New Delhi, July 28: Scientists involved in India’s first HIV vaccine trial today said they plan to review the findings of the US study that appears to link a virus used in the vaccine with liver tumours in mice.

As reported in The Telegraph today, safety concerns about the virus called adeno-associated virus (AAV) have emerged after two unrelated developments in the US on Thursday — the death of a patient who had received AAV in a gene therapy trial for arthritis and the publication of a new study in which mice injected with AAV developed liver tumours.

US authorities are still trying to determine the cause of death of the patient — and there is no evidence that it had anything to do with the AAV.

But the study of the tumours in mice given AAV injections is likely to be discussed by Indian experts, according to sources at the National AIDS Research Institute (Nari), Pune, where the HIV vaccine trial was conducted.

The US study by Mark Sands at Washington University, St Louis, and David Russel at the University of Washington, Seattle, showed that an unusually high proportion of mice injected with AAV developed liver tumours.

In one set of their experiments, seven out of 13 (54 per cent) of normal, healthy mice that received AAV gene therapy developed liver tumours against only four out of 52 (8 per cent) normal mice that did not receive AAV.

“Tumours in healthy mice is unusual — why should this happen? We need to understand this,” a senior scientist at Nari who requested anonymity told The Telegraph.

The institute will approach the International AIDS Vaccine Initiative (IAVI) — an organisation that had helped Nari select the candidate vaccine — to hold a meeting of toxicologists, clinicians and virologists to review the study, sources said.

The candidate HIV vaccine uses AAV to deliver HIV genes. The trial concluded earlier this year and scientists said there have been no serious side effects in any of the volunteers.

Several AAV experts point out that the use of this virus as a delivery vehicle for genes began only after extensive studies on monkeys and other animals had established its safety.

In one set of studies, dogs given AAV were followed up for up to 10 years and there were no adverse events, and no liver tumours, said Philip Johnson, a leading AAV expert at The Children’s Hospital of Philadelphia.

But Washington University’s Sands says most animal studies were short-term.

The first concerns about tumours and AAV emerged in 2001 when Sands and his colleagues found that mice that had received AAV developed liver tumours after 18 months, but the findings were “largely dismissed”, Sands said.

Following the study, the US Food and Drug Administration had convened a meeting of AAV experts. At the meeting, Sands said, it appeared to him that there were few long-term studies of the type that his team had conducted.

“I was surprised,” Sands told The Telegraph. But the findings of 2001 were largely dismissed because of the small number of mice used in that study — only five — and because of the absence of any molecular data.

The new study, published on Thursday in the journal Science, used more mice and has also shown that AAV inserts its genetic material in a region of the mouse DNA that is “virtually identical” to a corresponding region in human DNA.

But other experts are arguing that the mice that Sands used in his study appeared to be “very susceptible to liver cancer”. In his study on normal, healthy mice, 8 per cent of mice that had not received AAV developed the tumours.

“This is unusual, I believe, for mice and humans have a rate of about 1 to 4 per 100,000 for hepatocellular carcinoma (liver cancer). So it does not seem to be a very true model of the human disease,” said Patricia Fast, medical director with IAVI.