CD4:CD8 ratio recovery reduces with higher age when starting ART

A longitudinal cohort study published in the 28 November issue of AIDS reports decreased CD4:CD8 recovery levels relative to age at time of ART initiation. [1]

A lower CD4:CD8 ratio is a marker of reduced immune function and immune activation and values >1.0 are considered normal. Across all participants, median (IQR) ratios increased significantly from 0.24 (0.24 to 0.38) to 0.88 (0.64 to 1.17) after 10 years on ART. However, there was no age group in which the majority of people had CD4:CD8 ratio >1 after 10 years.

The cohort enrolled 1859 people age 20 to 78 who were living with HIV and who accessed HIV care at the Royal Free Hospital in London between 2001 and 2015. Within the study period there were two major HIV epidemics: one for gay and bisexual men and a second amongst Black heterosexual men and women.

Study participants were female (25%), Black (29%) and Asian (6%). Baseline age was split into the following deciles: 20 to 29 (n=235), 30 to 39 (n=748), 40 to 49 (n=597), 50 to 59 (n=221), 60 to 69 (n=49) and 70 to 79 (n=9). Data were adjusted for baseline CD4 count, year of ART initiation, ethnicity and gender.

Overall, median (IQR) CD4 counts increased from a baseline of 256 cells/mm³ (132 to 375) to 668 cells/mm³ (511 to 837) at year 10. Median (IQR) CD4:CD8 ratios followed a similar trend with a net increase from 0.24 (0.24 to 0.38) to 0.88 (0.64 to 1.17) across the 10-year period.

Median (IQR) ratios at 10 years by age decile were as follows: 0.95 (0.75 to 1.29: 20 to 29 years), 0.92 (0.71 to 1.2: 30 to 39 years), 0.84 (0.61 to 1.09: 40 to 49 years), 0.80 (0.56 to 1.24: 50 to 59 years), 0.57 (0.46 to 0.86: 60 to 69 years) and 0.57 (0.52 to 0.60: 70 to 79 years).

There was a positive correlation between age at ART initiation and 10-year mortality. Total mortality was 1.7% for those aged under 60 and rose to 8.2% for those over 60, and 22% (2/9 participants) for the over 70s.

Older age was associated with slower ratio recovery and lower ratios at years 5 and 10 of follow-up. It should also be noted that the study only included people who achieved viral suppression within six months of ART initiation, and the group sizes for the oldest deciles were small.

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These results are important for quantifying the impact associated with the later use of ART and the importance of earlier diagnosis.

At least part of the explanation for lower numbers of people reaching a CD4:CD8 ratio >1.0 will be linked to years when ART was only recommended at a lower absolute CD4 count.

Since 2015, earlier use of ART has been recommended at any CD4 count thanks to results from the START study. [2]