Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: results of AIDS Clinical Trials Group Protocol 315.
Human immunodeficiency virus (HIV)-1 infection is associated with progressive cell-mediated immune deficiency and abnormal immune activation. Although highly active antiretroviral therapy regimens can increase circulating CD4 T lymphocyte counts and decrease the risk of opportunistic complications, the effects of these treatments on immune reconstitution are not well understood. In 44 persons with moderately advanced HIV-1 infection, after 12 weeks of treatment with zidovudine, lamivudine, and ritonavir, plasma HIV-1 RNA fell a median of 2.3 logs (P < .0001). Circulating numbers of naive and memory CD4 T lymphocytes (P < .001), naive CD8 T lymphocytes (P < .004), and B lymphocytes (P < .001) increased. Improved lymphocyte proliferation to certain antigens and a tendency to improvement in delayed-type hypersensitivity also were seen. Dysregulated immune activation was partially corrected by this regimen; however, the perturbed expression of T cell receptor V regions in the CD4 and CD8 T lymphocyte populations was not significantly affected. Ongoing studies will ascertain if longer durations of virus suppression will permit more complete immune restoration.
Lederman
M M
MM
Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Ohio 44106, USA. MXL6@po.cwru.edu
Connick
E
E
Landay
A
A
Kuritzkes
D R
DR
Spritzler
J
J
St Clair
M
M
Kotzin
B L
BL
Fox
L
L
Chiozzi
M H
MH
Leonard
J M
JM
Rousseau
F
F
Wade
M
M
Roe
J D
JD
Martinez
A
A
Kessler
H
H
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D006968:Hypersensitivity, Delayed; D019259:Lamivudine / Q000627:therapeutic use; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D000941:Antigens; D015488:HIV Antigens; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019438:Ritonavir