Predictors of immune recovery and the association with late mortality while on antiretroviral treatment in Cambodia

The objectives of this study were to examine the association of the on-treatment CD4 cell count with late mortality (after >6 months of antiretroviral treatment [ART]) and to identify the determinants of the long-term CD4 cell count evolution after treatment initiation. We conducted a retrospective analysis including all antiretroviral (ARV)-naive adults initiating ART in a tertiary hospital in Phnom Penh, Cambodia from 2003-2010. We used Cox proportional hazards modelling (mortality analysis), including time-updated CD4 counts, and mixed-effects modelling (CD4 response over time). Overall, 2840 patients were included (47% male, median age: 34 years, median baseline CD4 count: 78 cells/muL). The median time on ART was 2.5 years (IQR 1.1-4.3); 71 patients died after >6 months of ART. The baseline CD4 count was the main determinant of the on-treatment CD4 cell count. Time-updated CD4 cell counts was the strongest determinant of late mortality with a HR of 0.32 (95% CI 0.16-0.63) and 0.29 (95% CI 0.11-0.71) for CD4 values of 200-350 cells/muL and 350-500 cells/muL respectively. We conclude that baseline CD4 counts strongly determine the long-term immune recovery, which critically affects late mortality. This calls for increased efforts for early ART initiation and availability of CD4 count testing in low-income countries.