Administering prednisone during the first month of antiretroviral therapy (ART) for those with HIV leads to a lower incidence of tuberculosis-related immune reconstitution inflammatory syndrome, according to a study recently published in The New England Journal of Medicine. This treatment is not associated with a higher risk for cancer or acute infection.
This double-blind, randomized study (trial number NCT01924286 at ClinicalTrials.gov) included 240 participants with HIV who were beginning ART for the first time. Of these, 73% were diagnosed with tuberculosis at baseline, and the group had a median HIV-1 RNA viral load of 5.5 log10 copies/mL and a median CD4 count of 49 cells/µL. The group was randomly assigned 1:1 to either once-daily prednisone (40 mg/day for 2 weeks, then 20 mg/day for 2 weeks) or to placebo.
Over 84 days, tuberculosis-related immune reconstitution inflammatory syndrome was significantly lower among the prednisone group than the placebo group (32.5% vs 46.7%; relative risk [RR] 0.70; 95% CI, 0.51-0.96; P =.03). Those diagnosed with tuberculosis-related immune reconstitution inflammatory syndrome in the 2 groups showed a similar length of time to first symptoms (10 days vs 8 days for prednisone vs placebo, respectively).
The prednisone group presented with fewer grade-3 clinical adverse events than the placebo group, but grade-4 events showed no significant difference, nor did laboratory adverse events of grades 3 or 4. In the prednisone group, open-label glucocorticoids were administered to 16 patients as treatment for tuberculosis-related immune reconstitution inflammatory syndrome and to 34 in the placebo group (RR 0.47; 95% CI, 0.27-0.81). The prednisone group experienced 5 deaths, whereas the placebo group experienced 4 (P =1.00), and 11 and 18 patients experienced acute infections in the groups, respectively (P =.23).
Participants in this study had a median age of 36 years, and 60% were men. Inclusion criteria included initiation of tuberculosis treatment within 30 days after the start of ART and CD4 counts of <100 cells/µL. The study’s primary endpoint was a confirmed diagnosis of tuberculosis-related immune reconstitution inflammatory syndrome within 12 weeks after initiation of ART.
The study researchers concluded that “among adult [patients with] HIV receiving anti-tuberculosis treatment who were at high risk for tuberculosis-associated immune reconstitution inflammatory syndrome, the incidence of tuberculosis-associated immune reconstitution inflammatory syndrome was lower among those who received a 4-week course of prednisone, prescribed when ART was started, than among those who received placebo.”
Meintjes G, Stek C, Blumenthal L, et al. Prednisone for the prevention of paradoxical tuberculosis-associated IRIS. N Engl J Med. 2018;379(20):1915-1925. doi: 10.1056/NEJMoa1800762.