Combining HIV and TB Therapy Saves Lives

By Michael Smith
CAPETOWN, South Africa, 20 oct 2008-- Treating HIV and tuberculosis at the same time reduces mortality by 55% compared with delaying HIV treatment until TB therapy is complete, researchers here said.
The finding should change clinical practice, according to Salim Abdool Karim, M.D., Ph.D., of the Centre for the AIDS Program of Research in South Africa (CAPRISA) and the Mailman School of Public Health at Columbia in New York.
Dr. Karim is principal investigator of the so-called SAPIT trial (for Starting Anti-retroviral therapy (ART) in three Points In Tuberculosis therapy), which is exploring treatment options for people with both infections.
But the sequential treatment arm of the randomized open-label study was halted early, when a planned data review in September showed it had an excess mortality rate, compared with integrated HIV and TB treatment, Dr. Karin said.
The mortality rate among patients treated sequentially was more than double that among patients treated for both diseases at the same time -- 11.6 deaths per 100 person-years, versus 5.1.
The difference was statistically significant at P=0.0049, the study's data monitoring committee found.
The committee recommended that the sequential treatment arm be halted and that patients be offered the opportunity to begin anti-retroviral therapy during their TB treatment, Dr. Karim and colleagues said.
"The study shows that integrating TB and HIV treatment and care saves lives," Dr. Karim said. He added the study offers "compelling evidence" for changing clinical practice.
The study enrolled 645 patients and randomized them to three treatment arms:
214 patients were treated sequentially, with HIV drugs delayed until after the completion of standard TB therapy.
Half of the remaining 431 patients were treated with HIV drugs during the first two months of TB therapy -- the early integrated treatment arm.
The other patients were treated after the first phase of TB therapy, but before it was complete -- the late integrated therapy arm.
For the September data review, the committee considered the integrated arms together, finding that 24 patients on integrated therapy had died since the start of the trial. In the smaller sequential arm, 26 patients had died.
The reduction in mortality was statistically significant regardless of the patient's CD4 cell count, the committee said.
The two integrated treatment arms of the study will continue, the researchers said.
Clinicians have been reluctant to combine HIV and TB treatment for co-infected patients, fearing drug interactions, increased pill burden and decreased tolerability, and a greater likelihood of immune reconstitution syndrome.
On the other hand, co-infection speeds the progression of HIV and increases mortality. An estimated 70% of all TB patients in South Africa are infected with HIV.
"The results to date clearly show the urgent necessity to make ART available to HIV-infected patients with TB worldwide," said Paul Nunn, M.D., of the Stop TB Department of the World Health Organization.
In South Africa alone, he said, such a policy would mean an additional 100,000 to 150,000 TB patients would start HIV therapy, resulting in about 10,000 deaths averted yearly.
A spokesperson for Dr. Karim said a manuscript detailing the results is being prepared for publication.
The study was supported by CAPRISA, the NIH, the President's Emergency Plan for AIDS Relief, and the Global Fund to fight AIDS, Tuberculosis, and Malaria.