The objective of this study was to assess the impact of highly active antiretroviral therapy (HAART) by an oral route on the peripheral blood CD8 subset in the monkeys infected persistently with a pathogenic strain, SHIV 8 9 . 6 P . Two rhesus macaques were inoculated intravenously with SHIV 8 9 . 6 P , then treated with the combination of AZT, 3TC and Lopinavir/Ritonavir (LPV/RTV) as recommended in humans by the oral route with confectionery continued for 28 days. In one of two chronically infected macaques, MM260, the viral load was maintained in the range of 10 4 -10 5 copies/ml before HAART. The plasma viral load and proviral DNA decreased dramatically during the treatment, and cessation of this therapy the viral load rebounded to the pre-treatment level but the proviral DNA rebound was delayed. The other monkey, MM242, had low viral loads (1.2x10 3 -<5x10 2 copies/ml) both before and after HAART. CD4 + and CD8 + T cell counts and proviral DNA level were not significantly changed after the treatment. The percentages of CD8 + CD45RA - Ki67 + cells increased during (MM260) or after (MM242) HAART and the subset was maintained at a high percentage until 18 weeks post HAART in MM242. These findings suggest that this primate model might serve an important role in testing the virological and immunological efficacy of novel therapeutic strategies combined with HAART.