Richard M Novak1, Carl Armon2, Linda Battalora2,3, Kate Buchacz4, Jun Li4, Douglas Ward5, Kimberly Carlson2, Frank J Palella6. 1. University of Illinois College of Medicine, Chicago, Illinois. 2. Cerner Corporation, Kansas City, Missouri. 3. Colorado School of Mines, Golden, Colorado. 4. Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia. 5. Dupont Circle Physicians Group, Washington, DC. 6. Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Abstract
BACKGROUND: Age blunts CD4+ lymphocyte cell count/μl (CD4+) improvements observed with antiretroviral therapy (ART)-induced viral suppression among people with HIV (PWH). Prolonged viral suppression reduces immune dysregulation, reflected by rising CD4+/CD8+ ratios (CD4+/CD8+). We studied CD4+/CD8+ over time to determine whether it predicts risk for select comorbidities and mortality among aging PWH with viral suppression. METHODS: We studied HIV Outpatient Study (HOPS) participants prescribed ART during 2000-2018 who achieved a viral load less than 200 copies/ml on or after 1 January 2000, and remained virally suppressed at least 1 year thereafter. We modeled associations of CD4+/CD8+ with select incident comorbidities and all-cause mortality using Cox regression and controlling for demographic and clinical factors. RESULTS: Of 2480 eligible participants,1145 (46%) were aged less than 40 years, 835 (34%) 40-49 years, and 500 (20%) ≥ 50 years. At baseline, median CD4+/CD8+ was 0.53 (interquartile range: 0.30-0.84) and similar among all age groups (P = 0.18). CD4+/CD8+ values and percentage of participants with CD4+/CD8+ at least 0.70 increased within each age group (P < 0.001 for all). CD4+/CD8+ increase was greatest for PWH aged less than 40 years at baseline. In adjusted models, most recent CD4+/CD8+less than 1.00 and less than 0.70 were independently associated with higher risk of non-AIDS cancer and mortality, respectively. CONCLUSION: Pretreatment immune dysregulation may persist as indicated by CD4+/CD8+ less than 0.70. Persistent viral suppression can improve immune dysregulation over time, reducing comorbidity, and mortality risk. Monitoring CD4+/CD8+ among ART-treated PWH with lower values provide a means to assess for mortality and comorbidity risk.
BACKGROUND: Age blunts CD4+ lymphocyte cell count/μl (CD4+) improvements observed with antiretroviral therapy (ART)-induced viral suppression among people with HIV (PWH). Prolonged viral suppression reduces immune dysregulation, reflected by rising CD4+/CD8+ ratios (CD4+/CD8+). We studied CD4+/CD8+ over time to determine whether it predicts risk for select comorbidities and mortality among aging PWH with viral suppression. METHODS: We studied HIV Outpatient Study (HOPS) participants prescribed ART during 2000-2018 who achieved a viral load less than 200 copies/ml on or after 1 January 2000, and remained virally suppressed at least 1 year thereafter. We modeled associations of CD4+/CD8+ with select incident comorbidities and all-cause mortality using Cox regression and controlling for demographic and clinical factors. RESULTS: Of 2480 eligible participants,1145 (46%) were aged less than 40 years, 835 (34%) 40-49 years, and 500 (20%) ≥ 50 years. At baseline, median CD4+/CD8+ was 0.53 (interquartile range: 0.30-0.84) and similar among all age groups (P = 0.18). CD4+/CD8+ values and percentage of participants with CD4+/CD8+ at least 0.70 increased within each age group (P < 0.001 for all). CD4+/CD8+ increase was greatest for PWH aged less than 40 years at baseline. In adjusted models, most recent CD4+/CD8+less than 1.00 and less than 0.70 were independently associated with higher risk of non-AIDS cancer and mortality, respectively. CONCLUSION: Pretreatment immune dysregulation may persist as indicated by CD4+/CD8+ less than 0.70. Persistent viral suppression can improve immune dysregulation over time, reducing comorbidity, and mortality risk. Monitoring CD4+/CD8+ among ART-treated PWH with lower values provide a means to assess for mortality and comorbidity risk.
Authors: Javier Martínez-Sanz; Raquel Ron; Elena Moreno; Matilde Sánchez-Conde; Alfonso Muriel; Luis Fernando López Cortés; José Ramón Blanco; Juan Antonio Pineda; Álvaro Mena; Sonia Calzado Isbert; Santiago Moreno; Sergio Serrano-Villar Journal: Front Immunol Date: 2022-03-31 Impact factor: 7.561