Long-term evaluation of T-cell subsets and T-cell function after HAART in advanced stage HIV-1 disease.
OBJECTIVE
Evaluation of immunological reconstitution after 2 years of highly active antiretroviral therapy (HAART) in AIDS patients.


METHODS
Previous data showed the effectiveness of HAART but conflicting evidence of immune reconstitution has been found in severely immunocompromised patients. Therefore, T-cell subsets and functions were analysed during 24 months of HAART in 21 AIDS patients (mean baseline CD4 cell count, 20 x 10(6)/l).


METHODS
Subjects were tested at baseline and after 4, 12 and 24 months of therapy for clinical symptoms and the following investigations were carried out: plasma HIV RNA, T-cell subsets and lymphoproliferative responses to mitogens (phytohaemagglutinin, anti-CD3), and recall antigens (Candida mannoprotein, tetanus toxoid and recombinant glycoprotein 160).


RESULTS
Increase in body weight, improvement of Karnofsky's score and reduction of opportunistic infections were observed. All patients showed an initial increase in the CD4 memory subset, whereas naive CD4 cells consistently increased only after 1 year. The magnitude of immune recovery was stronger in patients showing a significant reduction in viral load. However seven out of 21 patients who did not reach a sustained suppression of viral load showed also an increase in T-cell subsets. The majority of patients recovered lymphoproliferative responses to mitogens, whereas only four subjects showed a functional response to Candida mannoprotein. No patients showed a response to HIV recombinant glycoprotein 160 or tetanus toxoid.


CONCLUSIONS
The immune recovery observed is slower and not complete in severely immunocompromised patients. Our data suggest that HAART may be continued also in the absence of a significant HIV RNA decrease if alternative drugs are not available.
Department of Clinical Medicine, University of Rome, La Sapienza, Italy.
I
I
Mezzaroma
M
M
Carlesimo
E
E
Pinter
C
C
Alario
G
G
Sacco
D S
DS
Muratori
M L
ML
Bernardi
R
R
Paganelli
F
F
Aiuti
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D017951:Antigen Presentation; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D006968:Hypersensitivity, Delayed; D007156:Immunologic Memory; D019469:Indinavir / Q000627:therapeutic use; D008213:Lymphocyte Activation; 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*; D013601:T-Lymphocytes / Q000276:immunology*
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir; D019438:Ritonavir