Long-term trends in CD4 cell counts, CD8 cell counts, and the CD4: CD8 ratio: ART Cohort Collaboration (ART-CC) Study. AIDS
HIV infection leads to persistent immune activation and inflammation, which may accelerate deterioration of the immune system due to ageing (so called “immunosenescence”). In the general population, a low CD4+:CD8+ ratio is a surrogate marker for immunosenescence and an independent predictor of all-cause mortality. Among HIV-positive individuals, low CD4+:CD8+ ratio has been associated with higher levels of immunosenescence and inflammation, although the results regarding whether a low or inverted CD4+:CD8+ ratio predicts non-AIDS-related morbidity and mortality have been conflicting.
In the current work, Hughes et al. on behalf of the ART Cohort Collaboration aimed to quantify long-term trends in CD8+ cell counts and CD4+:CD8+ ratios, up to 15 years after starting antiretroviral therapy (ART), in a large cohort of antiretroviral-naïve individuals starting ART, and assess the impact of baseline CD4+ cell count on these trends.
Eligible patients from the ART Cohort Collaboration were antiretroviral-naïve, started ART after 1997, had at least one CD4+ and CD8+ measurement within the baseline period and one or moreCD4+ and CD8+ measurements 6 months after starting ART.
A total of 39’979 patients were included (median follow-up was 53 months). Among patients with baseline CD4+ cell count at least 50 cells/ml, predicted mean CD8+ cell counts continued to decrease between 3 and 15 years post-ART, partly driving increases in the predicted mean CD4+:CD8+ ratio. During 15 years of follow-up, normalization of the predicted mean CD4+:CD8+ ratio (to >1) was only observed among patients with baseline CD4+ cell count at least 200 cells/ml. A higher baseline CD4+ cell count predicted a shorter time to normalization.
In conclusion, there are long-term decreases in CD8+ cell counts and long-term increases in CD4+:CD8+ ratios, among patients who start ART with CD4+ cell count as low as 50–199 cells/ml. However, starting ART at high CD4+ cell counts is paramount for attainment of a maximal CD4+:CD8+ ratio.