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CD4:CD8 Ratio Remains Significantly Depressed Despite Viral Suppression With Effective ART
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Reported by Jules Levin
CROI 2014 March 3-6
Boston, MA
Brinda Emu1, Jeffrey Martin2, Douglas Nixon2, Steven G. Deeks2, Joseph M. McCune2
1Yale University, New Haven, CT, United States, 2University of California, San Francisco, San Francisco, CA, United States
CD4:CD8 ratio was evaluated in HIV-infected subjects with viral loads >10,000 copies/μl ("non-controllers", n=42), those with undetectable viral loads on ART ("ART-suppressed", n=53), and HIV-uninfected subjects (n=22).......We also studied longitudinal changes in ratio in a a subset of 15 individuals who had been on effective therapy for for a median of 3.7 years (1.0 - 6.9) and who had a median CD4+ T cell count of 482 (range 300-1079) and a ratio of 0.44 (range 0.21-1.52).......the majority of individuals showing minimal change in the ratio during this time........Only a minority of individuals demonstrated any further gains in CD4:CD8 ratio with prolonged ARV therapy. A low CD4:CD8 ratio is a biomarker of poor clinical outcomes in the elderly non-HIV infected population, but requires further studies of clinical correlation in HIV-infected individuals" from Jules: and in the CROI poster I just distributed by lead author Sergio Serrano-Villar, subjects with low CD4/CD8 ratio had more serious non-AIDS events, mortality, senescence & activation.
Program Abstract-
Background: Inverted CD4:CD8 ratio is known to be indicative of advanced, untreated HIV infection. In the HIV-uninfected population, a low CD4:CD8 ratio
has also been associated with near-term mortality in the elderly. This study aimed to characterize the CD4:CD8 ratio in untreated and treated HIV-infection,
and to determine the relative dynamics of changes in each population over time during effective ART.CD4:CD8 ratio in HIV-infected individuals on effective
antiretroviral (ARV) regimens.
Methodology: CD4:CD8 ratio was evaluated in HIV-infected subjects with viral loads >10,000 copies/μl ("non-controllers", n=42), those with
undetectable viral loads on ART ("ART-suppressed", n=53), and HIV-uninfected subjects (n=22) from a longitudinal cohort study in San Francisco
(SCOPE). In addition, CD4:CD8 ratio, and T cell phenotypes were evaluated in 25 non-controllers, 18 ART-suppressed, and 7 HIV-uninfected subjects.
Results: CD4:CD8 ratio in non-controllers, ART suppressed, and HIV-uninfected subjects was 0.25, 0.48, and 1.95 respectively (P<0.0001 for all
comparisons). The increased ratio in ART-suppressed compared to non-controllers was driven by an increase of CD4+ T cells, with limited differences in
the expanded CD8+ T cell population. We also studied longitudinal changes in ratio in a a subset of 15 individuals who had been on effective therapy for for
a median of 3.7 years (1.0 - 6.9) and who had a median CD4+ T cell count of 482 (range 300-1079) and a ratio of 0.44 (range 0.21-1.52). With additional
time on ARV (median of 3.1yrs, range 1.3-4.2 yrs), total CD4+ T cell counts increased by 101 cells/mcl (p=0.02) while CD8+ T cells generally remained
stable (p=0.22), resulting in an overall increase in CD4:CD8 ratio from 0.44 to 0.60 (p=0.02). However, the overall gains in CD4:CD8 ratio was driven by
only a few individuals (five of fifteen), with the majority of individuals showing minimal change in the ratio during this time.
Conclusions: Untreated HIV infection is associated with a low CD4:CD8 ratio. Effective therapy improves the ratio, but this improvement is primarily
caused by increases in CD4+ T cell counts. Increases in the ratio are largely due to increased CD4+ T cells, with a persistently expanded CD8+ T cells
limiting further normalization of the ratio. Only a minority of individuals demonstrated any further gains in CD4:CD8 ratio with prolonged ARV therapy. A
low CD4:CD8 ratio is a biomarker of poor clinical outcomes in the elderly non-HIV infected population, but requires further studies of clinical correlation in HIV-infected individuals.
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