Immune reconstitution after 2 years of successful potent antiretroviral therapy in previously untreated human immunodeficiency virus type 1-infected adults.
Today's antiretroviral combination regimens can induce significant and sustained decreases in human immunodeficiency virus (HIV)-RNA levels, allowing the immune system to recover. To what extent immune reconstitution is possible and what factors determine the outcome have thus far not been resolved. We studied 19 subjects, treated for 2 years with protease inhibitor-containing triple therapy, who had a strong suppression of HIV-RNA levels. CD4+ T-cell numbers increased from medians of 170 to 420x106 cells/L, but in a number of subjects T-cell numbers did not further increase after week 72, without having reached normal values. Long-term CD4+ T-cell change was mainly caused by a slow but continuous increase in naive CD4+ T cells (CD45RA+CD62L+) and was predicted by the baseline number of these cells. Our data indicate that long-term immunological recovery is gradual, even during strong suppression of viral replication, not always complete, and dependent on the preexisting level of naive CD4+ T cells.
Notermans
D W
DW
National AIDS Therapy Evaluation Centre (NATEC), Academic Medical Centre, 1100 DE, Amsterdam, The Netherlands. D.W.Notermans@amc.uva.nl
Pakker
N G
NG
Hamann
D
D
Foudraine
N A
NA
Kauffmann
R H
RH
Meenhorst
P L
PL
Goudsmit
J
J
Roos
M T
MT
Schellekens
P T
PT
Miedema
F
F
Danner
S A
SA
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D015497:HIV-1; D006801:Humans; D007156:Immunologic Memory; D019259:Lamivudine / Q000627:therapeutic use; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D012016:Reference Values; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019438:Ritonavir