Baseline Naive CD4+ T-cell Level Predicting Immune Reconstitution in Treated HIV-infected Late Presenters

• Main Authors: Fu-Ping Guo, Yi-Jia Li, Zhi-Feng Qiu, Wei Lv, Yang Han, Jing Xie, Yan-Ling Li, Xiao-Jing Song, Shan-Shan Du, Vikram Mehraj, Tai-Sheng Li, Jean-Pierre Routy
• Format: Article
• Language: English
• Published: Wolters Kluwer 2016-01-01
• Series: Chinese Medical Journal
• Subjects: Antiretroviral Therapy; HIV; Immune Activation; Naive CD4+ T-cell; Thymic Function
• Online Access: http://www.cmj.org/article.asp?issn=0366-6999;year=2016;volume=129;issue=22;spage=2683;epage=2690;aulast=Guo

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.