Introduction: Response to Kaletra (LVP/r) based salvage regimens may be influenced by both the number of mutations at the protease and LPV plasma levels. Moreover, cholesterol (CHOL) and triglyceride (TG) levels may be related to LPV levels.

Methods: All HIV⁺ patients (pts) with prior exposure to antiretrovirals from all three drug families and failing their current treatment were recruited in a multi-center trial in Spain. All subjects started a salvage regimen based on LPV/r at standard doses. Genetic sequences were obtained at baseline (BL). Interpretation of drug resistance was performed according to the latest IAS-USA guidelines. LPV minimum concentrations (Cmin) were measured at 3 months (mos). Viral load, CD4⁺ counts, fasting CHOL and TG levels were measured at BL and at 3 mos. Virological response was defined as > 1 log reduction in plasma HIV-RNA and/or to < 50 copies/ml.

Results: A total of 126 pts were analysed: 86 (68%) were virological responders (R) and 40 (32%) were non-responders (NR). At BL, the median number of mutations related to LPV resistance was 3 (0–10): 3.2 (0–9) in R versus 5 (1–10) in NR (p = 0.017). The mean LPV Cmin was 5.95 ug/ml (0–17.7): 6.64 in R versus 4.3 in NR (p = 0.008). In the multi-variate analysis, both LPV Cmin > 4.8 ug/ml and £ 5 LPV resistance mutations were independent predictors of virological response (p = 0.02; OR 4.6; 95% CI: 1.2–19.9; and p = 0.01; OR 6.25; 95% CI: 1.53–25, respectively). On average, the CD4 count increased +47 cells/ul in respect to BL (p = 0.001). Interestingly, there was a significant greater increase in pts with LPV Cmin > 5.8 mg/ml (p = 0.01; OR 2.9, 95% CI: 1.2–6.8). TG levels significantly increased (+74 mg/dl; p = 0.005), whereas CHOL levels did not change. The median percentage of increase (%D) for TG levels was 25%. A positive correlation was found between %D in TG and LPV Cmin (r = 0.26, p = 0.01). Moreover, 66.6% of pts with an increase in TG levels > 25% had LPV Cmin > 6.4 ug/ml (OR 3.3; 95% CI: 1.3–8.1; p = 0.008). No association was found between CHOL and LPV levels.

Conclusions: The virological response to a salvage therapy based on LPV/r is independently predicted by BL HIV protease genotyping and LPV Cmin. LPV Cmin was also predictive of both a greater CD4⁺ T-cell recovery and TG elevations.