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

Objectives: 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. Design: 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 300 x 10(6)/l. Methods: Peripheral blood CD4+ and CD8+ T cells derived from 15 asymptomatic HIV-infected individuals (median baseline CD4+ cells, 608 x 10(6)/l; CD8s cells, 894 x 10(6)/l; plasma HIV RNA, 3.93 log(10) copies/ml) undergoing therapy with zidovudine (300 mg twice daily), lamivudine (150 mg twice daily), and ritonavir (600 mg twice daily) were assessed Cor changes in expression of phenotypic markers of T-cell activation (HLA-DR and CD38) and maturation (CD45RA and CD35RO). 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. Results: 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 I 0.05) T cells was also evident, which contrasted with a significant decrease in memory CD8+/CD45RO+ cells (maximum change, -42%; P < 0.005). Conclusion: 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. (C) 1998 Lippincott Williams & Wilkins