However, in most instances,
these side-effects were mild and in the case of muscle wasting/weakness
disappeared with the cessation of raltegravir therapy.
“This study identifies a significantly
higher prevalence of symptomatic skeletal muscle toxicity…in patients treated
with raltegravir-based cART [combination antiretroviral therapy],” write the
authors. “This association is not dependent upon either the duration of
raltegravir exposure or raltegravir trough levels.”
Raltegravir is a potent antiretroviral drug
with proven efficacy in both treatment-naive and treatment-experienced
people. Its main side-effects are headache, diarrhoea and nausea. These are
generally mild and time limited.
Nevertheless, four case reports have
associated raltegravir with rhabdomyolysis – the breakdown of skeletal muscle
fibre. Elevations in creatinine kinase levels have also been observed in
people treated with raltegravir, a finding which is consistent with the
hypothesis that the drug may cause low-grade muscular toxicities.
To get a clearer understanding of this
question, doctors in Sydney designed a prospective study comparing the
prevalence and risk factors for skeletomuscular side-effects between people
taking HIV treatment based on raltegravir and individuals treated with
alternative antiretroviral regimens.
A total of 318 participants were recruited to
the study between 2011 and 2012. Half were treated with raltegravir.
Muscle toxicity was defined as any one of
- Isolated elevation in
- Widespread muscle pain (myalgia).
- Muscle weakness or wasting
There were no significant differences
between the participants treated with raltegravir and those taking other regimens.
Almost all (98%) were male, 89% were white and their median age was 51 years.
Strenuous exercise – which can cause
muscle soreness or weakness – was reported by 42% of participants.
The overall prevalence of muscle toxicity
was 28%. This was significantly higher among the participants taking
raltegravir-based treatment compared to individuals treated with alternative
regimens (37 vs 19%, p < 0.001).
Looking at individual muscle toxicities,
the investigators found that participants taking raltegravir were more likely to be
diagnosed with myalgia than those in the control arm (19 vs 3%, p <
0.001). “Myalgia, although a common clinical finding, is unlikely to be a
sufficient reason alone to switch from raltegravir, but cases should be
considered on an individual basis,” suggest the authors. Prevalence of proximal myopathy was also more
common in those taking raltegravir (4 vs 0%, p = 0.03).
Prevalence of isolated elevation in
creatinine kinase was similar between the two study arms (14 vs 16%). There
were no cases of rhabdomyolysis.
After controlling for potential
confounders, raltegravir (OR = 2.64; 95% CI, 1.57-4.45, p < 0.001) and
recent strenuous exercise (OR = 2.15; 95% CI, 1.35-3.75, p = 0.002) were both
identified as having an independent and significant association with muscle
In addition, myalgia was associated with
raltegravir treatment (p < 0.001) and strenuous exercise was a risk factor
for isolated elevation in creatinine kinase.
“Additional, prospective studies are
necessary to better assess the long-term sequelae of muscle toxicity and
uncover associated factors that may predict the likelihood of damage,” conclude
the authors. “Our findings suggest that all patients receiving raltegravir
should be actively monitored for myalgia and myopathy.”