Aging, trends in CD4/CD8 ratio and clinical outcomes with persistent HIV suppression in the HIV outpatient study (HOPS).

Age blunts CD4+ lymphocyte cell count/mm3 (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.We studied HIV Outpatient Study (HOPS) participants prescribed ART during 2000-2018 who achieved a VL < 200 copies/mL on or after January 1, 2000, and remained virally suppressed at least one 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.Of 2,480 eligible participants,1,145 (46%) were aged < 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 percent of participants with CD4/CD8 ≥ 0.70 increased within each age group (P < 0.001 for all). CD4/CD8 increase was greatest for PWH aged < 40 years at baseline. In adjusted models, most recent CD4/CD8 < 1.00 and < 0.70 were independently associated with higher risk of non-AIDS cancer and mortality, respectively.Pre-treatment immune dysregulation may persist as indicated by CD4/CD8 < 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 co-morbidity risk.