Conference Coverage

Intensified rifampicin boosts outcomes in TB/HIV coinfection


AT AIDS 2016


DURBAN, SOUTH AFRICA – Prescribing high-dose rifampicin in addition to antiretroviral therapy reduces 12-month all-cause mortality in patients who are coinfected with tuberculosis and HIV and who have a low CD4 cell count, Corinne S. Merle, MD, reported at the 21st International AIDS Conference.

“Current strategies to reduce TB/HIV mortality rely largely on optimal management of HIV disease with early ART [antiretroviral therapy]. We wanted to look at whether there is value in focusing on the TB side of the problem. This is the first study to look at more intensive TB therapy for reducing mortality; and we think that, at least in patients who are immunosuppressed, there might be some benefit in a more aggressive TB treatment from the start,” said Dr. Merle of the London School of Hygiene and Tropical Medicine.

Dr. Anton Pozniak

Dr. Anton Pozniak

She presented the results of the open-label, multicenter trial of 747 ART-naive adults from West Africa. All were coinfected with TB/HIV and had a CD4 count of at least 50 cells/mm3 at enrollment. They were randomized to one of three treatment arms: ART starting at 2 weeks combined with standard TB treatment; ART starting at 8 weeks plus standard TB therapy; or ART initiation at 8 weeks coupled with 2 months of high-dose rifampicin (Rifadin) at 15 mg/kg daily, followed by standard TB therapy. None of the participants had multidrug-resistant TB. More than one-quarter of them were undernourished as evidenced by a baseline body mass index below 16 kg/m2.

The primary outcome was all-cause mortality at 12 months. There was no significant difference between the study arms, with a 10% rate in the intensified TB treatment arm and mortality rates of 11% and 14% with standard TB therapy and ART starting after 2 and 8 weeks, respectively.

However, a prespecified secondary analysis restricted to the 159 subjects with a baseline CD4 count below 100 cells/mm3 struck gold. Overall 12-month mortality was 4% in the intensified TB treatment subgroup, compared with 19% in patients on standard TB therapy with ART starting at 2 weeks and 28% with ART starting at 8 weeks. In a Cox regression analysis, severely immunosuppressed patients in the high-dose rifampicin group were an adjusted 88% less likely to die within 12 months than those on standard TB treatment with ART starting at 8 weeks and 80% less likely to die than those starting ART at 2 weeks.

At 18 months after randomization, roughly three-quarters of patients in each study arm had undetectable HIV viral loads.

There was no evidence of an increased risk of hepatotoxicity with 2 months of high-dose rifampicin. Only 4 of nearly 3,800 aspartate aminotransferase measurements obtained during the trial showed grade 3 or 4 hepatotoxicity, Dr. Merle noted.

In a plenary lecture on TB/HIV coinfection at the AIDS 2016 conference, Anton Pozniak, MD, singled out the trial as a sterling example of how to optimize available clinical management tools while awaiting a desperately needed new TB vaccine and better drugs.

More than 1 million new TB cases occur annually in HIV-infected persons, roughly 80% of them in sub-Saharan Africa. There are now 400,000 deaths per year worldwide in coinfected TB/HIV patients. Indeed, TB has become the No. 1 cause of death among people living with HIV infection, said Dr. Pozniak, director of HIV services at Chelsea and Westminster Hospital in London.

He offered a road map to eliminating TB by the year 2035. At present, the global trend is a 2% per year decline in new cases. Optimizing TB case finding, treatment, and preventive therapy could achieve a 10% per year decrease in new cases. That rate still wouldn’t reach the goal by 2035. But more than a dozen candidate TB vaccines are in the developmental pipeline, including a mycobacterial whole cell extract in phase III testing in China. If a new vaccine can be introduced by 2025, that would be a game changer.

“A new vaccine that could prevent adolescents and adults from developing and transmitting TB would be the single most cost-effective tool in mitigating the epidemic,” he said. “Even if we had only a 60% efficacious vaccine and delivered it to 20% of the target population, it could potentially avert 30-50 million incident cases of TB by 2050.”

A new vaccine plus effective alternatives to the standard 6 months of isoniazid for latency prophylaxis by 2025 are estimated to reduce new cases of TB by an average of 17% per year. That circumstance would mean the end of TB by 2035, Dr. Pozniak declared.


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