Highly active antiretroviral therapy during early HIV infection reverses T-cell activation and maturation abnormalities

Our objectives were to evaluate the impact of early initiation of highly active antiretroviral therapy (HAART) on disease-induced T-cell activation and maturation abnormalities during asymptomatic HIV infection. A prospective open-label trial of zidovudine, lamivudine and ritonavir in treatment-naive asymptomatic HIV-infected individuals with CD4 cells greater than or equal to 400 x 10 super(6)/l. Peripheral blood CD4+ and CD8+ T cells derived from 15 asymptomatic HIV-infected individuals (median baseline CD4+ cells, 608 x 10 super(6)/l; CD8+ cells, 894 x 10 super(6)/l; plasma HIV RNA, 3.93 log sub(10) copies/ml) undergoing therapy with zidovudine (300 mg twice daily), lamivudine (150 mg twice daily), and ritonavir (600 mg twice daily) were assessed for changes in expression of phenotypic markers of T-cell activation (HLA-DR and CD38) and maturation (CD45RA and CD45RO). At weeks 0, 2, 4, 8, 12, 16, 20 and 24, T-cell subsets were quantified by flow cytometry and plasma HIV viral loads determined using reverse transcription PCR. HAART-induced decrease in plasma HIV RNA levels coincided with a significant reduction in numbers of activated CD4+/HLA-DR+ (maximum change, -36%; P less than or equal to 0.05), CD8+/HLA-DR+ (maximum change, -66%; P less than or equal to 0.005) and CD8+/CD38+ (maximum change, -51%; P less than or equal to 0.01) T cells. A concomitant significant increase in numbers of naive CD4+/CD45RA+ (maximum change, +12%; P less than or equal to 0.005) and memory CD4+/CD45RO+ (maximum change, +6%; P less than or equal to 0.05) T cells was also evident, which contrasted with a significant decrease in memory CD8+/CD45RO+ cells (maximum change, -42%; P less than or equal to 0.005). The observed ability of HAART during early asymptomatic HIV infection to initiate rapid reversal of disease-induced T-cell activation and maturation abnormalities, while preserving pretherapy levels of immune function, supports the concept that therapeutic advantage is to be gained by commencing early aggressive antiretroviral therapy.