Research Paper Volume 14, Issue 23 pp 9647—9667

The pattern and magnitude of T cell subsets reconstitution during ten years of ART with viral suppression in HIV-infected patients

Lianfeng Lu1, , Xiaodi Li1, , Xiaosheng Liu2, , Zhifeng Qiu1, , Yang Han1, , Xiaojing Song1, , Yanling Li1, , Xiaoxia Li1, , Wei Cao1, , Wei Lv1, , Zhihui Dou3, , Taisheng Li1,2,4, &, ,

  • 1 Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
  • 2 Tsinghua-Peking Center for Life Sciences, Beijing, China
  • 3 National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
  • 4 State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

Received: June 7, 2022       Accepted: November 14, 2022       Published: December 9, 2022
How to Cite

Copyright: © 2022 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: The extent of immune reconstitution in human immunodeficiency virus (HIV) infected persons receiving long-term antiretroviral therapy (ART) with controlled viral load has been controversial. We studied the extent and speed of T cell subsets retrieval after long-term antiretroviral treatment.

Methods: 662 HIV-infected patients followed at least 2 years whose plasma HIV-1 RNA load <50 copies/mL were evaluated for longitudinal and functional phenotypic indices of immune restoration. Determinants of change in magnitude and importance of recovery have been evaluated using mixed linear regression models.

Results: Almost all robust immune restorations achieved occurred after 2–3 years of ART. The median CD4 lymphocyte count increased 449 cells/μl (IQR 303–604) from 226 cells/μl (IQR 83–336) at baseline during the third year (P < 0.001); CD4+T lymphocyte rises during the sixth and tenth years were not significant. Naive and memory CD4+T cells‘reconstitution occurred in the sixth and eighth years of ART but no significant change thereafter. The change of CD45RA+Naïve and CD45RA-memory CD4+T cell reconstitution is different in baseline CD4+T cell counts <100 cells/μl group and in baseline CD4+T cell counts >100 cells/μl group. Activation antigen expression (CD38 or HLA-DR) on CD8 lymphocytes declined mostly during the first till second year, and after 4 years, activation antigen expression on patient lymphocytes showed no significant change. The proportion of CD4 cells expressing CD28 climbed during the first years and reached normal levels in the second year.

Conclusions: Immune restoration was dependent on the capacity of immune system during the first 2–3 year of ART. But the significant change of CD4 and compartments of CD4+T cells could persist until 6–8 years. The pattern of CD38+CD8+, HLA-DR+CD8+, CD28+CD4+ T cells could quickly return to normal level and no significant change after sufficient time of ART. In general, the immune response compared to the baseline status may be the overall effect from the age and time of antiretroviral treatment.


HIV-1: human immunodeficiency virus type 1; ART: antiretroviral therapy; NRTIs: Nucleoside reverse-transcriptase inhibitors; NNRTI: Non-Nucleoside reverse-transcriptase inhibitors; PI: Proteinase inhibitor; INSTI: Integrase inhibitor.