/ 19 January 2006

‘Important’ advance in Aids research

It is better to take anti-retrovirals continually as regular breaks can cause further health problems, a United States study which included South Africans said this week.

Announcing that enrolment into the international study would be halted, the US’s National Institute for Allergy and Infectious Diseases (NIAID) said findings showed continuous anti-retroviral therapy (ART) was better.

Taking regular breaks to avoid side effects and to save money, was more than twice as likely to make people ill.

The study, conducted by the research arm of the US government’s Department of Health, compared levels of continuous ART with episodic drug treatment guided by levels of CD4+ cells — an indicator of the progression of the disease.

”Enrolment was stopped because those patients receiving episodic therapy had twice the risk of disease progression [the development of clinical Aids or death], the major outcome of the study.”

The enrolment halt was made in collaboration with the study’s executive committee and following a recommendation received from an independent Data and Safety Monitoring Board (DSMB), which had reviewed interim study data in early January said NIAID.

”It’s an important finding and important scientific advance,” said the Treatment Action Campaign’s Nathan Geffen.

”It just proves to the denialists that people who continuously take ART do much better than people who only take it occasionally,” he said, referring to the controversy over which treatment is preferable for the disease which does not yet have a scientifically acknowledged cure.

The trial, known as Strategies for Management of Anti-Retroviral Therapy, or Smart, was designed to determine which of two different HIV treatment strategies was better.

Geffen said that treatment breaks could have had a number of benefits — they provided patients with a respite from the side effects of taking chronic medication, and had cost implications.

”It’s no fun taking chronic medication every day,” Geffen said.

A NIAID fact sheet said that researchers also wanted to know more about toxicity in long term ART.

HIV-positive volunteers were assigned at random to either a viral suppression strategy, in which ART was taken on an ongoing basis to suppress HIV viral load, or a drug conservation strategy, in which ART was started only when the levels of key immune cells, called CD4+ cells, dropped below 250 cells per cubic millimetre

(mm3).

Volunteers in the drug conservation group were taken off ART with the aims of reducing drug side effects and preserving treatment options whenever their CD4+ cells were above 350 cells/mm3.

At the time of the DSMB review, the average follow-up was approximately 15 months.

The analysis revealed that participants taking the breaks (guided by their higher CD4 levels) faced more than twice the risk of disease progression than the participants on continuous ART.

”Furthermore, there was an increase in major complications such as cardiovascular, kidney and liver diseases in the participants on the drug conservation arm. These complications have been associated with ART, and it was hoped that they would be seen less frequently in those patients receiving less drugs,” said NIAID.

Although the risk-to-benefit ratio over the longer term remained uncertain, the DSMB recommended that enrolment into the trial be halted in light of the findings.

It was decided to re-initiate therapy in patients who in the drug-break part of the study and the study physicians and participants were being notified of the findings and recommendations.

Follow up visits would continue for all participants in the trial while the study team considered plans for a longer follow-up.

NIAID said that the clinicians and participants should be commended for their contribution to the study, which came to a conclusion faster than expected after it began in 2002. – Sapa