Abstract Body

Background: Antiretroviral therapy (ART) should optimally cause minimal harm. Preferred N(t)RTI-backbones are associated with toxicities with poorly understood long term consequences. In the SECOND-LINE study we demonstrated non-inferiority (margin=12%) of ritonavir-boosted lopinavir (r/LPV) plus raltegravir (RAL-arm) compared to r/LPV plus 2-3N(t)RTI regimen (N(t)RTI-arm) after virological failure of standard NNRTI+2N(t)RTI first-line ART. The RAL-arm was associated with significantly less bone mineral density (BMD) loss. We hypothesised that the RAL-arm would be associated with a greater degree of limb fat gain at 96 weeks.

Methods: We performed a DXA-substudy of SECOND-LINE at weeks 0, 48 and 96 at 8 sites in Argentina, India, Malaysia, South Africa and Thailand. Primary endpoint was the mean percent change from baseline in peripheral limb fat. Analysis was by intention to treat (ITT). We adjusted for baseline imbalances in sex, BMI and smoking. Multivariate linear regression was used to assess between-group differences and predictors of percent change in limb fat mass. Results are mean (SD) and median (IQR).

Results: Baseline characteristics of the 210 enrolled participants: 110 (52%) female, age 38.6 (7.8) years, 52% Asian/43% African, HIV RNA 4.1 (1.0) log10 copies/mL, CD4+ count 220 (167) cells/µL, first-line ART duration 3.3 (1.9-5.9) years, 34%% and 48% on d4T and AZT respectively prior to initiating randomised ART. Eighty six percent and 42% N(t)RTI arm study participants received TDF and AZT respectively. After 96 weeks the mean (SD)% limb fat change from baseline was 16.8 (32.6)% in the N(t)RTI-arm and 28.0 (37.6)% in the RAL-arm, a mean difference (95% CI) of 10.2 (0.1-20.4)% (p=0.048). Baseline predictors of percent changes in limb fat mass over 96 weeks are shown in Table 1.

Conclusions: Although N(t)RTI-sparing in SECOND-LINE was associated with improved peripheral limb fat gain over 96 weeks, it was not significant after adjustment for other predictors on multivariate analysis. Significant predictors of peripheral fat gain were female sex, higher baseline BMI and a greater increase in BMI. Africans were more likely to lose limb fat than Asians. Those with more limb fat at baseline were more likely to lose limb fat over 96 weeks. Thymidine-analogue duration prior to study had a borderline association with less peripheral fat gain.

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