EATG » Prednisone cuts risk of dangerous immune-system rebound during HIV-TB treatment

Prednisone cuts risk of dangerous immune-system rebound during HIV-TB treatment

Giving low-dose prednisone soon after initiation of HIV therapy to people who are both infected with tuberculosis and have very low CD4 counts can prevent their immune system from dangerously rebounding against the TB infection, doctors report.

The rebound is known as paradoxical tuberculosis-associated immune reconstruction inflammatory syndrome, or IRIS.

In the new clinical trial, the problem appeared in 32.5% of 120 patients who received prednisone therapy during their first four weeks of antiretroviral therapy for their HIV infection. It affected 46.7% of the 120 who received placebo instead (P=0.03).

The improvement was seen “without evidence of an increased risk of severe infections or cancers,” said the team, led by Dr. Graeme Meintjes of the University of Cape Town in South Africa.

Starting antiretroviral therapy for HIV patients with low CD4 counts, and doing it within the first two weeks of treatment for TB, saves lives, he told Reuters Health by email.

“But this also comes at the cost of a two-fold higher risk of developing a common inflammatory complication – TB-IRIS. Until now, no management strategy existed for preventing this complication. The findings of our study provide clinicians with a strategy for reducing the risk for this complication. There was a 30% reduction in TB-IRIS in patients who received prednisone,” Dr. Meintjes said.

Five volunteers in the prednisone group died versus four who got placebo. The rate of severe infections was lower with prednisone, but not significantly so, occurring in 11 prednisone patients and 18 placebo recipients (P=0.23).

All of the patients had CD4 counts of 100 cells/uL or less. All had started treatment for their TB within 30 days of beginning antiretroviral therapy for their HIV.

In many countries, people are found to have HIV because they are showing symptoms of tuberculosis.

“While TB-IRIS is an infrequent cause of death, many patients can develop quite severe symptoms and around a quarter who develop TB-IRIS require hospitalisation,” said Dr. Meintjes. “The findings of our trial provide a strategy for clinicians to reduce the risk.”

The study, known as PredART, was done at an HIV-TB clinic in the South African township of Khayelitsha. Patients with Kaposi’s sarcoma, rifampin-resistant TB, neurologic or pericardial TB, or other conditions were excluded.

The total daily dose of prednisone was 40 mg for the first 14 days followed by 20 mg for the next 14 days.

When cases of tuberculosis-associated IRIS did appear, they were treated on an open-label basis with 1.5 mg of prednisone per kilogram of body weight per day.

The trial was not powered to detect a mortality benefit of prednisone treatment.

Dr. Meintjes said based on early word of the findings, “there is now a recommendation for the use of prednisone to prevent TB-IRIS in the European AIDS Clinical Society ART guidelines and CDC Opportunistic Infection guidelines.”

“We anticipate the publication of these findings may lead other guideline committees to adopt this recommendation,” he said.

SOURCE: https://bit.ly/2DAwBZy

N Engl J Med 2018.

By Gene Emery


 

Source:
Medscape
News categories: Tuberculosis, Immune response