Baseline Naive CD4+ T-cell Level Predicting Immune Reconstitution in Treated HIV-infected Late Presenters.
BACKGROUND
Among HIV-infected patients initiating antiretroviral therapy (ART), early changes in CD4+ T-cell subsets are well described. However, HIV-infected late presenters initiating treatment present with a suboptimal CD4+ T-cell reconstitution and remain at a higher risk for AIDS and non-AIDS events. Therefore, factors associated with CD4+ T-cell reconstitution need to be determined in this population, which will allow designing effective immunotherapeutic strategies.


METHODS
Thirty-one adult patients with baseline CD4+ T-cell count <350 cells/mm3 exhibiting viral suppression after ART initiation were followed in the HIV/AIDS research center of Peking Union Medical College Hospital in Beijing, China, from October 2002 to September 2013. Changes in T-cell subsets and associated determinants were measured.


RESULTS
Median baseline CD4+ T-cell count was 70 cells/mm3. We found a biphasic reconstitution of T-cell subsets and immune activation: a rapid change during the first 6 months followed by a more gradual change over the subsequent 8 years. Baseline CD4+ T-cell count >200 cells/mm3 in comparison to CD4+ T-cell count ≤200 cells/mm3 was associated with more complete immune Reconstitution (77.8% vs. 27.3% respectively; P = 0.017) and normalized CD4/CD8 ratio. We showed that the baseline percentage of naive CD4+ T-cell was a predictive marker for complete immune reconstitution (area under receiver operating characteristic curve 0.907), and 12.4% as cutoff value had a sensitivity of 84.6% and a specificity of 88.2%.


CONCLUSIONS
Baseline naive CD4+ T-cell percentage may serve as a predictive marker for optimal immune reconstitution during long-term therapy. Such study findings suggest that increasing thymic output should represent an avenue to improve patients who are diagnosed late in the course of infection.
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Fu-Ping
FP
Guo
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Yi-Jia
YJ
Li
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Zhi-Feng
ZF
Qiu
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Wei
W
Lv
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Yang
Y
Han
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Jing
J
Xie
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Yan-Ling
YL
Li
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Xiao-Jing
XJ
Song
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Shan-Shan
SS
Du
Division of Hematology, Research Institute and Chronic Viral Illness Service, McGill University, Montreal, Quebec, Canada.
Vikram
V
Mehraj
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Tai-Sheng
TS
Li
Division of Hematology, Research Institute and Chronic Viral Illness Service, McGill University, Montreal, Quebec, Canada.
Jean-Pierre
JP
Routy
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D008297:Male; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology