Factors Affecting Timing of Antiretroviral Treatment Initiation Based on Monitoring CD4 Counts

Abstract

To evaluate factors affecting antiretroviral therapy (ART) start time when triggered by a CD4 count <350 cells/μL while monitoring counts over time. Measurement frequency, requirement for confirmatory counts, and precision and accuracy of CD4 enumeration technology were considered. Using a model of CD4 count trajectories among seroconverters in the Multicenter AIDS Cohort Study, sequences of counts were simulated for a large hypothetical population monitored for 5 years from seroconversion. Time of first count <350 cells/μL was defined as ART start time. The simulation was adapted to evaluate the effect of the above factors on these times. ART initiation was considered "very late" among patients whose underlying trajectory declined less than 200 cells/μL during the period simulated if no previous observed count was <350 cells/μL. For 12-, 6-, 4-, and 3-monthly measurements, median start time was 48, 36, 32, and 30 months after seroconversion and proportion of patients starting ART very late was 11.5%, 1.6%, 0.2%, and 0.1%. For 6-monthly measurements, requiring confirmation increased the median to 49 months and proportion to 8.9%. Changes in standard deviation of short-term variability in counts of 25% and measurement bias for a novel technology of ±10% changed median time by ±6 months with modest change in the proportion very late (range, 0.5%-3.2%). : 6-monthly measurements appear adequate in achieving low rates of very late ART whereas confirmation affects rates adversely. Studies comparing new versus standard measurement technologies should focus on ruling out modest bias, particularly proximal to important thresholds for treatment management.