Simplified triple NRTI regimen effective in vertically infected children: two years follow-up

Guido Castelli-Gattinara from Bambino Gesu hospital in Rome presented findings from a study evaluating a switch from protease based HAART to a simplified triple nucleoside regimen in a group of 20 vertically infected children.

The aim of the study was to evaluate long-term capacity to control viral replication; maintain immune reconstitution; reduce toxicity and improve quality of life.

Children with at least 24 months of undetectable viral load (<50 copies/mL) during PI-based treatment were enrolled in this single-arm non-randomised study. The triple nucleoside regimen was either AZT or d4T, plus abacavir and 3TC.

The childrens median age at switch was 8.1 years (range 3-18 years) and mean length of PI-based HAART was 50 months. Of 20 patients, 7 were treated since the first months of age; 8 were symptomatic when treated and 6 presented with severe immune deficiency prior to starting HAART.

At study entry, all children had undetectable viral load for a median of 36 months; a good CD4 percentage (mean 34.5%), good clinical health, and normal growth percentiles.

After a median follow up of 108 weeks (60 to 132 weeks), of triple nucleoside treatment all but one patient maintained undetectable viral load, plus good CD4 percentages, clinical and growth parameters. The one virological failure was in an adolescent boy who stopped treatment for personal reasons. The investigators attributed this failure to the development of the M184V mutation (M361/M and L63P mutations were also observed).

The investigators reported that after a median of 60 weeks, 8/20 children (40%) experienced blips (viral load >50 and <1000 copies/mL), but returned to undetectable levels. Additionally they found that total cholesterol decreased from a mean of 187 to 147 mg/dL, LDL decreased from 113 to 81 mg/dL, and triglycerides from 91.8 to 74mg/dL. They also found a progressive increase of specific CTL response in some children.

The researchers concluded that in this small study: HAART simplification after an induction therapy allows to maintain a complete and long-term immunological and virological control with significant improvement of dyslipidemia. The progressive increase of specific cytotoxic T-lymphocyte response observed in some patients can be related to an enhanced viral replication in lymph nodes or an increased frequency of blips.

Castelli-Gattinara G, Amicosante M, Palma P et al. 3-NRTI HAART simplification in children Is effective in maintaining virological and immunological control after 108 weeks. 13th CROI, Denver, 2006. Abstract 18.