Washington, Genetic variations and not complying with treatment regimens may account for some failures of an anti-HIV drug to treat and prevent the infection.
The drug Tenofovir, marketed as Viread, is processed differently according to cell locations, the study said.
This is to see if the drug is eventually marketed as a topical gel, it can work differently depending on whether it is applied to the vagina or the rectum.
“Our results suggest that in future, before prescribing tenofovir to a patient, a doctor could order genetic testing and know in advance if it works, and prescribe a different drug if it won’t,” said Namandje Bumpus, associate professor of medicine at the Johns Hopkins University School of Medicine.
In the study described in the journal EBio-Medicine, the team focused on a search for the human enzymes that convert tenofovir from its original form to an activated one that combats HIV.
The team “knocked out” genes for phosphate-adding enzymes one by one, then exposed the tissues’ cells to tenofovir.
They found that the enzyme called pyruvate kinase was different from that which performed the second activation step in the colorectal tissues.
The team sequenced the genes of 142 women who had participated in a clinical trial of tenofovir to look for genetic variations that might have affected the function of the enzyme.
They found 71 such variants, several of which a computer model predicted would make the enzyme ineffective.
Altogether, eight percent of the women had genetic variants that were likely to make them unable to convert tenofovir to its activated form.
“Tenofovir has been shown in trials to be very effective, so when it does not work, researchers and clinicians tend to assume the individual just was not taking the drug as directed,” Bumpus said.
A London man appears to be free of the AIDS virus after a stem cell transplant, the second success including the “Berlin patient,” doctors reported.
The therapy had an early success with Timothy Ray Brown, a U.S. man treated in Germany who is 12 years post-transplant and still free of HIV. Until now, Brown is the only person thought to have been cured of infection with HIV, the virus that causes AIDS.
The latest case “shows the cure of Timothy Brown was not a fluke and can be recreated,” said Dr. Keith Jerome of Fred Hutchinson Cancer Research Center in Seattle who had no role. He added that it could lead to a simpler approach that could be used more widely.
The case was published online Monday by the journal Nature and will be presented at an HIV conference in Seattle.
The patient has not been identified. He was diagnosed with HIV in 2003 and started taking drugs to control the infection in 2012. It’s unclear why he waited that long. He developed Hodgkin lymphoma that year and agreed to a stem cell transplant to treat the cancer in 2016.
With the right kind of donor, his doctors figured, the London patient might get a bonus beyond treating his cancer: a possible HIV cure.
Doctors found a donor with a gene mutation that confers natural resistance to HIV. About 1 percent of people descended from northern Europeans have inherited the mutation from both parents and are immune to most HIV. The donor had this double copy of the mutation.
That was “an improbable event,” said lead researcher Ravindra Gupta of University College London. “That’s why this has not been observed more frequently.”
The transplant changed the London patient’s immune system, giving him the donor’s mutation and HIV resistance.
The patient voluntarily stopped taking HIV drugs to see if the virus would come back.
Usually, HIV patients expect to stay on daily pills for life to suppress the virus. When drugs are stopped, the virus roars back, usually in two to three weeks.
That didn’t happen with the London patient. There is still no trace of the virus after 18 months off the drugs.
Brown said he would like to meet the London patient and would encourage him to go public because “it’s been very useful for science and for giving hope to HIV-positive people, to people living with HIV,” he told The Associated Press Monday.
Stem cell transplants typically are harsh procedures which start with radiation or chemotherapy to damage the body’s existing immune system and make room for a new one. There are complications too. Brown had to have a second stem cell transplant when his leukemia returned.