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

Publication

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

Journal Paper/Review - Nov 12, 1998

Bisset L R, Cone R W, Huber W, Battegay M, Vernazza Pietro, Weber R, Grob P J, Opravil M

Units

Division of Infectious Diseases, Infection Prevention and Travel Medicine

PubMed

9833852

Citation

Bisset L, Cone R, Huber W, Battegay M, Vernazza P, Weber R, Grob P, Opravil M. Highly active antiretroviral therapy during early HIV infection reverses T-cell activation and maturation abnormalities. Swiss HIV Cohort Study. AIDS (London, England) 1998; 12:2115-23.

Type

Journal Paper/Review (English)

Journal

AIDS (London, England) 1998; 12

Publication Date

Nov 12, 1998

Issn Print

0269-9370

Pages

2115-23

Brief description/objective

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 > or = 400 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; CD8+ cells, 894 x 10(6)/l; plasma HIV RNA, 3.93 log10 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. 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 < or = 0.05), CD8+/HLA-DR+ (maximum change, -66%; P < or = 0.005) and CD8+/CD38+ (maximum change, -51%; P < or = 0.01) T cells. A concomitant significant increase in numbers of naive CD4+/CD45RA+ (maximum change, +12%; P < or = 0.005) and memory CD4+/CD45RO+ (maximum change, +6%; P < or = 0.05) T cells was also evident, which contrasted with a significant decrease in memory CD8+/CD45RO+ cells (maximum change, -42%; P < or = 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.