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CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy: an observational cohort study
Published by Pedro CAHN

Updated: 1 May, 2015

Mussini C et al. Lancet HIV 2015; Volume 2, No. 3, e98–e106, March 2015

In patients with HIV, immune reconstitution on antiretroviral therapy is often incomplete. This study assessed the probability of patients to reach a CD4/CD8 ratio ≥ 1 after the start of antiretroviral therapy and its association with the onset of non-AIDS-defining events and death. The analysis was done in the ICONA cohort, which recruited treatment-naive patients with HIV in Italy. Participants from the cohort were included in the analysis if they reached an undetectable viral load (≤ 80 copies/mL), and had a CD4/CD8 ratio < 0.8 at the time of an undetectable viral load. CD4/CD8 ratio normalisation was defined as two consecutive values ≥ 1. Kaplan-Meier curves were used to estimate the cumulative probability of ratio normalisation. Poisson regression models were used to identify factors independently associated with normalisation and with progression to non-AIDS-defining events or death. Between January 22, 1997 and February 25, 2013, 3,236 participants were enrolled. At the start of antiretroviral therapy, median CD4/CD8 ratio was 0.39 (range 0.26-0.55). 458 (14%) patients reached a CD4/CD8 ratio ≥ 1. The estimated probability of normalisation was 4.4% (95%, CI = 3.7-5.2) by 1 year from baseline, 11.5% (10.2-13.0) by 2 years, and 29.4% (26.7-32.4) by 5 years. Factors associated with normalisation were high pre-ART CD4 cell counts, a high CD4/CD8 ratio at baseline, and negative CMV serological findings. The incidence rate of non-AIDS-defining events for patients with a CD4/CD8 ratio < 0.30 (4.2 per 100 patient years, 95% CI = 3.4-5.3) was double that for those with a ratio of 0.30-0.45 (2.3, 2.1-2.5) or > 0.45 (2.2, 1.7-2.9). A ratio < 0.30 was independently associated with an increased risk of non-AIDS-defining events or death compared with one > 0.45. In conclusion, few patients normalised CD4/CD8 ratio on antiretroviral therapy, even though they had viral suppression. Low CD4/CD8 ratios were associated with increased risk of serious events and deaths. The CD4/CD8 ratio could be used by clinicians to identity patients at risk of non-AIDS-related events.