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. 2022 May 1;36(6):815-827.
doi: 10.1097/QAD.0000000000003171. Epub 2022 Jan 10.

Aging, trends in CD4+/CD8+ cell ratio, and clinical outcomes with persistent HIV suppression in a dynamic cohort of ambulatory HIV patients

Richard M Novak  1 , Carl Armon  2 , Linda Battalora  2   3 , Kate Buchacz  4 , Jun Li  4 , Douglas Ward  5 , Kimberly Carlson  2 , Frank J Palella Jr  6 ; HIV Outpatient Study (HOPS) Investigators
Affiliations

Aging, trends in CD4+/CD8+ cell ratio, and clinical outcomes with persistent HIV suppression in a dynamic cohort of ambulatory HIV patients

Richard M Novak et al. AIDS. .

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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Conflict of interest statement

Conflicts of interest

F.J.P. has been a consultant and/or on the Speakers’ Bureau for Gilead Sciences, Janssen Pharmaceuticals, Merck and Co., and ViiV. R.M.N. is a consultant to ViiV and Gilead Sciences.

Figures

Fig. 1.
Fig. 1.. Selection steps flowchart of patients included in the current analysis, the HIV Outpatient Study 2000–2018, N = 2480.
Fig. 2.
Fig. 2.. (a) Median CD4+/CD8+ by baseline age group and year of follow-up, the HIV Outpatient Study, 2000–2018, N = 2480.
*Jonckheere~Terpstra test of trend. IQR, interquartile range. (b) Percentage of participants with CD4+/CD8+ at least 0.70 by baseline age group and year of follow-up, the HIV Outpatient Study, 2000–2018, N = 2480. *Cochran–Armitage test of trend. (c) Percentage of participants with CD4+/CD8+ less than 0.70 by baseline age group and year of follow-up, the HIV Outpatient Study, 2000–2018, N = 2480. *Cochran–Armitage test of trend.
Fig. 2.
Fig. 2.. (a) Median CD4+/CD8+ by baseline age group and year of follow-up, the HIV Outpatient Study, 2000–2018, N = 2480.
*Jonckheere~Terpstra test of trend. IQR, interquartile range. (b) Percentage of participants with CD4+/CD8+ at least 0.70 by baseline age group and year of follow-up, the HIV Outpatient Study, 2000–2018, N = 2480. *Cochran–Armitage test of trend. (c) Percentage of participants with CD4+/CD8+ less than 0.70 by baseline age group and year of follow-up, the HIV Outpatient Study, 2000–2018, N = 2480. *Cochran–Armitage test of trend.
Fig. 2.
Fig. 2.. (a) Median CD4+/CD8+ by baseline age group and year of follow-up, the HIV Outpatient Study, 2000–2018, N = 2480.
*Jonckheere~Terpstra test of trend. IQR, interquartile range. (b) Percentage of participants with CD4+/CD8+ at least 0.70 by baseline age group and year of follow-up, the HIV Outpatient Study, 2000–2018, N = 2480. *Cochran–Armitage test of trend. (c) Percentage of participants with CD4+/CD8+ less than 0.70 by baseline age group and year of follow-up, the HIV Outpatient Study, 2000–2018, N = 2480. *Cochran–Armitage test of trend.
Fig. 3.
Fig. 3.. (a) Median CD4+/CD8+ by baseline CD4+/CD8+ range and year of follow-up, the HIV Outpatient Study, 2000–2018, N = 2480.
*Jonckheere-Terpstra test of trend. IQR, interquartile range. (b) Percentage of participants with CD4+/CD8+ at least 0.70 by baseline CD4+/CD8+ range and year of follow-up, the HIV Outpatient Study, 2000–2018, N = 2480. *Cochran-Armitage test of trend.
Fig. 3.
Fig. 3.. (a) Median CD4+/CD8+ by baseline CD4+/CD8+ range and year of follow-up, the HIV Outpatient Study, 2000–2018, N = 2480.
*Jonckheere-Terpstra test of trend. IQR, interquartile range. (b) Percentage of participants with CD4+/CD8+ at least 0.70 by baseline CD4+/CD8+ range and year of follow-up, the HIV Outpatient Study, 2000–2018, N = 2480. *Cochran-Armitage test of trend.
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