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This study investigated working memory (WM) training for adolescents with perinatal HIV infection, since WM is negatively impacted by the virus, and adolescence is a time of considerable brain reorganization, during which WM functioning reaches maturation. We posed three main questions: 1) whether WM could be trained in adolescents living with HIV, and if so, whether these effects were maintained over a six-month period during which no further training was received; 2) whether there were differential effects of training on the components of WM (verbal and visuospatial storage, verbal and visuospatial processing); 3) whether the WM training transferred to cognate tasks, and if so, whether these transfer effects were maintained over six months. Sixty-three HIV+ adolescents (10–16 years) from two children's homes were assigned to the training (n = 31) or control (n = 32) group. The training group received 32 hours of supervised training in an adaptive, computerized WM intervention, while the control group received a supervised, placebo computerized program for the same hours. Comprehensive WM and neuropsychological batteries were administered to both groups at pretest, immediately following the intervention, and six months later. Significant improvements were found in verbal WM for the training group, which were maintained six months later. Transfer effects were evident in attention, executive function, memory, language and fluid intelligence. There were no significant posttest improvements in visuospatial storage, and minimal changes in verbal storage and visuospatial WM. These findings represent an important step in exploring ways to improve cognitive functioning in an at-risk population. [ABSTRACT FROM AUTHOR]