Abstract:
Objectives: To assess baseline prevalence of cryptococcal antigen (CrAg) positivity;
and its contribution to reductions in all-cause mortality, deaths from cryptococcus and
unknown causes, and new cryptococcal disease in the REALITY trial.
Design: Retrospective CrAg testing of baseline and week-4 plasma samples in all 1805
African adults/children with CD4þ cell count less than 100 cells/ml starting antiretrovi ral therapy who were randomized to receive 12-week enhanced-prophylaxis (flucona zole 100 mg/day, azithromycin, isoniazid, cotrimoxazole) vs. standard-prophylaxis
(cotrimoxazole).
Methods: Proportional hazards models were used to estimate the relative impact of
enhanced-prophylaxis vs. standard-cotrimoxazole on all, cryptococcal and unknown
deaths, and new cryptococcal disease, through 24 weeks, by baseline CrAg positivity.
Results: Excluding 24 (1.4%) participants with active/prior cryptococcal disease at
enrolment (all treated for cryptococcal disease), 133/1781 (7.5%) participants were
CrAg-positive. By 24 weeks, 105 standard-cotrimoxazole vs. 78 enhanced-prophylaxis
participants died. Of nine standard-cotrimoxazole and three enhanced-prophylaxis
cryptococcal deaths, seven and two, respectively, were CrAg-positive at baseline.
Among deaths of unknown cause, only 1/46 standard-cotrimoxazole and 1/28
enhanced-prophylaxis were CrAg-positive at baseline. There was no evidence that
relative reductions in new cryptococcal disease associated with enhanced-prophylaxis
varied between baseline CrAg-positives [hazard-ratio ¼ 0.36 (95% confidence interval
0.13–0.98), incidence 19.5 vs. 56.5/100 person-years] and CrAg-negatives [hazard ratio ¼ 0.33 (0.03–3.14), incidence 0.3 vs. 0.9/100 person-years; Pheterogeneity¼ 0.95];
nor for all deaths, cryptococcal deaths or unknown deaths.
