New York City case of multidrug-resistant, rapid AIDS progression baffling

Health officials continue investigation

HIV physicians and public health officials say the recent discovery of a man in his mid-40s with both rapidly progressing AIDS and a highly resistant strain could portend an ominous turn in the epidemic, particularly in light of evidence that the transmission of antiretroviral resistant HIV is increasing in some cities.

"This type of case should serve as a wake-up call that HIV remains a formidable adversary despite the fact that we’re living in an era where there are multiple effective antiretroviral drugs," explains Ron Valdiserri, MD, MPH, deputy director of the National Center for HIV, STD, and TB Prevention at the CDC.

The New York City Department of Health and Mental Hygiene issued a medical alert Feb. 11, 2005, to notify physicians that a New York City man had been diagnosed in January with primary HIV infection with HIV-1 that was resistant to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). The medical alert also noted the increase in transmission of resistant virus in New York City.1

In New York City, the percentage of HIV patients who have resistance to two or more classes of antiretroviral drugs increased from 2.6% to 9.8% between 1995-1998 and 2003-2004.1

With the possible exception of efavirenz (Sustiva) and the fusion class drug T-20 (Fuzeon), genotypic and phenotypic testing demonstrated complete antiretroviral drug resistance.1 Less than 1% of people newly diagnosed with HIV are resistant to three or more classes of drugs, Valdiserri says.

The case involved a man who has sex with men (MSM) who tested negative for HIV in May 2003, and then tested positive on Dec. 16, 2004. He reported symptoms of acute retroviral syndrome during early November 2004, and he said he used crystal methamphetamine while engaging in unprotected insertive and receptive anal intercourse with multiple partners, including those met through the Internet, in mid-October 2004.1

What made this case extraordinary was that it combined in one man the rare event of newly acquired, highly resistant HIV and rapid progression to AIDS, HIV experts say.

"It could be a perfect storm of two bad things happening at the same time," says Jay F. Dobkin, MD, associate professor of clinical medicine at Columbia University Medical Center. The key question is whether there is something about that particular strain that leads to more rapid progression or whether the rate of progression has more to do with that particular HIV patient, he says.

The man’s virus appeared to be dual-tropic, meaning his virus was able to use both CCR5 and CXCR4 as coreceptors, which HIV experts say may be a factor in why his disease has progressed so rapidly.1

"Most often, we don’t see dual-tropism until later stages of disease," says James Braun, DO, president of New York City-based Physicians’ Research Network Inc.

"This infection is not only rapidly progressive, but also it’s potentially untreatable — not a good combination," he says. "From a public health standpoint, it’s extremely important to make people aware of this because you don’t want to wait and see an enormous number of people who have been infected with it."

New York City officials defined the man’s disease as AIDS in January 2005 after a physical exam showed that he had lost weight, continued to have fatigue and malaise, and had a CD4 cell count of less than 100 cells, along with an elevated viral load.1

"The most intriguing debate about this case is whether this [strain] really is as aggressive as it seems," Dobkin explains. "The man’s T cell count could rebound to a more normal level. We don’t know exactly how long it’s been going on, so there’s a remote possibility that after the dust settles, his disease won’t look as bad as it does now.’

There’s also a possibility that even if this man has transmitted multidrug resistance to other people, his rapid progression to AIDS is unique to his own situation.

For example, the man’s immune system could be affected by his drug use or other factors, Braun says. But if the man’s virus is transmissible and has a similar affect on other people, it could have a devastating impact on communities at risk for HIV, he continues. "Personally, I hope this is an isolated case, but if it’s not an isolated case, then greater action needs to be taken toward early diagnosis, and there needs to be a great deal more effort at all levels in diagnosing primary HIV infection," Braun adds.

While it’s generally accepted that it takes 10 to 11 years for the typical HIV infection to progress to AIDS, there have been people who progressed much faster, and others who progressed more slowly since the epidemic began, Dobkin says.

"There’s always a question about why some people handle the virus so well and others so poorly, and the great bulk of data say it has to be with the host and not the virus. So even if this man transmits it to others, most of them won’t have such an aggressive disease."

For this particular man, the news is grim because it’s unlikely he’ll survive long enough to benefit from treatment with new classes of HIV drugs, he adds.

While he could be treated with the one available fusion inhibitor for a while, the response likely will be transient, eventually putting him back to where he began, Dobkin notes.

The CDC and New York City public health officials say this case is yet another sign that unsafe sex practices, coupled with substance use, are on the rise in the MSM community. Other indications include rising syphilis rates and recent reports of lymphogranuloma venereum (LGV) in HIV-positive MSM.1

"It is significant that this individual had problems with crystal methamphetamine use, and much of the unsafe sex took place under the influence of crystal meth use," Valdiserri says.

"Crystal meth use has been associated with higher STDs, and some jurisdictions have observed what they believe to be increases in HIV transmission associated with crystal meth use." The fact that unsafe sex practices may be on the rise and that drug use may be associated with unsafe sex should affect prevention efforts, he says. "An important national message is that HIV prevention efforts have to keep pace with emerging challenges. We really need to be careful not to grow complacent about HIV."

This one case, which has made it to the front pages of newspapers across the country, serves as a reminder to the general public that people engaging in high-risk activities are in real danger, Dobkin notes.

Valdiserri and other health officials also point to the need for a public health investment in better HIV surveillance systems and data about drug resistance. "We’re going to have to invest in systems that monitor drug resistance," Valdiserri says.

Clinicians in the New York City area are asked by the city health department to test for drug resistance in all people with newly diagnosed HIV and to report to the city’s Bureau of HIV/AIDS Prevention and Control any cases in which a patient is suspected to be resistant to three classes of HIV antiretrovirals.1

As of mid-February, New York City and CDC health officials were continuing to investigate the case to identify people who might have been exposed to the highly resistant strain and to see if they were in danger of a fast progression to AIDS. A more detailed report is expected later this year.

Reference

1. New York City Department of Health and Mental Hygiene. DOHMH Alert #7: Primary 3-Drug-Class-Resistant HIV-1 Infection with Rapid CD4+ T Cell Depletion and Progression to AIDS in a New York City Man Who Has Sex with Men. Feb. 11, 2005.