Observational Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2023; 14(3): 299-312
Published online Mar 15, 2023. doi: 10.4239/wjd.v14.i3.299
Glucose metabolism continuous deteriorating in male patients with human immunodeficiency virus accepted antiretroviral therapy for 156 weeks
Da-Feng Liu, Xin-Yi Zhang, Rui-Feng Zhou, Lin Cai, Dong-Mei Yan, Li-Juan Lan, Sheng-Hua He, Hong Tang
Da-Feng Liu, Li-Juan Lan, Department of Internal Medicine, Public Health and Clinical Center of Chengdu, Chengdu 610061, Sichuan Province, China
Xin-Yi Zhang, Department of Endocrinology and Metabolism, Sichuan University West China Hoapital, Chengdu 610041, Sichuan Province, China
Rui-Feng Zhou, Lin Cai, Dong-Mei Yan, Sheng-Hua He, Department of Infectious Disease, Public Health and Clinical Center of Chengdu, Chengdu 610061, Sichuan Province, China
Hong Tang, Center of Infectious Disease, Sichuan University West China Hoapital, Chengdu 610041, Sichuan Province, China
Author contributions: Liu DF, Zhang XY, Zhou RF, Cai L, Yan DM, Lan LJ, He SH and Tang H contributed concept and design; Liu DF, Zhang XY, Zhou RF, Cai L, Yan DM and Lan LJ contributed data acquisition; Liu DF, Zhang XY, Zhou RF, Cai L, Yan DM and Lan LJ contributed data analysis and interpretation; Liu DF, Zhang XY, Zhou RF, Cai L, Yan DM and Lan LJ contributed drafting of the manuscript; Liu DF, Zhou RF, Cai L, Yan DM, Lan LJ, He SH and Tang H contributed administrative, technical, or material support; He SH and Tang H contributed study supervision.
Supported by The Twelfth Five-Year Project on Tackling Key Problems of National Science and Technology, No. 2012ZX10001-003; Sichuan Province Health Commission, No. 130430 and No. 17PJ070; and Chengdu Municipal Health Commission, No. 2019079.
Institutional review board statement: The study was approved by the hospital ethics committee of the Public and Health Clinic Centre of Chengdu (PJ-K2012-012-01).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data, models, or code generated or used during the study are available from the corresponding author by request: Liu DF, E-mail: liudf312@126.com.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Da-Feng Liu, MD, Chief Physician, Department of Internal Medicine, Public Health and Clinical Center of Chengdu, No. 377 Jingming Road, Jinjiang District, Chengdu 610061, Sichuan Province, China. ldf312@126.com
Received: October 1, 2022
Peer-review started: October 1, 2022
First decision: December 12, 2022
Revised: December 21, 2022
Accepted: February 27, 2023
Article in press: February 27, 2023
Published online: March 15, 2023
Processing time: 165 Days and 8.1 Hours
ARTICLE HIGHLIGHTS
Research background

Antiretroviral therapy (ART) is currently the most effective treatment for acquired immune deficiency syndrome (AIDS), as it can prolong life expectancy and improve quality of life. However, non-AIDS-related diseases, such as metabolic abnormalities, osteoporosis and cardiovascular diseases, have become essential factors affecting the prognosis of AIDS patients. Disorders of glucose metabolism are common metabolic diseases and risk factors for cardiovascular disease. No reports about the long-term dynamic characteristics of glucose metabolism after ART with a specific regimen as the efavirenz (EFV) plus lamivudine (3TC) plus tenofovir (TDF) (EFV + 3TC + TDF) regimen were found in the literature.

Research motivation

As one of the first-line ART programs since the National Twelfth Five-Year Plan in China, the EFV + 3TC + TDF regimen has been used for more than ten years and has a reduced effect on metabolism, and there are few reports about its effect on glucose metabolism in the literature. Our previous study showed that the fasting plasma glucose (FPG) level increased within four weeks and then returned to the baseline level at 12 wk after ART with the EFV + 3TC + TDF regimen, especially in patients with CD4+ counts less than 350 cells/μL. However, the long-term dynamic characteristics of glucose metabolism and its contributing factors in such patients treated with the EFV + 3TC + TDF regimen are unclear and warrant further examination.

Research objectives

This study aimed at the long-term dynamic characteristics of glucose metabolism and its contributing factors in male patients living with human immunodeficiency virus (PLWH) who accepted primary treatment with the EFV + 3TC + TDF regimen for 156 wk.

Research methods

This study was designed using a follow-up design. Sixty-one male treatment-naïve PLWH, including 50 cases with normal glucose tolerance and 11 cases with prediabetes, were treated with the EFV + 3TC + TDF regimen for 156 wk. The glucose metabolism dynamic characteristics, the main risk factors and the differences among the three CD4+ count groups were analyzed.

Research results

In treatment-naive male PLWH, regardless of whether glucose metabolism disorder was present at baseline, who accepted treatment with the EFV + 3TC + TDF regimen for 156 wk, a continuous increase in the FPG level, the rate of IFG and the HbA1c level were found. These changes were not due to insulin resistance but rather to significantly reduced islet β cell function, according to HOMA-β. Moreover, the lower the baseline CD4+ T-cell count was, the higher the FPG level and the lower the HOMA-β value. Furthermore, the main risk factors for the FPG levels were the CD3+CD8+ cell count and VL, and the factors contributing to the HOMA-β values were the alanine aminotransferase level, VL and CD3+CD8+ cell count.

Research conclusions

These findings provide guidance to clinicians who are monitoring FPG levels closely and are concerned about IFG and decreased islet β cell function during ART with the EFV + 3TC + TDF regimen for long-term application.

Research perspectives

To our knowledge, this prospective 3-year follow-up cohort study is the first to report the long-term dynamic effects of the TDF + 3TC + EFV regimen and the baseline CD4+ T cell count on glucose metabolism in male PLWH. The results showed that in male PLWH who were TDF + 3TC + EFV regimen treatment-naïve for 3 years, glucose metabolism continuously deteriorated, as shown by gradual increases in the FPG level, IFG rate and HbA1c level, regardless of whether glucose metabolism disorder was present at baseline, and the change was not due to insulin resistance but rather to significantly reduced islet β cell function. Moreover, the lower the baseline CD4+ T cell count was, the higher the FPG level and the lower the HOMA-β value were. These findings should encourage clinicians to monitor the FPG level closely and to be concerned about the IFG rate and decreased islet β cell function in patients who receive long-term TDF + 3TC + EFV regimen treatment.