People taking HIV
treatment based on ritonavir-boosted atazanavir and darunavir have comparable long-term
increases in lipid levels, investigators from the United States report in the
online edition of Clinical Infectious
Diseases. Trough concentrations of ritonavir were not associated with lipid
levels. This is an important finding.
The authors explain: “The lipid changes
experienced with ritonavir boosted PI [protease inhibitor] therapy are
speculated to be driven to a larger extent by the ritonavir component of the
regimens”. This could be because of the way ritonavir is processed by the body.
The present research provided an opportunity to test this theory, but showed
“associations between ritonavir exposure and lipid changes over 48 and 96
[weeks] were…not apparent (both overall and within specific PI regimens).”
antiretroviral therapy, many people with HIV now have a normal life expectancy.
However, several anti-HIV drugs, especially protease inhibitors, have been
associated with lipid disturbances. Given that cardiovascular disease is an
increasingly important cause of illness and death in people with HIV, it’s
important to identify which drugs carry the biggest risk of lipid
ACTG 5257 was an
open-label, phase III, randomised study comparing the safety and efficacy of
regimens based on ritonavir-boosted atazanavir, ritonavir-boosted darunavir or
the integrase inhibitor raltegravir. All the participants in the study were
antiretroviral naive at baseline (had not previously taken treatment when the
study started) and were also taking the fixed-dose combination emtricitabine/tenofovir
The study also gave investigators
the opportunity to compare long-term changes in lipid profiles, incidence of
metabolic syndrome and alterations in body shape according to regimen.
Additionally, for people taking the protease inhibitors, the investigators also
examined whether trough levels of ritonavir were correlated with lipid changes
and if these differed between regimens.
Approximately 1800 people
were recruited to the study between 2009 and 2011. A quarter were women, 34% were African American, 42% were white and 21%
A fifth of participants
had metabolic syndrome at baseline. Prevalence did not differ by regimen and
lipid profiles were also comparable between regimens.
During 96 weeks of follow-up,
lipid levels increased with all three regimens. However, these were milder with
raltegravir compared to the boosted protease inhibitors (p < 0.001).
Approximately a fifth
of participants in each study arm developed metabolic syndrome during
follow-up. At week 96, rates of use of lipid-lowering agents were also
comparable between the three study medications (9 to 14%). People taking
raltegravir experienced a larger increase in waist circumference compared to
those treated with ritonavir-darunavir but not ritonavir-atazanavir.
of ritonavir did not differ between arms, and there was no evidence of a
correlation between ritonavir levels and lipid profile.
the most favourable lipid profile compared with the two ritonavir boosted PIs,”
comment the authors.
They were concerned by
the high prevalence of metabolic syndrome at baseline and also the
approximately 20% incidence observed during follow-up.
clinical significance of the lipid changes noted with the two ritonavir boosted
PI regimens relative to the raltegravir based regimen deserve further
evaluation, particularly when initiating antiretroviral therapy in patients
with high cardiovascular risk profiles,” conclude the authors.