Prednisone attenuates IRIS in people with TB and HIV

Trial suggests use of the steroid with TB treatment reduces risk of complications

SEATTLE — Patients diagnosed with tuberculosis and human immunodeficiency virus (HIV) may avoid development of sometimes fatal complications when treatment is initiated, researchers reported here.

Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS), a consequence of the rapid death of infectious cells at initial treatment, was observed in 46.7% of the 120 patients who were assigned to placebo and 32.5% of the 120 patients who were treated with prednisone (P=0.02), reported Graeme Meintjes, MD, of the University of Cape Town in South Africa.

In a late-breaker presentation at the annual Conference on Retroviruses and Opportunistic Infections, Meintjes said that in patients at high risk of paradoxical TB-IRIS, use of prednisone during the first 4 weeks of antiretroviral therapy reduced the risk of TB-IRIS by 30% (RR=0.70 [95% CI 0.51-0.96]) and further reduced the requirement for corticosteroids to treat TB-IRIS by 53%.

“The intervention was well tolerated with no excess risk of infection or malignancy.”

In more than 90% of patients in each group, HIV viral load was reduced by more than 2log₁₀ at week 12. The median CD4-positive cell counts had risen to 150 or more cells/mm³ at 12 weeks in both groups.

A total of 240 patients were included in the placebo-controlled, double-blind, randomized clinical trial. Tuberculosis was confirmed in 175 of the patients, and 18 other patients withdrew from the trial or were lost to follow-up. Meintjes said 106 patients who were assigned to prednisone completed the 12-week study, and 107 patients on placebo completed the study. Patients were recruited from four public sector HIV-tuberculosis clinics in Khayelitsha, Cape Town, between August 2013 and February 2016.

Patients were treated with prednisone at 40 mg a day for 2 weeks and then 20 mg of prednisone for an additional 2 weeks, or were assigned to receive placebo. Patients were initiated on HIV treatment at the same time they started placebo or prednisone. The average age of the patients was 36, about 60% were men, and the CD4-positive cell count at baseline was about 50 cells/mm³

To be eligible for the study, patients had be antiretroviral-naïve, treated within 30 days of initiation of tuberculosis therapy, and have HIV CD4-positive cells counts of 100 cell/mm³ or less. Patients with rifampicin resistance, neurological tuberculosis, Kaposi’s sarcoma, were positive for Hepatitis B, and not following standard tuberculosis treatment were excluded.

“It is common that people present with symptoms of tuberculosis and are also diagnosed with HIV,” Meintjes said, adding that some of the symptoms of TB-IRIS are severe enough to require hospitalization, and one patient in the placebo group died as the result of TB-IRIS. Nine patients in the placebo group required hospitalization for TB-IRIS compared with five who were receiving prednisone (P=0.41).

Meintjes noted that although he and his colleagues had been concerned that treatment with prednisone would increase the risk of infection, 15.1% of the placebo patients developed new AIDS-defining infection or invasive bacterial infections compared with 9.2% of the patients on placebo (P=0.17). Overall, 27 patients on placebo and 24 on prednisone had Grade 3 or 4 adverse events.

Constance Benson, MD, of the University of California at San Diego, told MedPage Today, “We see that the use of prednisone is preemptive treatment for a serious complication of antiretroviral therapy combined with HIV therapy in a segment of the HIV-infected individuals. This was a very nicely done randomized clinical trial that gives ample evidence for preemptive therapy with prednisone, and this is not an expensive drug. In the short-term, there did not seem to be any undue complications to prednisone therapy.

“If I were in an area where there is a high risk of TB-IRIS and you are treating a population with very low CD4 counts and TB, this would be enough evidence for me to change my practice,” said Benson, who was not involved in the study. “We did discuss that the dose of prednisone used in this study might have been too low, and that a higher dose of the steroid might be necessary and might give even more benefit.”

Benson added that because the drugs used in treatment of tuberculosis can interact with prednisone and reduce its effectiveness, a higher dose of prednisone should be studied.