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Background: Lopinavir/ritonavir (LPV/r, Kaletra) has demonstrated a good antiviral activity in ARV-naïve and –experienced HIV-infected adults. The purpose of this study was to assess the virological and immunological outcome of the use of LPV/r in HIV-infected children.

Methods: We enrolled 69 PI-naive (n = 21) and PI-experienced (n = 48) children were enrolled in an observational cohort of LPV/r treatment. Viral load, %CD4, resistance genotype, LPV maximal drug level (Cmax) were measured at baseline and during LPV/r therapy. The virological response was defined as viral load <1000 copies/mL or -2 log viral load decrease after 6 months of LPV/r therapy and the virological failure, defined as 2 consecutive viral loads >1000 copies/mL, was studied during the long term LPV/r use (mean 15 months). The PI resistance mutations included in the LPV score were at codons 10, 20, 24, 33, 46, 50, 53, 54, 63, 71, 82, 84, 90 (French ANRS Resistance 2003).

Results: At baseline, sex ratio was 41/28, median (range) age was 11.3 (0.4 to 18.0) years, CD4 % was 14 (0 to 42) and log₁₀ viral load was 5.0 (1.5 to 6.1) copies/mL. Median number of prior PI and baseline PI mutations were 1 (0 to 5) and 2.5 (0 to 9), respectively. The virological response was observed for 90% of PI-naive and 56% of PI-experienced children (p <0.006). At month 6, the % of CD4 and the viral load in children with success versus failure were 24,7% vs 16,6% (p <0.005) and 1.64 log vs 4.39 log (p <0.001), respectively. Among parameters studied: young age (9.3 vs 11.9 years, p <0.04), PI-naive (p <0,02) and particularly RTV- or APV-naive (p <0.001), and LPV mutation score <4 mutations (p <0.001) were severely associated to the virological success. Only in PI-experienced children, the success was also associated to higher LPV C_max (12.0 vs 7.8 mg/mL, p <0.02). At time of virological failure, accumulation of PI major mutations was observed in 36% (8/22) of cases and the resistance mutations more often selected were at codons 10, 46, and 54. The PI mutations accumulation was correlated with the number of prior PI use and with the number of replication weeks above 1000 copies/mL under LPV/r therapy.

Conclusions:  This study showed a durable antiviral activity of LPV/r in PI-naive and -experienced HIV-1-infected children. Despite the high genetic barrier of the co-formulation LPV/r, the risk of new resistance mutation selection exist and increase with the duration of viral replication above 1000 copies/mL under therapy.

Keywords: lopinavir; children; resistance