Immune correlates of CD4 decline in HIV-infected patients experiencing virologic failure before undergoing treatment interruption.
BACKGROUND
The advantage of treatment interruptions (TIs) in salvage therapy remains controversial. Regardless, characterizations of the correlates of CD4 count fall during TI are important to identify since patients with virologic failure commonly stop antiretroviral (ARV) therapy. The objective of this study was to determine the predictive value of pre-TI proliferative capacity and cell surface markers for CD4 count change in HIV-infected patients experiencing virologic failure before undergoing TI.


METHODS
Peripheral blood mononuclear cells (PBMCs) from 13 HIV-infected patients experiencing virologic failure at baseline time points before the TI were tested for proliferation using the 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay and a Gag p55 peptide pool, staphylococcus enterotoxin B (SEB), cytomegalovirus (CMV) recall antigen, and anti-CD3 antibody as stimuli. CD28 and CD57 expression on CD4+ and CD8+ T-cells was measured.


RESULTS
The median changes in the CD4+ T-cell count and viral load from baseline to the TI time point corresponding to the CD4 count nadir were -44 cells/mm3 {Interquartile range (IQR) -17, -104} and +85,332 copies/mL (IQR +11,198, +283,327), respectively. CD4+ T-cell proliferation to CMV, pre-TI CD4+ T-cell count, and percent CD4+CD57+ cells correlated negatively with CD4 count change during TI (r = -0.59, p = 0.045, r = -0.61, p = 0.030 and r = -0.69, p = 0.0095, respectively; Spearman correlation). The presence of HIV-specific proliferative responses was not associated with a reduced decline in CD4 count during TI.


CONCLUSIONS
The use of pre-TI immune proliferative responses and cell surface markers may have predictive value for CD4 count decline during TI.
Huang
Kenneth H
KH
Research Institute of McGill University Health Center, Montreal, Quebec, Canada. kenneth.huang@mail.mcgill.ca <kenneth.huang@mail.mcgill.ca>
Loutfy
Mona R
MR
Tsoukas
Christos M
CM
Bernard
Nicole F
NF
D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018959:CD57 Antigens / Q000378:metabolism*; D003587:Cytomegalovirus / Q000276:immunology; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D011237:Predictive Value of Tests; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D016879:Salvage Therapy; D019562:Viral Load
D019380:Anti-HIV Agents; D018959:CD57 Antigens; D018894:Reverse Transcriptase Inhibitors