BOSTON — Adding raltegravir to standard-of-care ART did not impact the incidence or case fatality of immune reconstitution inflammatory syndrome, or IRIS, in patients with advanced HIV, according to study results presented at CROI.
Diana M. Gibb, MD, professor of epidemiology and a program leader in the MRC clinical trials unit at University College London, summarized new findings from the Reduction of Early Mortality in HIV-infected Adults and Children Starting Antiretroviral Therapy (REALITY) trial, which is being conducted in Kenya, Malawi, Uganda and Zimbabwe. The trial explores ways to reduce early mortality among adults and older children with advanced HIV who are starting ART for the first time. Currently, around 10% of severely immunosuppressed patients in sub-Saharan Africa die within 3 months of initiating ART.
IRIS is an exaggerated or atypical presentation of an opportunistic infection — sometimes on a tumor — that occurs in patients soon after the initiation of ART, according to Gibb. She said it is thought to occur particularly if a patient’s CD4 count increases quickly or their viral load decreases quickly.
Previous data suggested that the rate of IRIS events might be higher in patients who are given an integrase inhibitor like raltegravir as first-line treatment, especially when they have very low CD4 counts. But Gibb said results from the REALITY trial — which she said could be applied to all integrase inhibitors, including dolutegravir — show the relationship does not exist.
“Basically, the increase in IRIS is not there with integrase inhibitors,” she said during a news conference. “In other words, they are safe to use on a global level.”
Raltegravir did not influence IRIS, but another REALITY intervention did. Results from the trial published last year in The New England Journal of Medicine showed that a low-cost enhanced antimicrobial prophylaxis package with antituberculosis, antibacterial and antifungal elements not only reduced the rate of death by 27% after 24 weeks compared with standard prophylaxis, but also significantly reduced IRIS events.
For the current study, Gibb and colleagues explored giving study participants additional raltegravir on top of non-nucleoside reverse-transcriptase inhibitor-based standard-of-care ART. They randomly assigned 1,805 adults and children aged 5 years and older with CD4 counts under 100 to receive ART with or without raltegravir for the first 12 weeks.
According to Gibb, there was a fast drop in viral load among the study group receiving raltegravir, but this did not impact subsequent mortality or disease progression at 24 or 48 weeks of follow-up. There was no increase in IRIS, with fatal or nonfatal IRIS-compatible events occurring in 9.9% of patients in the study group compared with 9.5% of patients receiving standard ART.
“Integrase inhibitors are first-line therapy in the developed world and increasingly first-line around the world,” said Diane Havlir, MD, professor of medicine at the University of California, San Francisco, who was not involved in the study. “When we left CROI last year, there were some data that had suggested that [IRIS] might be higher in this class of drugs, and that would concern us. So, we’re really delighted that this year we have some data from a randomized trial that asks the question about this relationship.” – by Gerard Gallagher
Editor’s note: In the United States, dolutegravir is sold under the brand name Tivicay (ViiV Healthcare) and raltegravir is sold under the brand name Isentress (Merck).
Gibb D, et al. Abstract 23. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2018; Boston.