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Aging, trends in CD4+/CD8+ cell ratio, and clinical outcomes with persistent HIV suppression in a dynamic cohort of ambulatory HIV patients
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Novak, Richard M.a; Armon, Carlb; Battalora, Lindab,c; Buchacz, Kated; Li, Jund; Ward, Douglase; Carlson, Kimberlyb; Palella, Frank J. Jrf
AIDS May 2022
"Our findings indicate that there are effects consequent to both aging and the degree of baseline immune dysregulation that influence long-term ability to recover immune function, even after years of viral suppression, and appear to have clinical consequences extending to non-HIV comorbidities and mortality. Persistent viral suppression does lead to improvements in immune dysregulation over time, as measured by changes in CD4+/CD8+, which appear to diminish the risk of comorbidities and mortality. Monitoring CD4+/CD8+ amongvirally suppressed ART-treated PWH with lower CD4+/CD8+ provide a means to assess for mortality and comorbidity risk."
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.
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