Immunological recovery despite virological failure is independent of human immunodeficiency virus-type 1 resistant mutants in children receiving highly active antiretroviral therapy

Relationships between human immunodeficiency virus-type-1 (HIV-1) drug-resistant mutants and immunological recovery were investigated after 12-week antiretroviral therapy in 43 children infected perinatally with virological failure. Twenty-two children received highly active antiretroviral therapy (HAART) and 21 received double therapy with reverse transcriptase inhibitors. At baseline, no difference in reverse transcriptase or protease inhibitors resistant mutants was present among the groups. After 12 weeks, the two groups were similar regarding proportion of children with reverse transcriptase resistant mutants. Sixteen (73%) HAART-treated children, but no child receiving double therapy had HIV-1 with primary resistance mutations to protease inhibitors. Secondary protease mutations were found in all HAART-treated and in 17/21 (81%) children receiving double therapy. The mutation numbers in reverse transcriptase or protease genes were significantly higher after HAART than after double therapy. Nevertheless, 12 (55%) of HAART-treated children (but no child receiving double therapy) showed immunological recovery. The frequency and number of mutations were similar in HAART-treated children with or without immunological recovery both at baseline and after 12 weeks. The findings suggest, immunological recovery notwithstanding, virological failure is independent of drug-resistant mutations and consequent possible changes in viral fitness. (C) 2003 Wiley-Liss, Inc.