Determinants of restoration of CD4 and CD8 cell counts and their ratio in HIV-1 positive individuals with sustained virological suppression on antiretroviral therapy

Journal article

Background: An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV uninfected individuals more likely and whether restoration depends on gender, age and other individual characteristics. Methods: We determined median and quartile reference values for CD4 and CD8 cell count and their ratio using cross-sectional data from 2,309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed effects models. Results: When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first two years median CD8 cell counts converged towards median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with <250 CD4 cells/mm3. Median CD4:CD8 trajectories did not reach median reference values, even when ART was started at 500 cells/mm3. Discussion: Starting ART with a CD4 cell count of ≥500 cells/mm3 makes reaching median reference CD4 cell counts more likely. However, median CD4:CD8 ratio trajectories remained below the median levels of HIV-negative individuals, because of persisting high CD8 cell counts. To what extent these subnormal immunological responses have impact on specific clinical endpoints requires further investigation.

Authors: Gras, L; May, M; Ryder, L; Trickey, A; Helleberg, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wolters Kluwer
• Journal: Journal of Acquired Immune Deficiency Syndromes
• Volume: 80
• Issue: 3
• Pages: 292-300
• Publication date: 2018-10-15
• Acceptance date: 2018-10-15
• DOI: 10.1097/qai.0000000000001913
• EISSN: 1944-7884
• ISSN: 1525-4135
• Pmid: 30531492
• Language: English
• Keywords: CD4 cell count; age; HIV; CD4:CD8 ratio; antiretroviral therapy; CD8 cell count