Dolutegravir-based regimen effective in HIV/TB coinfected

 

BOSTON – In antiretroviral therapy–naive patients with HIV and tuberculosis coinfection, a combination of dolutegravir-based ART and rifampin-based TB therapy was associated with good efficacy and immunological responses through at least 24 weeks, investigators reported.

Dolutegravir-based ART appeared to be comparable to efavirenz-based therapy at viral suppression with a similar safety profile, although the trial was not powered for head-to-head comparison, said Kelly Dooley, MD, of Johns Hopkins University, Baltimore.

“We know that rifampin reduces concentrations of dolutegravir substantially, but that drug interaction can be mitigated by increasing the dose of dolutegravir to twice daily. That information was from a healthy volunteer trial, so we thought it would be important to test HIV/TB cotreatment among patients who have both infections,” she said at the Conference on Retroviruses and Opportunistic Infections.

Dr. Dooley and her colleagues looked at dolutegravir or efavirenz plus rifampin-based TB therapy in the INSPIRING trial.

 

The ongoing study is a phase 3b, noncomparative, randomized, open-label trial in ART-naive adults with HIV-1 and drug-sensitive TB infections.

In a briefing following her presentation of the data in an oral session, Dr. Dooley explained that the reason for the parallel but noncomparative arms in the trial was that it was primarily designed to see how dolutegravir works in HIV/TB coinfected patients. Enrollment of 113 patients from 37 sites in seven countries took about 2 years, and it would have required significantly more time to enroll the more than 500 patients necessary for an adequately powered comparison trial.

The trial was conducted in Argentina, Brazil, Mexico, Peru, Russia, South Africa, and Thailand. Dr. Dooley presented results from a 24-week interim analysis.

Participants who were on rifampin-based TB therapy for up to 8 weeks were randomized on a 3:2 basis to receive either dolutegravir 50 mg twice daily during and for 2 weeks post-TB therapy, followed by 50 mg once daily (69 patients), or efavirenz 600 mg daily plus two nucleoside reverse transcriptase inhibitors of the investigator’s choice for 52 weeks.

 

At 24 weeks, the percentage of patients deemed to have virologic success, defined as HIV-1 RNA less than 50 copies/mL, was 81% in the dolutegravir arm and 89% in the efavirenz arm. The respective rates of virologic nonresponse were 10% and 7%. No virologic data were available because of treatment discontinuations or missing information for 9% and 5% of patients, respectively.

The difference in response rates between the arms was due to non–treatment associated withdrawals among patients on dolutegravir, Dr. Dooley said.

Virologic withdrawals for confirmed plasma HIV-1 RNA of 400 copies/mL or more at or after week 24 for two consecutive tests occurred in one patient on dolutegravir and in none on efavirenz. There were no treatment-emergent resistance-associated mutations to any anti-HIV drugs in the dolutegravir group (data not available for the efavirenz group).

Two patients, both in the efavirenz arm, discontinued therapy because of adverse events. TB-associated rates of the immune reconstitution inflammatory syndrome (IRIS) occurred in 4% of patients in each treatment arm. No patients discontinued therapy because of IRIS or liver-related adverse events.

“We think that this study provides evidence that dolutegravir is effective and well tolerated in adults with HIV/TB coinfection who are receiving rifampin-based tuberculosis therapy, and we hope that this will increase the number of options for TB/HIV coinfected patients for whom there are relatively few treatment possibilities,” she concluded.

Dr. Dooley reported research support via her university from ViiV Healthcare, which funded the study.

[email protected]

SOURCE: Dooley K et al. Abstract 33.

 

BOSTON – In antiretroviral therapy–naive patients with HIV and tuberculosis coinfection, a combination of dolutegravir-based ART and rifampin-based TB therapy was associated with good efficacy and immunological responses through at least 24 weeks, investigators reported.

Dolutegravir-based ART appeared to be comparable to efavirenz-based therapy at viral suppression with a similar safety profile, although the trial was not powered for head-to-head comparison, said Kelly Dooley, MD, of Johns Hopkins University, Baltimore.

“We know that rifampin reduces concentrations of dolutegravir substantially, but that drug interaction can be mitigated by increasing the dose of dolutegravir to twice daily. That information was from a healthy volunteer trial, so we thought it would be important to test HIV/TB cotreatment among patients who have both infections,” she said at the Conference on Retroviruses and Opportunistic Infections.

Dr. Dooley and her colleagues looked at dolutegravir or efavirenz plus rifampin-based TB therapy in the INSPIRING trial.

 

The ongoing study is a phase 3b, noncomparative, randomized, open-label trial in ART-naive adults with HIV-1 and drug-sensitive TB infections.

In a briefing following her presentation of the data in an oral session, Dr. Dooley explained that the reason for the parallel but noncomparative arms in the trial was that it was primarily designed to see how dolutegravir works in HIV/TB coinfected patients. Enrollment of 113 patients from 37 sites in seven countries took about 2 years, and it would have required significantly more time to enroll the more than 500 patients necessary for an adequately powered comparison trial.

The trial was conducted in Argentina, Brazil, Mexico, Peru, Russia, South Africa, and Thailand. Dr. Dooley presented results from a 24-week interim analysis.

Participants who were on rifampin-based TB therapy for up to 8 weeks were randomized on a 3:2 basis to receive either dolutegravir 50 mg twice daily during and for 2 weeks post-TB therapy, followed by 50 mg once daily (69 patients), or efavirenz 600 mg daily plus two nucleoside reverse transcriptase inhibitors of the investigator’s choice for 52 weeks.

 

At 24 weeks, the percentage of patients deemed to have virologic success, defined as HIV-1 RNA less than 50 copies/mL, was 81% in the dolutegravir arm and 89% in the efavirenz arm. The respective rates of virologic nonresponse were 10% and 7%. No virologic data were available because of treatment discontinuations or missing information for 9% and 5% of patients, respectively.

The difference in response rates between the arms was due to non–treatment associated withdrawals among patients on dolutegravir, Dr. Dooley said.

Virologic withdrawals for confirmed plasma HIV-1 RNA of 400 copies/mL or more at or after week 24 for two consecutive tests occurred in one patient on dolutegravir and in none on efavirenz. There were no treatment-emergent resistance-associated mutations to any anti-HIV drugs in the dolutegravir group (data not available for the efavirenz group).

Two patients, both in the efavirenz arm, discontinued therapy because of adverse events. TB-associated rates of the immune reconstitution inflammatory syndrome (IRIS) occurred in 4% of patients in each treatment arm. No patients discontinued therapy because of IRIS or liver-related adverse events.

“We think that this study provides evidence that dolutegravir is effective and well tolerated in adults with HIV/TB coinfection who are receiving rifampin-based tuberculosis therapy, and we hope that this will increase the number of options for TB/HIV coinfected patients for whom there are relatively few treatment possibilities,” she concluded.

Dr. Dooley reported research support via her university from ViiV Healthcare, which funded the study.

[email protected]

SOURCE: Dooley K et al. Abstract 33.

 

BOSTON – In antiretroviral therapy–naive patients with HIV and tuberculosis coinfection, a combination of dolutegravir-based ART and rifampin-based TB therapy was associated with good efficacy and immunological responses through at least 24 weeks, investigators reported.

Dolutegravir-based ART appeared to be comparable to efavirenz-based therapy at viral suppression with a similar safety profile, although the trial was not powered for head-to-head comparison, said Kelly Dooley, MD, of Johns Hopkins University, Baltimore.

“We know that rifampin reduces concentrations of dolutegravir substantially, but that drug interaction can be mitigated by increasing the dose of dolutegravir to twice daily. That information was from a healthy volunteer trial, so we thought it would be important to test HIV/TB cotreatment among patients who have both infections,” she said at the Conference on Retroviruses and Opportunistic Infections.

Dr. Dooley and her colleagues looked at dolutegravir or efavirenz plus rifampin-based TB therapy in the INSPIRING trial.

 

The ongoing study is a phase 3b, noncomparative, randomized, open-label trial in ART-naive adults with HIV-1 and drug-sensitive TB infections.

In a briefing following her presentation of the data in an oral session, Dr. Dooley explained that the reason for the parallel but noncomparative arms in the trial was that it was primarily designed to see how dolutegravir works in HIV/TB coinfected patients. Enrollment of 113 patients from 37 sites in seven countries took about 2 years, and it would have required significantly more time to enroll the more than 500 patients necessary for an adequately powered comparison trial.

The trial was conducted in Argentina, Brazil, Mexico, Peru, Russia, South Africa, and Thailand. Dr. Dooley presented results from a 24-week interim analysis.

Participants who were on rifampin-based TB therapy for up to 8 weeks were randomized on a 3:2 basis to receive either dolutegravir 50 mg twice daily during and for 2 weeks post-TB therapy, followed by 50 mg once daily (69 patients), or efavirenz 600 mg daily plus two nucleoside reverse transcriptase inhibitors of the investigator’s choice for 52 weeks.

 

At 24 weeks, the percentage of patients deemed to have virologic success, defined as HIV-1 RNA less than 50 copies/mL, was 81% in the dolutegravir arm and 89% in the efavirenz arm. The respective rates of virologic nonresponse were 10% and 7%. No virologic data were available because of treatment discontinuations or missing information for 9% and 5% of patients, respectively.

The difference in response rates between the arms was due to non–treatment associated withdrawals among patients on dolutegravir, Dr. Dooley said.

Virologic withdrawals for confirmed plasma HIV-1 RNA of 400 copies/mL or more at or after week 24 for two consecutive tests occurred in one patient on dolutegravir and in none on efavirenz. There were no treatment-emergent resistance-associated mutations to any anti-HIV drugs in the dolutegravir group (data not available for the efavirenz group).

Two patients, both in the efavirenz arm, discontinued therapy because of adverse events. TB-associated rates of the immune reconstitution inflammatory syndrome (IRIS) occurred in 4% of patients in each treatment arm. No patients discontinued therapy because of IRIS or liver-related adverse events.

“We think that this study provides evidence that dolutegravir is effective and well tolerated in adults with HIV/TB coinfection who are receiving rifampin-based tuberculosis therapy, and we hope that this will increase the number of options for TB/HIV coinfected patients for whom there are relatively few treatment possibilities,” she concluded.

Dr. Dooley reported research support via her university from ViiV Healthcare, which funded the study.

[email protected]

SOURCE: Dooley K et al. Abstract 33.