Greater Cancer Risk for Persons With HIV/AIDS, FDA to Review Merck’s Isentress, VivaGel Trial for Sexually Active Women

August 2, 2007

A new report shows that persons with HIV/AIDS and transplant patients are much more likely to contract about 20 different cancers than those in the general population (McLean T. Australian Associated Press. June 6, 2007). Conducted by the University of New South Wales, the study found that immune deficiency-a problem common to the 2 groups-makes them more vulnerable to infections and cancers, including those in the liver, stomach, skin, lung, cervix, eye, lip, mouth, and penis.

HIV/AIDS and Transplant Patients More Likely to Get Cancer
A new report shows that persons with HIV/AIDS and transplant patients are much more likely to contract about 20 different cancers than those in the general population (McLean T. Australian Associated Press. June 6, 2007). Conducted by the University of New South Wales, the study found that immune deficiency-a problem common to the 2 groups-makes them more vulnerable to infections and cancers, including those in the liver, stomach, skin, lung, cervix, eye, lip, mouth, and penis.

Lead author Andrew Grulich and colleagues analyzed cancer rates among persons with HIV/AIDS and those who had a kidney transplant and found a “marked increased risk.” Both groups’ impaired immunity increased their chances of contracting viruses and developing cancers linked to them.

Hodgkin lymphoma, a cancer associated with Epstein-Barr virus, was 11 times more likely to develop in persons with HIV/AIDS. Transplant patients had a 4-fold risk, as well as a greater chance of contracting cancers related to human papillomavirus, such as cervical, penile, and anal cancers.

Liver cancer rates were 5 times higher in HIV-infected patients and double in transplant patients. Similar dangers were found for cancer of the lung, stomach, eye, larynx, lip, and esophagus. The investigators found no increased risk for more common, non–infection-related cancers, such as breast and prostate cancers.

Previous research had linked 3 cancers to HIV infection, but scientists had thought the risk was fueled by lifestyle. This is the first study to compare the rates in 2 different groups with 1 shared problem.

“The only thing that people with AIDS and transplant recipients share is immune deficiency; otherwise their risk factors for cancer differ markedly” said Grulich. “This strongly suggests to us that it’s the immune situation rather than [any] lifestyle issues that are behind this.”

Grulich said that those with HIV infection may need to start antiretroviral therapy earlier to maintain their immune systems, and that new drugs need to be developed for transplant patients. Such drugs would stop organ rejection without so heavily suppressing the immune system.

The researchers will next study people with congenital immune deficiency and those who have received other transplants, such as a heart or liver. Results of the study appeared in The Lancet (Grulich AE, van Leeuwen MT, Falster MO, Vadjic CM. Lancet. 2007;370:59-67). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Thursday, July 12, 2007]

FDA Expert Panel to Review Merck’s New HIV Treatment Isentress in September
On September 5, the FDA’s antiviral panel will meet to assess the safety and efficacy of Isentress (raltegravir), the first HIV integrase inhibitor to reach this stage of FDA review, from Merck & Co (Associated Press. July 11, 2007). The drug’s target market is the patient who no longer responds to at least 1 drug in any of the 3 traditional antiretroviral classes. Last month, the FDA granted priority review status to Isentress, a designation that acknowledges the candidate drug fills an urgent medical need and also reduces the length of the review period from 10 months to 6.

Merck said its trials show Isentress effectively reduced HIV viral load in more than 75% of study patients. The FDA typically follows the advice of its expert panels; a final decision is anticipated by mid-October. [CDC HIV/Hepatitis/STD/TB Prevention News Update, Thursday, July 12, 2007]

Trials Begin on HIV Gel for Women
Forty women in the United States are taking part in a 2-week trial of a vaginal microbicide designed to block HIV and other pathogenic causes of sexually transmitted disease (STDs), Australia-based Starpharma Holdings Ltd, the drug’s maker, said today (Australian Associated Press. July 10, 2007).

VivaGel is currently being tested at the University of South Florida and at the University of Puerto Rico in sexually active, HIV-negative women who are between 18 and 24 years old.

The goal of the NIH-funded trial is to determine the safety and ease of use of VivaGel, said Dr Jackie Fairley, StarPharma’s chief. “We have already conducted clinical trials on the safety of VivaGel in sexually inactive women and men, but this is the first time the product will be used in sexually active young women, one of our target populations,” said Fairley.

The drug maker cited statistics that show 60% of US women with HIV are in the 15 to 24 age group, highlighting how critical such a product could become to young women. “This study, in addition to the usual safety data, will collect valuable information regarding the product’s use and acceptability in the consumer setting,” said Fairley. “The data from this trial will provide information of value to the development of VivaGel for all indications, including preventing the spread of genital herpes.” [CDC HIV/Hepatitis/STD/TB Prevention News Update, Tuesday, July 10, 2007]

German Scientists Snip AIDS Virus Out of Human Cells

In a recent test tube experiment, scientists engineered an enzyme that cut the DNA for producing HIV from human cells, leaving the rest of the DNA intact and HIV-free (Deutsche Presse-Agentur. June 28, 2007). Three years of experiments on mice are planned; if they are successful, human trials could follow.

The laboratory research used a new recombinase enzyme, Tre, which removed DNA at certain segments and then recombined the remaining strands. Tre was engineered through more than 120 generations from a naturally occurring enzyme, Cre, which recognizes similar genetic sequences, scientists said. After Tre cut HIV-specific genes out of the host’s DNA, the cell flushed out the targeted DNA fragment as waste. “After that it is healthy,” said Joachim Hauber of Hamburg’s Heinrich Pette Institute for Experimental Virology.

“We have rid the cells of the virus. No one else has done this before. It’s a breakthrough in biotechnology,” added Hauber. The Max Planck Institute for Molecular Cell Biology and Genetics was an equal partner with the Pette Institute in the research.

The procedure offers hope for some day curing AIDS, Hauber said. But any therapy would require stem cells from the patient’s blood, treated in the laboratory and re-injected for the immunotherapy, he said. “It’s high-tech medicine. You couldn’t just take a pill.”

The complete report, “HIV-1 Proviral DNA Excision Using an Evolved Recombinase,” was published in Science (Sarkar I, Hauber I, Hauber J, Buchholz F. Science. 2007;316:1912-1915). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Tuesday, July 10, 2007]

New Medication May Benefit Drug-Resistant AIDS Patients
In 2 new international studies, an experimental NNRTI significantly lowered blood viral levels in patients failing standard treatments (Chong J-R. Los Angeles Times. July 6, 2007). The new drug, etravirine, blocks an enzyme HIV needs to replicate. The drug is produced by Tibotec Pharmaceuticals, which funded the studies. The effects were observed in a treatment combining etravirine, previously known as TMC125, and Tibotec’s new protease inhibitor Prezista (darunavir).

The studies enrolled 1203 HIV-infected patients in 19 countries who were resistant to NNRTIs and protease inhibitors. At 24 weeks, the number of HIV RNA copies dropped to undetectable levels in 18% more patients in the study group treated with the etravirine-darunavir combination than in those receiving a standard drug regimen.

The first study found 56% of etravirine-treated patients had undetectable viral loads, compared with 39% in the placebo–standard regimen group. In the second study, 62% of patients receiving etravirine achieved undetectable HIV RNA levels compared with 44% in the placebo–standard regimen group. Side effects were mild or moderate and occurred at about the same rate in both treatment groups. Etravirine did not help a subset of patients taking the entry inhibitor Fuzeon (enfuvirtide) for the first time.

“There are a lot of patients out there who need salvage therapy with a new NNRTI, and it looks like we’ll have one,” said Dr Mark Wainberg, director of Montreal’s McGill University AIDS Center. He was not involved in the study but has consulted for Tibotec.

Tibotec will seek FDA approval for etravirine in the next few months.

Results of the 2 studies, DUET-1 and DUET-2, were published in The Lancet (Madruga JV, Cahn P, Grinsztejn B, et al; DUET-1 Study Group. Lancet. 2007;370:39-48 and 370:39-48, respectively). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Thursday, July 5, 2007]