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


METHODS
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).


CONCLUSIONS
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.
Bisset
L R
LR
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Cone
R W
RW
Huber
W
W
Battegay
M
M
Vernazza
P L
PL
Weber
R
R
Grob
P J
PJ
Opravil
M
M
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000208:Acute Disease; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D015415:Biomarkers; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000276:immunology; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015415:Biomarkers; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D017493:Leukocyte Common Antigens; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D019438:Ritonavir