People with HIV experience less bone loss if
they switch to a NRTI-sparing second-line regimen containing raltegravir,
researchers reported last week at the 7th International AIDS Society Conference on HIV
Pathogenesis, Treatment and Prevention in Kuala Lumpur. Other studies showed
that HIV infection is associated with increased risk of hip fractures and shed
light on different mechanisms of bone loss associated with HIV and hepatitis C.
studies have reported a link between HIV and reduced bone mineral density (BMD), including osteopenia and the more severe
osteoporosis. It is not yet clear whether this is
attributable due to HIV infection itself, resulting inflammatory and metabolic
changes, antiretroviral toxicity or some combination of factors.
studies have looked at bone changes after starting initial antiretroviral
therapy (ART) or switching drugs while on suppressive treatment, what happens
after switching from a failing regimen to second-line therapy is less well
In general, initial
ART studies typically show early bone loss soon after starting therapy, which stabilises
after a few months. Bone loss has been linked to use of NRTIs – especially tenofovir (Viread, also in
single-tablet regimens) – and protease
inhibitors; the effect of integrase inhibitors on bone density is not well characterised.
from the Alfred Hospital in Melbourne and colleagues looked at changes in bone
density among a subset of participants in the SECOND-LINE trial who switched
regimens due to virological failure of their initial non-nucleoside reverse
transcriptase inhibitor (NNRTI) combination.
Conducted in 37
countries across the globe, SECOND-LINE compared the safety and efficacy of a
World Health Organization-recommended second-line regimen – lopinavir/ritonavir
(Kaletra or Aluvia) plus two or three nucleoside/nucleotide reverse
transcriptase inhibitors (NRTIs) – versus a NRTI-sparing regimen of lopinavir/ritonavir
plus the integrase inhibitor raltegravir (Isentress).
The bone sub-study
included 210 participants at eight sites in five middle-income countries (Argentina, India, Malaysia, South
Africa and Thailand) that had capacity to do dual energy X-ray absorptiometry (DEXA) scans. DEXA was performed at baseline and at week
48, measuring BMD at the proximal femur and the lumbar spine.
Men and women were
equally represented, though there were more men in the NRTI-containing arm. The
mean age was 38 years and very few of the women were menopausal. Participants
were mostly Asian (51%) or African (43%). Hoy noted that this differs from most
ART bone studies to date, which have looked largely at white men.
been on their NNRTI-based first-line regimen for approximately three years on
average; prior use of protease or integrase inhibitors was excluded. Half had
used d4t (stavudine, Zerit), a
third had used AZT (zidovudine, Retrovir)
and 17% had used tenofovir. The median CD4 count was low, around 200 cells/mm3.
Most people saw their viral load re-suppressed after they started their study
Two thirds of study
participants had a body mass index (BMI) below 20 kg/m2 (with 18.5
the threshold for being considered underweight). While 17% were current
smokers, two-thirds were past smokers. About 30% had spine osteopenia and 20%
had femur osteopenia already at baseline.
people randomised to the raltegravir-containing regimen saw less decline in
bone density. BMD decreases at 48 week were significantly smaller in the
raltegravir group compared with the NRTI group both at the femur (-2.9 vs -5.2%,
respectively) and at the spine (-2.0 vs -4.2%). This finding was mirrored by
significant differences in T-scores and Z-scores, two standardised comparative measures of bone
likelihood of developing osteopenia or osteoporosis was similar between the two
groups. Among raltegravir recipients, the incidence of osteopenia was 7.6% at both
the femur and spine, compared with 7.5 and 8.6%, respectively, among NRTI
recipients. Corresponding osteoporosis rates were 1.0% at the femur and 3.8% at
the spine for raltegravir recipients compared with 3.2 and 5.4%, respectively,
for NRTI recipients.
In a multivariate
analysis, factors significantly associated with femur bone loss included longer
duration of tenofovir use during the study, lower baseline BMI, lower nadir
(lowest-ever) CD4 cell count and vigorous physical
activity. For spine bone loss, the significant predictors were tenofovir use during the study,
tenofovir use prior to the study, lower BMI and not being Asian.
The magnitude of bone loss seen in this first
study looking at ART-experienced patients with virological failure on a
first-line regimen was "similar to that observed in ART-naive patients
initiating therapy", the researchers concluded.
"The loss of BMD was least in participants
treated with raltegravir and greater in those exposed to tenofovir throughout
the study," they continued. "These data confirm that reduction in BMD
secondary to ART remains a significant co-morbidity in the long-term management