TB-HIV trials triumph

by VIVIAN ATTWOOD

A Durban-based treatment study at the Centre for the Aids Programme of Research in South Africa (Caprisa) has proved convincingly that mortality among co-infected TB-HIV patients can be reduced by at least 55% if antiretroviral therapy (ART) is provided in conjunction with TB treatment.

The breakthrough, which could significantly prolong the lives of an incalculable number of co-infected patients in future, was announced by Prof Salim Abdool Karim, director of Caprisa, at a media symposium yesterday.

Stressing that "the real heroes are not the researchers, but those who volunteered for the study, and adhered to its requirements", Karim said that while it was standard policy not to unveil medical discoveries until research had been published in reputable journals, the significance of the breakthrough merited an immediate announcement of the study's findings.

"We are in the unique situation of having a very large number of people infected with both HIV and TB," Karim said.

"One of the studies we were conducting, called START, was forced to stop, rather prematurely. It proved an unfortunate choice of name, but it did pose a key question, namely: what is the relationship between TB drugs and antiretrovirals?

Randomly

"This launched an open-ended, randomised trial known as the Sapit (Starting Antiretrovirals at Three Points in Tuberculosis) trial.
"TB-HIV co-infected patients assigned randomly to receive ART together with their TB treatment (integrated treatment arm) were compared with patients assigned to receive ART once they completed TB treatment (sequential treatment arm)."

The trial was conducted at the Caprisa eThekwini TB-HIV Clinic attached to the Prince Cyril Zulu TB Clinic.

Headed by Karim, the study commenced in June 2005 and enrolment was completed in July this year.

"Until this point, doctors have tended to tailor the onset of ART and TB treatment to suit individual patients," Karim explained. "We needed solid evidence to justify the way in which co-infected HIV-TB patients were medicated."

The trial involved 645 co-infected patients. Of these, 431 were enrolled in the integrated treatment arm and 214 in the sequential treatment arm.

Twenty-six patients in the sequential treatment arm died (a mortality rate of 11.6 per 100 person years), as opposed to 24 patients who died in the integrated treatment arm (a mortality rate of 5.1 per 100 person years).

As a result, an independent Safety Monitoring Committee affiliated to the study recommended this month that the sequential arm of the trial be stopped and ART be started in that group at once.

It further recommended that the two sub-groups in the integrated treatment arm (early TB-HIV treatment, and post-intensive phase TB-HIV treatment) continue.

Reasons

Karim said the team had initially been posed with some convincing reasons not to initiate ART during TB treatment.

Chief among these were:

* Drug interactions between the chief TB drug, Rifampicin, and many ARVs.

In conjunction, it was found, Rifampicin produces enzymes which metabolise ARVs, meaning that optimum levels of the TB drug are not achieved.

* Some patients found the burden of taking 4 TB drugs a day, in conjunction with 3 ARVs, intolerable, with symptoms of severe nausea and vomiting as the drugs were metabolised in the liver.

* There was an increased likelihood of immune reconstruction syndrome, or IROS, whereby TB medication, or ART, produced an improvement in the immune system, followed by a paradoxical worsening in the patient's condition.

Criteria for including patients in the study were: they had to be sputum positive for TB and on a standard anti-TB therapy programme; they had to be HIV-positive; they had to have a CD4 count lower than 500; and women had to agree to use contraception during the trial.

Summarising the Sapit trial findings, Karim said: "There is compelling evidence for changing clinical practice countrywide, and integrating TB and HIV care."

Karim said of the programme that if 150 000 more TB patients were given ART each year, 10 000 deaths could be averted annually.

It is estimated that 70% of all South Africans with TB are infected with HIV.