Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects.
The risks and benefits of structured treatment interruption (STI) in HIV-1-infected subjects are not fully understood. A pilot study was performed to compare STI with continuous highly active antiretroviral therapy (HAART) in chronic HIV-1-infected subjects with HIV-1 plasma RNA levels (VL) <400 copies per ml and CD4(+) T cells >400 per microl. CD4(+) T cells, VL, HIV-1-specific neutralizing antibodies, and IFN-gamma-producing HIV-1-specific CD8(+) and CD4(+) T cells were measured in all subjects. STIs of 1-month duration separated by 1 month of HAART, before a final 3-month STI, resulted in augmented CD8(+) T cell responses in all eight STI subjects (P = 0.003), maintained while on HAART up to 22 weeks after STI, and augmented neutralization titers to autologous HIV-1 isolate in one of eight subjects. However, significant decline of CD4(+) T cell count from pre-STI level, and VL rebound to pre-HAART baseline, occurred during STI (P = 0.001 and 0.34, respectively). CD4(+) T cell counts were regained on return to HAART. Control subjects (n = 4) maintained VL <400 copies per ml and stable CD4(+) T cell counts, and showed no enhancement of antiviral CD8(+) T cell responses. Despite increases in antiviral immunity, no control of VL was observed. Future studies of STI should proceed with caution.
Ortiz
G M
GM
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94141-9100, USA. gortiz@gladstone.ucsf.edu
Wellons
M
M
Brancato
J
J
Vo
H T
HT
Zinn
R L
RL
Clarkson
D E
DE
Van Loon
K
K
Bonhoeffer
S
S
Miralles
G D
GD
Montefiori
D
D
Bartlett
J A
JA
Nixon
D F
DF
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D019562:Viral Load
D015483:HIV Antibodies; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors