Dr. Robert Gallo, HIV discoverer, challenges Dr. David Ho’s line of inquiry
Late in the day on February 10, the press office in the city’s Department of Health and Mental Hygiene sent out a press release telling reporters that Dr. Thomas R. Frieden, the department’s commissioner, would make an announcement “regarding HIV/AIDS” the following day.
The next day, Frieden told a phalanx of reporters that his department had found a New York City man, in his 40s, who is infected with a strain of HIV, the virus that causes AIDS, that is resistant to three of the four classes of drugs used to treat the disease.
The virus the man has is capable of attacking the man’s immune system cells by attaching itself to two different receptors on those cells, a trait typically associated with advanced HIV infection. Most HIV are able to use just one receptor, limiting their virulence.
The man had tested negative for HIV in May of 2003, but in November 2004 he experienced flu-like symptoms and he tested positive for HIV on December 16 last year. By January, he received an AIDS diagnosis. It usually takes years to go from first becoming HIV-positive to having AIDS.
A rapid progressor infected with an aggressive virus was troubling enough to city health officials, but the man was also a meth user who reported “unprotected insertive and receptive anal intercourse with multiple partners,” according to a health department alert sent to city doctors on February 11.
“It’s a wake up call to men who have sex with men, particularly those who may use crystal methamphetamine,” Frieden said in a February 11 press statement. “Not only are we seeing syphilis and a rare sexually transmitted disease, lymphogranuloma venereum, among these men, now we’ve identified this strain of HIV that is difficult or impossible to treat and which appears to progress rapidly to AIDS.”
The fevered media reaction was predictable. The bug was dubbed a super-virus. Reporters went to AIDS groups, Web sites and coffee shops popular among gay men to find out what the community would do.
Now a chorus of scientists and AIDS activists are challenging the assertion that the New York City man is infected with a super-virus and that a new strain of HIV is threatening the gay community. They are generally not critical of the health department, but they are saying that the science that underlies the announcement is flawed.
The testing on the virus was done by the Aaron Diamond AIDS Research Center (ADARC) in New York City and ViroLogic, a California-based company. Dr. David D. Ho heads ADARC and he has served on the scientific advisory board at ViroLogic since 1995.
Some activists are pointing their fingers at Ho and suggesting that his penchant for publicity led to the announcement being made well before there was evidence to support it.
“The word would be greater than skepticism,” said Dr. Robert C. Gallo, director of the Institute of Human Virology and Division of Basic Science at the University of Maryland Biotechnology Institute and a co-discoverer of HIV, the virus that causes AIDS. “There is zero evidence at this time that this is super-HIV. We’ve had claims of super-HIV in the past. None have been borne out.”
Gallo’s view is shared by Dr. John P. Moore, a professor of microbiology and immunology at the Weill Medical College of Cornell University.
“Firstly, it’s not new that multi-drug-resistant viruses are around,” Moore said. “It’s also not new that rapidly progressing viruses are around. It’s also not new that you can have the two traits in one individual.”
While a concern is that this man may have passed this virus to his sex partners, Gallo and Moore said that drug-resistant HIV is often less effective at infecting others. This bug may be “a super wimpy virus from the transmission perspective,” Moore said.
“Transmission of multi-drug-resistant viruses is relatively inefficient,” Moore explained. “I would take this more seriously if there was a cluster [of infected men] because it would prove that the virus is transmissible.”
The Community HIV/AIDS Mobilization Project (CHAMP) issued a press release responding to Frieden’s announcement that pointed out that “two cases of rapidly-progressing virus resistant to three classes of HIV drugs” had been reported in Vancouver in 2001.
“What became of that was not a widespread multi-drug-resistant virus epidemic,” said Julie Davids, CHAMP’s executive director. “Unless there is something they aren’t telling us, this isn’t new. It isn’t accurate to say this hasn’t happened before, it has.”
Dr. Christos J. Petropoulos, vice president of research and development at ViroLogic, said this virus, even with its drug-resistant features, was healthy. “Even with these mutations it is doing as well as many or even the majority of wild-type viruses,” he said, making the point that this virus can be transmitted efficiently.
At a February 15 meeting of the Physicians’ Research Network, Dr. Martin Markowitz, the ADARC researcher who did most of the testing on this virus, said the bug was “very fit,” according to people who attended the meeting.
Gallo also questions whether the man actually has AIDS. If he was misdiagnosed with AIDS, then he would not be a rapid progressor.
To get an AIDS diagnosis, one must be HIV-positive, with a T cell count below 200—T cells are the immune system cells that HIV attacks—or have one of 24 opportunistic infections.
An early phase of HIV infection called acute or primary infection, that comes ten to 14 days after a person is first infected, can mimic the AIDS diagnosis. The acute phase is characterized by a strong level of viral replication, a highly infectious individual and, often, a low T cell count. People typically recover from acute infection and it is often misdiagnosed as flu. Such infection is typical for newly infected people, and does not indicate the onset of AIDS.
“Do we know this guy had AIDS?” Gallo said. “There is no proof this guy had AIDS.”
The health department has said that it believes the man was infected in October of 2004. An acute infection lasts, on average, for 54 days though the phase can be longer or shorter.
“If he was infected in October… then he would still be going through acute infection or primary infection,” Moore said. “I don’t think you give a diagnosis of AIDS when somebody is in primary infection.”
The man’s progression from HIV infection to AIDS could have happened in “two to three months” or “20 months,” according to the health department. While 20 months is still fast, it is not unheard of.
The time between the man’s infection and the onset of AIDS could be longer than most of the press accounts written to date have assumed.
“No one would disagree that the date of infection occurred between May of 2003 and November of 2004,” an ADARC spokesperson told Gay City News, acknowledging uncertainty as to how recently the man was actually infected.
Rapid progression could have also resulted from the state of the man’s health or his genetic make-up and not the virus. Through a spokesperson, Ho declined to comment. At the February 15 meeting, his colleague Markowitz said it was the virus and not the man that was unusual, according to attendees.
“He was very, very adamant that this is the virus and the host has very little to do with this,” said one attendee.
ViroLogic’s Petropoulos was more careful.
“The fact that this virus has many of these features in a patient who is declining quickly is something unusual,” he said. “It begs the question—is it the virus that is driving this disease or is it something about the patient’s inability to fend off the virus?”
Petropoulos said the answer to that question will likely not be known for months.
Moore and Gallo also said that drug resistance has been an ongoing problem for treating AIDS. Drug resistance can happen in people who have been infected for many years and people can be infected with drug-resistant virus.
“Ten percent of new infections are resistant to some drugs,” Moore said.
Moore and Gallo did not criticize Ho or the city health department announcement even as they questioned its usefulness. In their view, the publicity may prove prudent if it results in identifying men who were infected with this virus. There is a downside, however.
“There could be a harm if you start believing in super-viruses,” Gallo said. “Isn’t there a story about the boy who cried wolf?”
Moore was charitable toward the health department.
“I suspect that they went with the information they had,” he said. “I question whether they got the best possible information… I think they acted in good faith. I’m not sure that applies right down the food chain.”
Richard Jefferys, basic science project director at the Treatment Action Group, an AIDS advocacy and research organization, was more critical.
“The feeling that we have is that it was almost certainly premature,” Jefferys said. “From what we understand, based on the news that has been released, to call this a new strain is just incorrect.”
Another concern was that should this man turn out to be the only person infected with this virus, gay men may no longer see the health department as credible.
“There is a concern that if you use misinformation as a prevention message as that unravels it will almost certainly backfire,” Jefferys said.
Davids from CHAMP said that the announcement would stigmatize gay men.
“I think one of the harms is pointing fingers at gay men instead of pointing resources,” she said. “In the history of the AIDS crisis, we’ve always had a scapegoat.”
Jefferys criticized Ho for not disclosing a business relationship he has with ViroLogic and the fact that his brother is employed there. Ho has received ViroLogic stock options during his time with the company, according to Petropoulos. With the company stock trading at around $2.50 a share, Ho will not reap great rewards from that relationship.
“I think it’s safe to say that none of our scientific advisory board members are getting rich,” Petropoulos said.
Jefferys said that Ho is chairing the Conference on Retroviruses and Opportunistic Infections, which opens on February 22 in Boston. The announcement last week, he suggested, may be an effort to promote his work in advance of the conference.
“There is a suspicion that there is a desire to generate publicity,” Jefferys said. “Obviously, until all the data is released in a journal we can’t know for sure. It’s always problematic to do science by press release.”