We carried out a longitudinal study to analyze the immune recovery of four patients with aggressive HIV-associated lymphoma (HIV+ Ly+) treated with highly active antiretroviral therapy (HAART) and high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT). We also studied three control non-HIV-infected patients with lymphoma (HIV-Ly+) and six HIV patients on HAART without lymphoma (HIV+ Ly-). After 12 months of follow-up, the HIV HIV+Ly+ patients reached the pre-ASCT CD4+ levels, despite a transient decrease after the ASCT. All ASCT patients (HIV+Ly+ and HIV-Ly+) showed an increase in CD4+, CD4+ CD45RO+, and CD4+CD28+ T cells/microl. Although HIV+Ly+ patients had values of CD4+, CD4+CD45RO+, and CD4+CD28+ T cells/microl lower than the HIV-Ly+ patients, their recovery rate over the 12 months after ASCT appeared to be better. HIV+Ly+ patients had higher pre-ASCT plasma IL-7 levels than HIV-Ly+, however, these values decreased after ASCT. All ASCT patients showed a slight increase of TCR rearrangement excision circles (TRECs) and they did not have a different pattern of TREC evolution. We could not find differences between HIV+Ly+ patients 12 months after ASCT and HIV+Ly- in DNA-HIV (copies/10(6) cell). Overall, HIV+Ly+ patients showed an appropriate immune reconstitution 12 months after ASCT, and, interestingly, they had an amount of DNA-HIV copies similar to HIV+Ly- control patients in their CD4+ cells.