A two-drug antiretroviral
combination comprising raltegravir and ritonavir-boosted lopinavir has only a
modest impact on bone mineral density, a study presented to the International
AIDS Society conference (IAS 2011) in Rome shows.
The raltegravir (Isentress) and lopinavir/ritonavir (Kaletra) combination had the same
potency as a more traditional antiretroviral regimen – FTC/tenofovir (Truvada) and Kaletra. However, the tenofovir-containing regimen was associated
with decreases in both total bone density and density of bone in the lower
“Over 96 weeks of
therapy, total bone density decreased to a greater extent in the tenofovir/FTC
plus lopinavir/ritonavir group than in the raltegravir plus lopinavir/ritonavir
group,” comment the investigators.
It is now well
recognised that reduced bone density is a complication of HIV infection. Bone loss has been associated with duration of HIV infection, and with immune reconstitution on treatment, and treatment with specific anti-HIV
drugs may also affect the bone metabolism.
Tenofovir – a widely
used drug in first-line antiretroviral therapy – has been especially associated
with a reduction in bone density.
There is a fear that
long-term disturbances in bone metabolism could increase the risk of fractures
for an ageing HIV population, and the comparison of regimens with and without tenofovir is beginning to shed more light on extent to which tenofovir might affect bone mineral density, and in what circumstances.
Investigators from the
PROGRESS study therefore compared changes in bone mineral density after two years of HIV treatment in
patients treated with the integrase inhibitor raltegravir to those seen in
individuals taking Truvada-based
Reductions in bone
mineral density have been seen in patients treated with Kaletra, but the impact of raltegravir therapy on the bones is
Bone mineral density
was assessed using DEXA scans at baseline and again after 96 weeks.
A total of 205
patients were randomised in the open-label study. Approximately 75% were men,
19% were black and the average age was 40 years. All were starting HIV therapy for the first time.
associated with lower bone mineral density were black race (p = 0.004), a viral
load over 100,000 copies/ml (p = 0.006), a lower body mass index (p <
0.001), and lower levels of limb fat (p = 0.026).
After 48 and 96 weeks
of treatment similar proportions of patients in both treatment arms had an
undetectable viral load, and gains in CD4 cell count were also comparable
between the two regimens.
After 96 weeks of
therapy, total bone mineral density was essentially unchanged from baseline
among the raltegravir-treated patients.
However, there was a
reduction of approximately 2% among the patients taking tenofovir, a
significant difference (p < 0. 05).
In addition, only
modest reductions in bone density in the spine were recorded among the
raltegravir-treated patients, but a reduction of approximately 5% was observed
in those taking tenofovir (p < 0.05).
A 5% loss in bone
density at week 96 was seen in fewer than 5% of patients taking raltegravir,
compared to approximately 20% of individuals in the tenofovir arm (p = 0.003).
believe that this finding could be of clinical significance, noting “the
decreases observed in the lopinavir/ritonavir plus tenofovir/FTC group are
similar in magnitude to the bone mineral density losses observed during the
first two years of menopause”.
confirmed that patients taking raltegravir were less likely to experience loss
of total bone density than individuals treated with tenofovir (odds ratio [OR]
= 0.14; 95% CI, 0.04-0.55, p = 0.005).
associated the preservation of bone density during the two years of the study
included younger age (under 40 vs over 40, p = 0.018), a higher CD4 cell count
(over 200 vs under 200 cells/mm3, p = 0.011), and higher body mass
index (p =0.02).
“The minimal effect of
raltegravir, in combination with lopinavir/ritonavir, on bone mineral density
with antiretroviral initiation warrants confirmation through further study,”
the researchers conclude.