Background In patients with HIV, immune reconstitution after antiretroviral therapy (ART) is often incomplete. We assessed the probability of patients reaching a CD4/CD8 ratio of 1 or more after the start of ART and its association with the onset of non-AIDS-defi ning events and death.Methods We did an analysis of the ICONA cohort, which recruited treatment-naive patients with HIV in Italy. We included participants in the cohort who started ART, reached an undetectable viral load (<= 80 copies per mL), and had a CD4/CD8 ratio of less than 0.8 at the time of an undetectable viral load. We defined ratio normalisation in patients as two consecutive values of 1 or more. We used Kaplan-Meier curves to estimate the cumulative probability of ratio normalisation. We then used Poisson regression models to identify factors independently associated with normalisation and with progression to non-AIDS-defi ning events or death.Findings We included 3236 participants, enrolled between Jan 22, 1997, and Feb 25, 2013. At the start of ART, median CD4/CD8 ratio in our population was 0.39 (IQR 0.26-0.55). 458 (14%) patients reached a CD4/CD8 ratio of 1 or more; 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 cytomegalovirus serological findings. The incidence rate of non-AIDS-defi ning events for patients with a CD4/CD8 ratio of less than 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 more than 0.45 (2.2, 1.7-2.9). A ratio of less than 0.30 was independently associated with an increased risk of non-AIDS-defi ning events or death compared with one of more than 0.45.Interpretation Few patients had normalised CD4/CD8 ratios, even though they had viral suppression. Low 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.
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
Lo Caputo Sergio
2015-01-01
Abstract
Background In patients with HIV, immune reconstitution after antiretroviral therapy (ART) is often incomplete. We assessed the probability of patients reaching a CD4/CD8 ratio of 1 or more after the start of ART and its association with the onset of non-AIDS-defi ning events and death.Methods We did an analysis of the ICONA cohort, which recruited treatment-naive patients with HIV in Italy. We included participants in the cohort who started ART, reached an undetectable viral load (<= 80 copies per mL), and had a CD4/CD8 ratio of less than 0.8 at the time of an undetectable viral load. We defined ratio normalisation in patients as two consecutive values of 1 or more. We used Kaplan-Meier curves to estimate the cumulative probability of ratio normalisation. We then used Poisson regression models to identify factors independently associated with normalisation and with progression to non-AIDS-defi ning events or death.Findings We included 3236 participants, enrolled between Jan 22, 1997, and Feb 25, 2013. At the start of ART, median CD4/CD8 ratio in our population was 0.39 (IQR 0.26-0.55). 458 (14%) patients reached a CD4/CD8 ratio of 1 or more; 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 cytomegalovirus serological findings. The incidence rate of non-AIDS-defi ning events for patients with a CD4/CD8 ratio of less than 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 more than 0.45 (2.2, 1.7-2.9). A ratio of less than 0.30 was independently associated with an increased risk of non-AIDS-defi ning events or death compared with one of more than 0.45.Interpretation Few patients had normalised CD4/CD8 ratios, even though they had viral suppression. Low 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
