Despite effective antiretroviral therapy (ART), people living with HIV (PLWH) still experience excess morbidity and mortality, with a growing awareness of the impact of non-AIDS defining events (NADE) and the factors potentially associated with the occurrence of these events including failure to normalise the CD4:CD8 ratio.
Adult PLWH enrolled in the Mater ID Cohort Study who commenced ART after January 1st 2001 were included in an analysis determining prevalence of and associations with AIDS events and NADE. Demographic, laboratory (including HIV RNA, CD4+ and CD8+ T-cell counts, CD4:CD8 ratio) and clinical events (AIDS and NADE) were collated. Multivariable Cox proportional hazards regression models explored factors independently associated with the progression to NADE. Data are reported as median (IQR).
Of 550 PLWH, 317 (58%) were male, 299 (54%) Caucasian, 220 (40%) African, 114 (21%) Men who have sex with Men and 131 (24%) Injecting drug users (IDU). 128 (23%) were co-infected with Hepatitis C. At ART initiation median age was 34 (29, 40) yrs, and nadir CD4+ count 187 (80, 284) cells/mm3. Of 135 NADE in 2557 person years of follow (crude incidence 5.3 per 100 PYFU), the commonest were pneumonia (n=39), liver disease (n=17), cardiovascular disease (CVD) (n=14) and non AIDS malignancies (n=12). Of 23 deaths, 5 were AIDS related and 11 were NADE (malignancy (n=7), liver disease (n=2), CVD (stroke) (n=1), abdominal sepsis (n=1)). In multivariable Cox models, older age at ART initiation, IDU risk and lower quintiles of pre-event CD4:CD8 ratio were independently associated with an increased risk of non-AIDS defining events (see figure 1), with male gender and non-Caucasian ethnicity independently associated with reduced risk of NADE (see figure 1). A sensitivity analysis in those virally suppressed revealed similar associations with age at ART initiation (HR=1.59, 95% CI 1.23-2.05), gender (HR=0.33, 95% CI 0.20-0.56) and lower pre-event CD4:CD8 ratio (CD4:CD8 ratio≤0.26; HR=3.11 (95% CI 1.44-6.71),CD4:CD8 ratio 0.27-0.43; HR=1.64 (95% CI 0.74—3.66), CD4:CD8 ratio 0.44-0.59; HR= 1.67 (95% CI 0.77-3.66), CD4:CD8 ratio 0.60-0.86; HR=1.26 (95% CI 0.54-2.93)).
This is the first study to show an incremental association between pre-event CD4:CD8 ratio and NADE. It is yet to be determined what impact, if any, strategies to improve CD4:CD8 ratio will have on prevalence of NADE.