Bone mineral density in HIV participants randomized to raltegravir and lopinavir/ritonavir compared with standard second line therapy.
OBJECTIVE
To compare changes over 48 weeks in bone mineral density (BMD) between participants randomized to lopinavir/ritonavir (LPV/r) + raltegravir (RAL) or LPV/r + 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second line therapy.


METHODS
48-week open-label sub-study of the Second Line trial conducted in South Africa, India, Thailand, Malaysia and Argentina.


METHODS
Dual energy X-ray absorptiometry scans of proximal femur and lumbar spine were performed at baseline and week 48. Linear regression was used to compare means of differences between arms. McNemars test compared osteopenia and osteoporosis. Associations between percentage BMD changes and baseline variables were assessed by multivariate linear regression.


RESULTS
Two hundred and ten participants were randomized. Analyses were adjusted for sex, BMI and smoking status. Mean (95% CI) proximal femur BMD% reduced over 48 weeks by -5.2% (-6.7 to -3.8%) in the LPV/r+2-3N(t)RTIs arm and by -2.9% (-4.3 to -1.5%) in the LPV/r+RAL arm (P = 0.0001). Lumbar spine BMD reduced by -4.2% (-5.7 to -2.7%) in the LPV/r+2-3N(t)RTIs arm and by -2.0% (-3.5 to -0.6%) in the LPV/r+RAL arm (P = 0.0006). The incidence of osteopenia (7.6%) and osteoporosis (2.0%) assessed over 48 weeks were similar between arms. Reduced BMD over 48 weeks was significantly associated with longer duration of tenofovir on study [% change (SE) -1.58 (0.38) femur, -1.65 (0.38) spine, P = 0.0001] and low baseline BMI [% change (SE) 0.5 (0.13) femur, 0.17 (0.07) spine; P < 0.01].


CONCLUSIONS
An N(t)RTI-sparing antiretroviral regimen of LPV/r and raltegravir as second line therapy is associated with less bone loss than a LPV/r regimen containing N(t)RTIs.
aThe Kirby Institute, University of New South Wales, Sydney, Australia bUCD School of Medicine and Medical Science, Dublin, Ireland cThe Alfred Hospital, Melbourne, Australia dCICAL, Buenos Aires, Argentina eThai Red Cross AIDS Research Center, Bangkok, Thailand fHopital Saint-Louis, Paris, France.
Allison
A
Martin
Cecilia
C
Moore
Patrick W G
PW
Mallon
Jennifer
J
Hoy
Sean
S
Emery
Waldo
W
Belloso
Praphan
P
Phanuphak
Samuel
S
Ferret
David A
DA
Cooper
Mark A
MA
Boyd
D015502:Absorptiometry, Photon; D000328:Adult; D001118:Argentina / Q000453:epidemiology; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000150:complications / Q000453:epidemiology*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007194:India / Q000453:epidemiology; D061466:Lopinavir / Q000009:adverse effects; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D010024:Osteoporosis / Q000150:complications / Q000453:epidemiology*; D015995:Prevalence; D011760:Pyrrolidinones / Q000009:adverse effects; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors; D019438:Ritonavir / Q000009:adverse effects; D013019:South Africa / Q000453:epidemiology; D013785:Thailand / Q000453:epidemiology; D016896:Treatment Outcome
D017320:HIV Protease Inhibitors; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D000068898:Raltegravir Potassium; D019438:Ritonavir