Bone mineral density over 96 weeks in adults failing first-line therapy randomized to raltegravir/lopinavir/ritonavir compared with standard second-line therapy.

OBJECTIVE: To compare bone mineral density (BMD) changes over 96 weeks in adults virologically failing standard first-line therapy, randomized to raltegravir plus lopinavir/ritonavir (RAL + LPV/r) or conventional 2-3 nucleoside/nucleotide reverse transcriptase inhibitors [N(t)RTIs] + LPV/r second-line therapy. METHODS: Participants underwent dual-energy x-ray absorptiometry at baseline and weeks 48 and 96 to measure total hip and lumbar spine BMD. Analyses were adjusted for gender, body mass index, and smoking. Linear regression was used to compare between-group differences, logistic regression for low BMD (hip or spine Z-score ≤ -2) incidence, and multivariate linear regression to determine predictors of BMD change. This work represents the extension and final results of the previously published initial 48 weeks of the study. RESULTS: The population included 210 adults from 5 middle-income countries: 52% females, 52% Asians, 43% Africans, mean age, 39 years (SD, 8 years). In the 2-3 N(t)RTI group (vs. RAL), BMD reduction was greater at the spine (mean change, -4.9% vs. -3.5%; adjusted difference, -1.9%; 95% confidence interval: -3.3 to -0.5%, P = 0.009) and hip (-4.1% vs. -2.2%; -1.9%; -3.4 to -0.4; P = 0.012). BMD decrease was greatest at 48 weeks with stabilization to week 96. Overall, low BMD occurred in 15 participants (7.9%), with no between-group differences. Independent predictors for bone loss included lower body mass index (regression coefficient: hip, -0.18% and spine, -0.26% per 1 kg/m), longer tenofovir exposure (hip, -0.74% and spine, -1.0% per year), greater change in CD4 to week 12 (hip, -5.11% per 10-fold higher), and higher baseline HIV-RNA (spine, -0.7% per 10-fold higher). CONCLUSIONS: Over 96 weeks, there was greater BMD decrease with 2-3 N(t)RTI + LPV/r compared with RAL + LPV/r; the relative decrease at the spine was greater than the hip. BMD decreases with second-line antiretroviral therapy largely occurred in the first 48 weeks with stabilization, but no recovery thereafter.

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. DESIGN: 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]. CONCLUSION: 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.