CROI: Conference on Retroviruses and Opportunistic Infections

BOSTON – A combination regimen of rifapentine­ plus isoniazid (1HP) can do in 1 month what it takes isoniazid monotherapy 9 months to accomplish: effectively prevent tuberculosis in persons with HIV infection, investigators in the randomized phase 3 BRIEF TB trial reported.

“Rates of tuberculosis or death in individuals on 1HP were essentially identical to the rates of tuberculosis or death in people who got the 9-months regimen,” said Richard Chaisson, MD, of Johns Hopkins University, Baltimore.

“People who got the 1-month regimen were more likely to complete it, had slightly less toxicity, and overall had very similar clinical outcomes,” he said at the annual Conference on Retroviruses & Opportunistic Infections.

Worldwide, more than 1,000 persons with HIV infection die from tuberculosis every day, he noted.

Although isoniazid preventive therapy (IPT) is highly effective, the rate of its use has been “appallingly poor,” Dr. Chaisson said.

“There’s a sense of futility amongst clinicians around the world, that they’re not going to even bother with giving TB-preventive therapy,” he commented.

Neil Osterweil/Frontline Medical News

Dr. Chaisson and coinvestigators conducted a randomized trial to test the hypothesis that 4 weeks of daily rifapentine and isoniazid would be noninferior to 9 months of isoniazid for TB prevention in person with HIV infection.

In a multicenter open-label trial, they enrolled 3,000 HIV-infected people aged 13 years and older from 45 sites in 10 countries. The patients had no evidence of active TB, but had either tuberculin skin test (TST) reactivity of 5 mm or greater and/or a positive interferon gamma release assay (IGRA), or lived in a high–TB burden area (prevalence of 60 or more cases per 100,000 population).

Patients were stratified by CD4+ cell count and antiretroviral therapy use at base line (yes or no). The median CD4 count was 470 cells/mm³, and 50% of patients were on ART. Only efavirenz-based or nevirapine-based ART was allowed during IPT therapy.

In the experimental arm, patients were randomized to 4 weeks of rifapentine 450 mg for those less than 45 kg, or 600 mg for those 45 kg or higher, plus 300 mg isoniazid daily, plus 25 mg vitamin B6, followed by 32 weeks of observation.

Patients in the control arm received isoniazid and vitamin B₆ daily for 36 weeks.

 A total of 1,498 patients assigned to standard-of-care isoniazid and 1,488 assigned to 1HP were available for the efficacy analysis.

Three years after the last patient had been enrolled, the primary endpoint – the incidence rate of first diagnosis of active TB, TB death, or death from an unknown cause – had occurred in 32 patients on the 1HP regimen, and 33 on 9-month isoniazid.

Events included confirmed active TB in 18 patients on 1HP and 14 on isoniazid, probable active TB in 11 and 10 patients, respectively, death related to TB in 2 patients on 9-month isoniazid (none in the 1HP group) and death from unknown causes in 3 and 7 patients, respectively.

The incidence of events per 100 person-years of follow-up was 0.65 for the 1HP regimen and 0.67 for 9 months of isoniazid, a difference that was not statistically significant.

There were two cases of isoniazid resistance and one of rifampin resistance in the 1HP arm vs. one each in the 9-month isoniazid arm. There were no cases of multidrug resistance in either arm.

The safety analysis showed that 83 patients on 1HP had at least one serious adverse event, compared with 108 patients on the 9-month regimen.

“This 1 HP regimen really could dramatically alter the landscape for preventing TB in people with HIV. It’s a simple regimen; it can be given to people with HIV, and the likelihood of them completing it is extremely high; and the likelihood of it working is extremely good,” Dr. Chaisson said at media briefing following his presentation of the data in session.

The study was funded by National Institute of Health grants. Sanofi supplied study medications. Dr. Chaisson disclosed serving as a consultant to Otsuka, and that his spouse is a Merck shareholder.

BOSTON – A combination regimen of rifapentine­ plus isoniazid (1HP) can do in 1 month what it takes isoniazid monotherapy 9 months to accomplish: effectively prevent tuberculosis in persons with HIV infection, investigators in the randomized phase 3 BRIEF TB trial reported.

“Rates of tuberculosis or death in individuals on 1HP were essentially identical to the rates of tuberculosis or death in people who got the 9-months regimen,” said Richard Chaisson, MD, of Johns Hopkins University, Baltimore.

“People who got the 1-month regimen were more likely to complete it, had slightly less toxicity, and overall had very similar clinical outcomes,” he said at the annual Conference on Retroviruses & Opportunistic Infections.

Worldwide, more than 1,000 persons with HIV infection die from tuberculosis every day, he noted.

Although isoniazid preventive therapy (IPT) is highly effective, the rate of its use has been “appallingly poor,” Dr. Chaisson said.

“There’s a sense of futility amongst clinicians around the world, that they’re not going to even bother with giving TB-preventive therapy,” he commented.

Neil Osterweil/Frontline Medical News

Dr. Chaisson and coinvestigators conducted a randomized trial to test the hypothesis that 4 weeks of daily rifapentine and isoniazid would be noninferior to 9 months of isoniazid for TB prevention in person with HIV infection.

In a multicenter open-label trial, they enrolled 3,000 HIV-infected people aged 13 years and older from 45 sites in 10 countries. The patients had no evidence of active TB, but had either tuberculin skin test (TST) reactivity of 5 mm or greater and/or a positive interferon gamma release assay (IGRA), or lived in a high–TB burden area (prevalence of 60 or more cases per 100,000 population).

Patients were stratified by CD4+ cell count and antiretroviral therapy use at base line (yes or no). The median CD4 count was 470 cells/mm³, and 50% of patients were on ART. Only efavirenz-based or nevirapine-based ART was allowed during IPT therapy.

In the experimental arm, patients were randomized to 4 weeks of rifapentine 450 mg for those less than 45 kg, or 600 mg for those 45 kg or higher, plus 300 mg isoniazid daily, plus 25 mg vitamin B6, followed by 32 weeks of observation.

Patients in the control arm received isoniazid and vitamin B₆ daily for 36 weeks.

 A total of 1,498 patients assigned to standard-of-care isoniazid and 1,488 assigned to 1HP were available for the efficacy analysis.

Three years after the last patient had been enrolled, the primary endpoint – the incidence rate of first diagnosis of active TB, TB death, or death from an unknown cause – had occurred in 32 patients on the 1HP regimen, and 33 on 9-month isoniazid.

Events included confirmed active TB in 18 patients on 1HP and 14 on isoniazid, probable active TB in 11 and 10 patients, respectively, death related to TB in 2 patients on 9-month isoniazid (none in the 1HP group) and death from unknown causes in 3 and 7 patients, respectively.

The incidence of events per 100 person-years of follow-up was 0.65 for the 1HP regimen and 0.67 for 9 months of isoniazid, a difference that was not statistically significant.

There were two cases of isoniazid resistance and one of rifampin resistance in the 1HP arm vs. one each in the 9-month isoniazid arm. There were no cases of multidrug resistance in either arm.

The safety analysis showed that 83 patients on 1HP had at least one serious adverse event, compared with 108 patients on the 9-month regimen.

“This 1 HP regimen really could dramatically alter the landscape for preventing TB in people with HIV. It’s a simple regimen; it can be given to people with HIV, and the likelihood of them completing it is extremely high; and the likelihood of it working is extremely good,” Dr. Chaisson said at media briefing following his presentation of the data in session.

The study was funded by National Institute of Health grants. Sanofi supplied study medications. Dr. Chaisson disclosed serving as a consultant to Otsuka, and that his spouse is a Merck shareholder.

BOSTON – A combination regimen of rifapentine­ plus isoniazid (1HP) can do in 1 month what it takes isoniazid monotherapy 9 months to accomplish: effectively prevent tuberculosis in persons with HIV infection, investigators in the randomized phase 3 BRIEF TB trial reported.

“Rates of tuberculosis or death in individuals on 1HP were essentially identical to the rates of tuberculosis or death in people who got the 9-months regimen,” said Richard Chaisson, MD, of Johns Hopkins University, Baltimore.

“People who got the 1-month regimen were more likely to complete it, had slightly less toxicity, and overall had very similar clinical outcomes,” he said at the annual Conference on Retroviruses & Opportunistic Infections.

Worldwide, more than 1,000 persons with HIV infection die from tuberculosis every day, he noted.

Although isoniazid preventive therapy (IPT) is highly effective, the rate of its use has been “appallingly poor,” Dr. Chaisson said.

“There’s a sense of futility amongst clinicians around the world, that they’re not going to even bother with giving TB-preventive therapy,” he commented.

Neil Osterweil/Frontline Medical News

Dr. Chaisson and coinvestigators conducted a randomized trial to test the hypothesis that 4 weeks of daily rifapentine and isoniazid would be noninferior to 9 months of isoniazid for TB prevention in person with HIV infection.

In a multicenter open-label trial, they enrolled 3,000 HIV-infected people aged 13 years and older from 45 sites in 10 countries. The patients had no evidence of active TB, but had either tuberculin skin test (TST) reactivity of 5 mm or greater and/or a positive interferon gamma release assay (IGRA), or lived in a high–TB burden area (prevalence of 60 or more cases per 100,000 population).

Patients were stratified by CD4+ cell count and antiretroviral therapy use at base line (yes or no). The median CD4 count was 470 cells/mm³, and 50% of patients were on ART. Only efavirenz-based or nevirapine-based ART was allowed during IPT therapy.

In the experimental arm, patients were randomized to 4 weeks of rifapentine 450 mg for those less than 45 kg, or 600 mg for those 45 kg or higher, plus 300 mg isoniazid daily, plus 25 mg vitamin B6, followed by 32 weeks of observation.

Patients in the control arm received isoniazid and vitamin B₆ daily for 36 weeks.

 A total of 1,498 patients assigned to standard-of-care isoniazid and 1,488 assigned to 1HP were available for the efficacy analysis.

Three years after the last patient had been enrolled, the primary endpoint – the incidence rate of first diagnosis of active TB, TB death, or death from an unknown cause – had occurred in 32 patients on the 1HP regimen, and 33 on 9-month isoniazid.

Events included confirmed active TB in 18 patients on 1HP and 14 on isoniazid, probable active TB in 11 and 10 patients, respectively, death related to TB in 2 patients on 9-month isoniazid (none in the 1HP group) and death from unknown causes in 3 and 7 patients, respectively.

The incidence of events per 100 person-years of follow-up was 0.65 for the 1HP regimen and 0.67 for 9 months of isoniazid, a difference that was not statistically significant.

There were two cases of isoniazid resistance and one of rifampin resistance in the 1HP arm vs. one each in the 9-month isoniazid arm. There were no cases of multidrug resistance in either arm.

The safety analysis showed that 83 patients on 1HP had at least one serious adverse event, compared with 108 patients on the 9-month regimen.

“This 1 HP regimen really could dramatically alter the landscape for preventing TB in people with HIV. It’s a simple regimen; it can be given to people with HIV, and the likelihood of them completing it is extremely high; and the likelihood of it working is extremely good,” Dr. Chaisson said at media briefing following his presentation of the data in session.

The study was funded by National Institute of Health grants. Sanofi supplied study medications. Dr. Chaisson disclosed serving as a consultant to Otsuka, and that his spouse is a Merck shareholder.