Lu-Xue Zhang1, Jin-Wen Song2, Chao Zhang2, Xing Fan2, Hui-Huang Huang2, Ruo-Nan Xu2, Jia-Ye Liu2, Ji-Yuan Zhang2, Li-Feng Wang2, Chun-Bao Zhou2, Lei Jin2, Ming Shi2, Fu-Sheng Wang3, Yan-Mei Jiao4. 1. Infectious Disease Department, Xuanwu Hospital, Capital Medical University, Beijing, China; Treatment and Research Center for Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. 2. Treatment and Research Center for Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. 3. Treatment and Research Center for Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. Electronic address: fswang302@163.com. 4. Treatment and Research Center for Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. Electronic address: jiaoyanmei@sina.com.
Abstract
BACKGROUND: The dynamics of viral reservoir decay and naïve CD4 T-cell recovery between immunological non-responders (INR) and complete responders (CR) during long-term antiretroviral treatment (ART) are not fully known. METHODS: Twenty-eight chronic HIV-infected individuals on 5-year ART were divided into two groups: INR (CD4 counts ≤350 cells/μL, n = 13) and CR (CD4 counts ≥500 cells/μL, n = 15). The levels of HIV DNA and cell-associated HIV RNA (CA-RNA), CD4 counts, naïve CD4 counts and their correlations were analyzed at baseline, years 1, 3 and 5 of ART between the two groups. Expression of PD-1 on CD4 T-cells was quantified by flow cytometry. Linear mixed effect models were used to estimate the change procession in repeated measurements over 5 years. Slopes of the above-mentioned indicators were estimated using participant-specific linear regressions, respectively. RESULTS: INR maintained higher levels of HIV DNA and CA-RNA with higher percentages of PD-1+CD4 T-cells compared with CR during 5-year ART, concurrent with lower naïve CD4 T-cells. However, the rates of HIV DNA and CA-RNA decay in INR were not different from that in CR over time, and INR had higher rates of naïve CD4 T-cell percentage recovery. The baseline levels of HIV DNA were positively associated with the 5-year levels of HIV DNA, but negatively associated with the 5-year naïve CD4 counts. CONCLUSIONS: INR maintained significantly higher viral reservoir and lower naïve CD4 T-cells compared with CR during 5-year ART, however, the rates of reservoir decay and naïve CD4 T-cell percentage growth within INR were not lower than that in CR over time.
BACKGROUND: The dynamics of viral reservoir decay and naïve CD4 T-cell recovery between immunological non-responders (INR) and complete responders (CR) during long-term antiretroviral treatment (ART) are not fully known. METHODS: Twenty-eight chronic HIV-infected individuals on 5-year ART were divided into two groups: INR (CD4 counts ≤350 cells/μL, n = 13) and CR (CD4 counts ≥500 cells/μL, n = 15). The levels of HIV DNA and cell-associated HIV RNA (CA-RNA), CD4 counts, naïve CD4 counts and their correlations were analyzed at baseline, years 1, 3 and 5 of ART between the two groups. Expression of PD-1 on CD4 T-cells was quantified by flow cytometry. Linear mixed effect models were used to estimate the change procession in repeated measurements over 5 years. Slopes of the above-mentioned indicators were estimated using participant-specific linear regressions, respectively. RESULTS: INR maintained higher levels of HIV DNA and CA-RNA with higher percentages of PD-1+CD4 T-cells compared with CR during 5-year ART, concurrent with lower naïve CD4 T-cells. However, the rates of HIV DNA and CA-RNA decay in INR were not different from that in CR over time, and INR had higher rates of naïve CD4 T-cell percentage recovery. The baseline levels of HIV DNA were positively associated with the 5-year levels of HIV DNA, but negatively associated with the 5-year naïve CD4 counts. CONCLUSIONS: INR maintained significantly higher viral reservoir and lower naïve CD4 T-cells compared with CR during 5-year ART, however, the rates of reservoir decay and naïve CD4 T-cell percentage growth within INR were not lower than that in CR over time.
Authors: Kristina Berg Lorvik; Malin Holm Meyer-Myklestad; Kushi Kushekar; Charlotte Handeland; Asle Wilhelm Medhus; Marius Lund-Iversen; Birgitte Stiksrud; Dag Kvale; Anne Margarita Dyrhol-Riise; Kjetil Taskén; Dag Henrik Reikvam Journal: Front Immunol Date: 2021-10-07 Impact factor: 7.561