番茄社区

BOSTON -- Treatment with an integrase inhibitor-based therapy among HIV-infected persons co-infected with tuberculosis appears to be effective, researchers reported here at the Conference on Retroviruses and Opportunistic Infections.

Across a wide group of clinics, 81% of the patients co-infected and under treatment for rifampin-based tuberculosis and HIV achieved virus suppression to undetectable levels using the 50 copies/mL assay, reported Kelly Dooley, MD, PhD, of Johns Hopkins Medicine in Baltimore.

Although the INSPIRING trial was set up as a Phase IIIb, non-comparative, active-control, randomized, open-label study in HIV-infected antiretroviral-naïve adults with drug-sensitive tuberculosis, the researchers also looked at how patients receiving standard-of-care efavirenz-based therapy also fared, Dooley explained at a press briefing. She said that 89% of patients who received efavirenz as part of their combination treatment achieved undetectable HIV viral loads.

Dooley told 番茄社区 that the researchers considered the outcomes to be similar because of the early 24-week look at efficacy and the small numbers of patients in the study. She said there were a few patients who were still on treatment after 24 weeks who had achieved undetectable viral loads, but they were not included in the current analysis.

The primary endpoint of the study was to determine the outcomes at 48 weeks, with assessment of how many patients were cured of their tuberculosis infection also to be performed at the end of the study. "What results we do have indicate an 88-90% success in tuberculosis treatment," she said.

The researchers enrolled 69 patients diagnosed with HIV and tuberculosis and randomly assigned them to receive dolutegravir plus two nucleoside reverse transcriptase inhibitors; 44 patients were treated with the efavirenz plus two nucleoside reverse transcriptase inhibitors.

"Dolutegravir-based regimens are now recommended by the [World Health Organization] as alternative first-line regimens, and several countries with high HIV prevalence have adopted dolutegravir-based regimens as first-line treatment," Dooley said. However, she noted that in healthy volunteers, treatment with rifampin -- a key agent in treated tuberculosis -- reduced the bioavailability of dolutegravir by 72%. The current study sought to determine if increasing the dolutegravir dose from 35 to 50 mg twice daily would overcome the problem of the drug-drug interaction in patients being treated for both diseases.

The researchers reported that 50 of the 69 patients assigned to dolutegravir had an adverse event during the first 24 weeks of the trial -- about 72% of the cohort. About 91% of the patients receiving efavirenz-based therapy reported some adverse event, which represented 40 of the 44 patients in that wing of the study. Drug-related serious adverse events occurred in 1% of each group; two patients in the efavirenz group withdrew due to drug-related adverse events.

Dooley said there were no adverse events that met the stopping criteria for drug-induced liver injury, and none of those liver-related adverse events led to discontinuation from the study. In addition, there were low rates of immune reconstitution inflammatory syndrome in both patient populations, and none of those led to discontinuation.

The patients in the study were approximately 33 years old, and about 40% were women. A total of 67% were of African heritage, and more than half the patients had more than 100,000 copies/mL of HIV RNA; the patients had a median CD4-positive cell counts of more than 300 cells/mm³. Almost all of the patients in both arms of the study were co-diagnosed with pulmonary tuberculosis, and about 70% were treated with a nucleoside reverse transcriptase backbone of tenofovir/emtricitabine.

Asked for her perspective, Constance Benson, MD, director of the Antiviral Research and the HIV/AIDS Clinical Trials Units at the University of California, San Diego, told 番茄社区: "I certainly would feel comfortable using the dolutegravir regimen as was used in this trial. In fact, many of us already are using it. I think it is very important in parts of the world where there are very few other alternatives for treatment of tuberculosis and HIV. Most of the countries where there are high burdens of tuberculosis and HIV do not yet have dolutegravir access, and they will very soon."

Benson added that the current trial will help physicians determine where the dolutegravir-based therapy will fit into the local treatment algorithms once the therapy becomes available.

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