CD4/CD8 ratio and CD4 nadir predict mortality following non-communicable disease diagnosis in adults living with HIV.

Abstract

Incidence of non-communicable diseases (NCDs) including cardiovascular disease (CVD), cirrhosis, and non-AIDS-defining cancers (NADCs) have been associated with HIV viremia, CD4 cell counts and CD4/CD8 ratio in persons living with HIV. This study examined the importance of these markers to mortality risk following NCD diagnosis.We examined factors associated with mortality following incident CVD, cirrhosis, or NADCs in a clinical cohort of PLWH between 1998-2015.We calculated Kaplan-Meier estimates and used multivariable Cox proportional hazard models.We included 341 patients with NCDs (CVD=169, cancer=103, and cirrhosis=67), of whom 129 died. Median age at NCD diagnosis was 49 years and median proportion of time before NCD with virologic suppression was 64%. Median survival after CVD was longer than for cancer or cirrhosis (11.6 years vs. 4.8 and 3.4 years, respectively; log rank test p<0.001). In multivariable Cox proportional hazards models, higher CD4/CD8 ratio preceding NCD (adjusted hazard ratio [aHR] per 0.1 increase = 0.92 [95% confidence interval 0.85-0.99]) and higher CD4 nadir (aHR per 100 cells/μL = 0.84 [0.72-0.97]) were associated with decreased mortality risk. Neither CD4 cell count prior to NCD nor HIV viremia was statistically associated with mortality in adjusted models. When restricted to 116 patients with virologic suppression for ≥ 80% of time before NCD, only CD4 nadir was associated with mortality risk.Low CD4/CD8 ratio and CD4 nadir were associated with increased mortality risk after NCD, suggesting that prior immunosuppression or ongoing immune imbalance remain important for outcomes following serious NCDs.