High baseline body mass index predicts recovery of CD4+ T lymphocytes for HIV/AIDS patients receiving long-term antiviral therapy

PLOS ONE RESEARCH ARTICLE High baseline body mass index predicts recovery of CD4+ T lymphocytes for HIV/AIDS patients receiving long-term antiviral therapy Jiawen Zhu ID1,2☯, Haimei Huang1☯, Min Wang1, Yun Zhang1, Jinli Mo1,2, Weiyi Tian1, Sumin Tan1, Li Jiang1, Zhihao Meng3*, Shanfang Qin3*, Chuanyi Ning ID1,2* a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Nursing College, Guangxi Medical University, Nanning, Guangxi, China, 2 The Second Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China, 3 Chest Hospital of Guangxi Zhuang Autonomous Region, Liuzhou, Guangxi, China ☯ These authors contributed equally to this work. * (CN); (SQ); (ZM) Abstract OPEN ACCESS Citation: Zhu J, Huang H, Wang M, Zhang Y, Mo J, Tian W, et al. (2022) High baseline body mass index predicts recovery of CD4+ T lymphocytes for HIV/AIDS patients receiving long-term antiviral therapy. PLoS ONE 17(12): e0279731. https://doi. org/10.1371/journal.pone.0279731 Editor: Chika Kingsley Onwuamah, Nigerian Institute of Medical Research, NIGERIA Received: July 22, 2022 Accepted: December 14, 2022 Published: December 30, 2022 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0279731 Copyright: © 2022 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All data generated or analyzed during this study are included in this published article. There are no publicly available data or materials. The relationship between baseline BMI and CD4+ T cells during follow-up in HIV patients in China requires further evaluation. We conducted a retrospective cohort study based on adult AIDS patients who underwent or received antiretroviral therapy from 2003 to 2019 in Guangxi, China. BMI was divided into categories and compared, and after adjusting for BMI being related to the change in CD4 lymphocyte count, with normal weight as the reference group, the BMI before treatment was positively correlated with the changes in CD4+ T cells at different time periods. Among them, obese patients had significant CD4+ cell gain. In patients with pretreatment CD4+ T lymphocyte counts <200 cells/μL, a higher BMI was associated with an increased likelihood of achieving immunologic reconstitution [�350 cells/ μL: AHR: 1.02(1.01, 1.04), P = 0.004; �500 cells/μL: AHR: 1.03 (1.01, 1.05), P = 0.004]. Underweight in HIV patients was a risk factor for poor viral suppression [AHR: 1.24 (1.04, 1.48), P = 0.016]. Our study demonstrated that HIV/AIDS patients receiving ART with higher baseline BMI had better immune reconstitution and that baseline BMI could be an important predictor of immune reconstitution in patients receiving ART. Baseline BMI was not associated with virological failure, but a lower baseline BMI indicated poor viral suppression during follow-up. Introduction In the antiretroviral therapy (ART) era, higher opportunistic infection and mortality rates are associated with immunodeficiency [1–3]. With the success of ART, the pathogen-specific immune recovery of the human body is promoted, thereby reducing the morbidity and mortality of AIDS- and non-AIDS-associated diseases [4]. CD4+ T lymphocyte counts are repeated at least once a year to monitor the efficacy after treatment, and continuous monitoring of peripheral CD4+ T cells in patients receiving long-term ART is important for understanding the disease progression of HIV infections [5, 6]. PLOS ONE | https://doi.org/10.1371/journal.pone.0279731 December 30, 2022 1 / 18 PLOS ONE Funding: This study received support from the National Natural Science Foundation of China (Grant Nos. 81803295 and 81760602), the Natural Science Foundation of Guangxi (2018GXNSFAA138031), the “Thirteenth FiveYear” National Major Science and Technology Projects (2018ZX10715008–002 and 2018ZX10302104–001), the Innovation Project of Guangxi Graduate Education (YCSW2021143), and the Opening topic fund of Guangxi Key Laboratory of AIDS Prevention and Treatment (No.gklapt 201902). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Abbreviations: BMI, Body mass index; HIV, human immunodeficiency virus; AIDS, Acquired Immune Deficiency Syndrome; WHO, World Health Organization; ART, antiretroviral therapy; VL, viral load; HR, hazard ratio; AHR, adjusted hazard ratio; CI, confidence interval; LOESS, local polynomial regression fitting. BMI predicts recovery of CD4+ T lymphocytes While the virus is completely suppressed, HIV-infected patients’ CD4+ T lymphocyte count will gradually increase by 50–150 cells/mm3 per year on average. The CD4+ T-cell count usually increases rapidly in the first 3 months after treatment and gradually increases over time until it reaches the normal value (>500 cells/mm3) and then plateaus [7]. Younger age and lower viral load were associated with a large gain in CD4+ T cells during ART follow-up [8–10]. A previous study used a semimechanistic population model to describe the trajectories of CD4+ T cells after treatment in HIV-infected patients, suggesting that older age is a risk factor for immune reconstitution in HIV patients [11]. The model results showed that the percentage difference of patients aged � 50 years achieving adequate immune reconstitution (CD4 + T-cell count > 500 cell/μL) was 15%, 21%, and 26% in the first year, fourth year, and steady-state, respectively, compared with patients aged 18–35 years. A 10-year cohort study [10] of HIV-infected injection drug users from the Asia-Pacific region reported that patients with a viral load of �400 copies/mL during follow-up had a greater increase in CD4 cell count over time. Decreased ten-year mean levels of CD4+ T-cell change in patients with viral loads of 401 to 100,000 copies/mL (-65.3, 95% CI: -106.6, -23.9) and >100,000 copies/mL (-121.4, 95% CI: -176.0, -66.7) were compared with patients with viral loads of �400 copies/mL. Body mass index (BMI) is associated with immune reconstitution in antiviral therapy patients. Our results demonstrate that overweight HIV-infected individuals who were obese at diagnosis had greater increases in CD4 counts over time than overweight and normal weight at diagnosis [12]. A retrospective cohort study of HIV referral centres in Singapore found no association between BMI and the magnitude of change in immune recovery [13]. Several studies have (...truncated)