Rapid restoration of CD4 T cell subsets in subjects receiving antiretroviral therapy during primary HIV-1 infection.
OBJECTIVE
To compare the effect of highly active antiretroviral therapy on immune reconstitution in subjects with acute and chronic HIV-1 infection.


METHODS
Prospective study including 58 treatment-naive subjects who commenced indinavir or nelfinavir and two nucleosides during primary (PHI; n = 28) or chronic HIV-1 infection (CHI; n = 30).


METHODS
Naive (CD45RA+ 62L+), memory (CD45RA-) and activated (CD38+ HLA-DR+) T cell subsets were quantified at 1-2 monthly time intervals using 4-colour flow cytometry.


RESULTS
At 1 year, HIV-1 RNA declined in both cohorts to undetectable levels (< 50 copies/ml), while median CD4 lymphocyte count increased from 470 to 758 x 10(6) cells/l in PHI and from 204 to 310 x 10(6) cells/l in CHI, reaching > 500 x 10(6) cells/l in 93% of PHI, but only in 37% of CHI subjects (P < 0.001). Naive CD4 lymphocytes increased from 106 to 176 x 10(6) cells/l in PHI and from 41 to 44 x 10(6) cells/l in CHI (PHI versus CHI at 12 months: P = 0.003), while memory cells rose from 368 to 573 x 10(6) cells/l in PHI and from 148 to 223 x 10(6) cells/l in CHI (P < 0.001). Early increases (< 3 months) of CD4 lymphocytes were larger in subjects with PHI, consisting of naive CD45RA+ CD62L+ as well as memory CD45RA- CD62L+ cells (P = 0.001). CD4 activation declined from 5 to 2% in PHI and from 13 to 6% in CHI (P = 0.001), while CD8 cell activation was reduced from 33 to 15% in PHI and from 42 to 19% in CHI (P = 0.02).


CONCLUSIONS
Immune reconstitution was more complete, occurred earlier and comprised both naive and memory CD4 T lymphocytes in subjects who commenced antiretroviral therapy during primary HIV-1 infection.
Kaufmann
G R
GR
National Centre in HIV Epidemiology and Clinical Research, Sydney, NSW, Australia.
Zaunders
J J
JJ
Cunningham
P
P
Kelleher
A D
AD
Grey
P
P
Smith
D
D
Carr
A
A
Cooper
D A
DA
D000208:Acute Disease; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors
D019380:Anti-HIV Agents; D012367:RNA, Viral